bluuebunny/crossref_metadata_2025 huggingface dataset:
Denervation Resulting in Dento-Alveolar Ankylosis Associated with Decreased Malassez Epithelium
Authors: Fujiyama K. , Yamashiro T. , Fukunaga T. , Balam T.A. , Zheng L. , Takano-Yamamoto T.
Published: January 2009

Inferior alveolar nerve denervation causes appreciable decreases in the distribution of epithelial rests of Malassez. To explore roles of the Malassez epithelium, we attempted to evaluate possible changes in dento-alveolar tissues surrounding this epithelium by experimental denervation. We found that denervation led to dento-alveolar ankylosis with a decrease in the width of the periodontal spaces. Interestingly, with regeneration of the Malassez epithelium 10 weeks after the denervation, the periodontal space width showed a correspondingly significant increase. These findings suggest that the Malassez epithelium may be involved in the maintenance of periodontal space and that sensory innervation might be indirectly associated with it. In addition, it is of interest that denervation activated root resorption of the coronal root surface and that the consequently resorbed lacunae were repaired by cellular cementum. It is suggested that Malassez epithelium may negatively regulate root resorption and induce acellular cementum formation.
An Eight-year Follow-up to a Randomized Clinical Trial of Participant Satisfaction with Three Types of Mandibular Implant-retained Overdentures
Authors: Timmerman R. , Stoker G.T. , Wismeijer D. , Oosterveld P. , Vermeeren J.I.J.F. , van Waas M.A.J.
Published: January 2009

Studies have shown that mandibular implant overdentures significantly increase satisfaction and quality of life of edentulous elders. Improved chewing ability appears to have a positive impact on nutritional state. Therefore, it is important to determine the best design of this prosthesis over the long term. In this randomized controlled trial, three groups of edentulous participants with atrophic mandibles wore 3 types of implant overdentures. During an eight-year follow-up, only seven of the 110 participants had dropped out of this study. Almost all participants were still satisfied with their overdentures. Participant satisfaction concerning retention and stability of the mandibular overdenture had decreased significantly in the two-implant ball attachment group, whereas the opinion of participants in the single- and triple-bar groups was still at the same level. The long-term results suggest that a mandibular overdenture retained by 2 implants with a single bar may be the best treatment strategy for edentulous people with atrophic ridges.
Prevalence of Human Herpesvirus-8 Salivary Shedding in HIV Increases with CD4 Count
Authors: Gandhi M. , Koelle D.M. , Ameli N. , Bacchetti P. , Greenspan J.S. , Navazesh M. , Anastos K. , Greenblatt R.M.
Published: January 2009

Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi’s sarcoma (KS), which occurs in epidemic form in human immunodeficiency virus(HIV)-infected individuals. Saliva is the only mucosal fluid in which infectious HHV-8 has been identified, although factors associated with HHV-8 salivary shedding remain unclear. Our study performed PCR analysis for HHV-8 DNA in saliva (and other body fluids) in 66 HIV- and HHV-8-co-infected women without KS so that we could examine predictors for HHV-8 DNA detection. CD4 count was the most significant predictor of HHV-8 salivary shedding, with increased prevalence of HHV-8 salivary DNA at higher CD4 counts. The odds of salivary HHV8 shedding at CD4 counts > = 350 cells/μL was 63 times the odds of shedding at CD4 < 350 (95%CI, 1.3–3078), with an increase in effect size when the analysis was restricted to those with a CD4 nadir > 200. Analysis of these data suggests an increased potential for HHV-8 transmission early in HIV infection, with implications for HHV-8 prevention.
Apoptotic Effects of LPS on Fibroblasts are Indirectly Mediated through TNFR1
Authors: Alikhani M. , Alikhani Z. , Graves D.T.
Published: January 2009

During periods of periodontal attachment loss, one of the most significant cellular changes is a decrease in the number of fibroblasts. We previously demonstrated that LPS induces apoptosis of fibroblastic cells in vivo, largely through TNF-α. We conducted in vivo experiments by subcutaneous inoculation of LPS in wild-type, TNFR1−/−R2−/−, TNFR1−/−, and TNFR2−/− mice to identify which TNF receptors are involved and the specific caspase pathway activated. LPS stimulated apoptosis through TNFR1 but not TNFR2, which was accompanied by the induced expression of 12 apoptotic genes. Fluorometric studies demonstrated that LPS in vivo significantly increased caspase-8 and caspase-3 activity, which was also dependent on TNF receptor signaling. By the use of specific caspase inhibitors, caspases-3 and -8 were shown to play an important role in LPS-induced apoptosis in vivo. Thus, LPS acts through TNFR1 to modulate the expression of apoptotic genes and activate caspases-3 and -8.
Semaphorin Profiling of Periodontal Fibroblasts and Osteoblasts
Authors: Lallier T.E.
Published: January 2009

Cells of the periodontal attachment (cementoblasts, osteoblasts, and periodontal ligament fibroblasts) are descended from a common progenitor (the cranial neural crest). During their differentiation into different cell types, these cells separate from one another to form a laminated structure. Semaphorins (and their neuropilins and plexin receptors) act as cell guidance molecules for other neural crest derivatives. It is predicted that the differential expression of these molecules will correlate with the ability of these cells to segregate. It is demonstrated that human pre-osteoblasts segregate from PDL and gingival fibroblasts in culture. In addition, these cells express different semaphorins and plexins. Semaphorins 3D and 7A were expressed preferentially in dermal fibroblasts, while semaphorin 6B was selectively expressed by pre-osteoblasts. Semaphorins 3B, 4C, 5B, and 6C and plexins B1 and C1 were expressed in reduced levels in pre-osteoblasts. Analysis of the data suggests that differential expression of semaphorins and plexins may be involved in regulating cell-sorting in the formation and regeneration of the periodontal attachment structure. Abbreviations: Periodontal Ligament (PDL), Reverse Transcriptase Polymerase Chain-reaction (RT-PCR).
Effects of Cyclosporin-A-induced Immunosuppression on Periapical Lesions in Rats
Authors: Kawahara T. , Murakami S. , Noiri Y. , Ehara A. , Takemura N. , Furukawa S. , Ebisu S.
Published: January 2009

Cyclosporin A (CsA) might induce immune response alterations in periapical lesions and modify bone remodeling. This study determined the changes that occur in the periapical lesions of rats during CsA administration and after CsA withdrawal. After the induction of periapical lesions, the animals were treated with CsA (0–20 mg/kg/day) for 4 wks. Lesion volumes were measured by computed tomography. Histological observations and immunohistochemical evaluations were performed with anti-CD3 and anti-CD25 antibodies. CsA administration reduced lesion volumes, and the lesions significantly expanded after CsA withdrawal. CsA inhibited the proliferation and activation of T-cells at lesion sites. The effects of CsA on T-cells were dose-dependent up to 10 mg/kg/day, after which no significant difference was evident. These results suggest that CsA inhibits periapical destruction by interfering with T-cell function in periapical lesions.
Methods for Enhancing the Efficiency of Dental/Oral Health Clinical Trials: Current Status, Future Possibilities
Authors: Barnett M.L. , Pihlstrom B.L.
Published: January 2009

BACKGROUND

In recent years, there has been an increasing demand for clinical trials to study oral, dental, and craniofacial diseases and conditions. This has resulted from such factors as the increasing pace of discoveries requiring translational research to develop them for clinical use, FDA requirements for product approval, a need for additional data to support evidence-based dental practice, and the expansion of the NIDCR’s clinical research programs. The complexity, size, and duration of clinical trials often make them quite costly to conduct, and may impede the development of novel diagnostic, preventive, and therapeutic methods that could have a significant impact on clinical practice and inform public health policy. Recent advances in such areas as genomics and proteomics, coupled with the development of new technologies, have expanded our knowledge of the etiology and pathogenesis of disease and, from this, have provided new insights into the design and conduct of clinical trials. The workshop, “Methods for Enhancing the Efficiency of Dental/Oral Health Clinical Trials: Current Status, Future Possibilities”, held on May 6–7, 2004, considered a variety of ways in which these insights are being, or have the potential to be, applied to clinical trials so as to enhance their efficiency and, hence, their cost-effectiveness, without diminishing the quality of information produced. The focus of this workshop was to assess the state of the science and identify research needs for the use of biomarkers, surrogate endpoints, and new technologies in oral disease clinical trials. Examples of ways in which clinical trials of other diseases have benefited from the use of new methods and technologies and FDA considerations were also discussed.
Chewing-side Preference is Involved in Differential Cortical Activation Patterns during Tongue Movements after Bilateral Gum-chewing: a Functional Magnetic Resonance Imaging Study
Authors: Shinagawa H. , Ono T. , Honda E. , Sasaki T. , Taira M. , Iriki A. , Kuroda T. , Ohyama K.
Published: January 2009

Contralateral dominance in the activation of the primary sensorimotor cortex (S1/M1) during tongue movements (TMs) has been shown to be associated with a chewing-side preference (CSP). However, little is known about its interaction with chewing-related cortical activation. Functional magnetic resonance imaging was performed before and after gum-chewing in six subjects who exhibited a left CSP to determine the relationship between the CSP and activation patterns in the S1/M1 during TMs. Before the subjects chewed the gum, activation foci were found in the bilateral S1/M1. In the left hemisphere, both signal intensity and the area of activation significantly increased during TMs within 10 min after subjects chewed gum. Moreover, this augmented activation significantly decreased within 20 min during tongue protrusion and leftward movement. In the right hemisphere, there were no marked changes during TMs. These results suggest that bilateral gum-chewing enhances activation of the S1/M1 ipsilateral to the CSP during TMs.
Modeling Multivariate Binary Responses with Multiple Levels of Nesting Based on Alternating Logistic Regressions: an Application to Caries Aggregation
Authors: Ananth C.V. , Kantor M.L.
Published: January 2009

Clustered binary responses are commonly encountered in dental research. Data analysis may include modeling both the marginal response probabilities ( i.e., risk) and the dependence structure between pairs of responses ( i.e., aggregation). While second-order generalized estimating equations (GEE2) is a well-known approach for such data, alternating logistic regressions (ALR) is a computationally efficient alternative method, especially for large clusters. We illustrate ALR with an application to caries aggregation using a dataset with 3 levels of nesting: tooth surfaces within an interproximal (IP) region, IP regions within a jaw, and jaws within a subject. Caries lesions appear to aggregate strongly within subjects with a spatially distributed risk. The minimum within-IP-region odds ratio (OR) was 2.25 (95% confidence interval 1.15, 4.41), and the within-IP-region ORs were always greater than the between-IP-region ORs. ALR is a convenient and useful regression technique for explicit modeling of the dependence structure, and may be applicable to other dental research problems involving clustered or nested responses.
Linkage Disequilibrium between MSX1 and Non-syndromic Cleft Lip/Palate in the Chilean Population
Authors: Suazo J. , Santos J.L. , Carreño H. , Jara L. , Blanco R.
Published: January 2009

Non-syndromic cleft lip/palate (NSCLP) is a complex genetic trait. Linkage and association studies have suggested that a clefting locus could be located on chromosome 4p. Sixty Chilean families were recruited for this study; from these, we used unrelated trios to evaluate the possible linkage disequilibrium between MSX1 and NSCLP. An intragenic marker, MSX1-CA, and an extragenic marker, D4S432 at a distance of 0.8 cM from MSX1, were analyzed by means of polymerase chain-reaction with fluorescent-labeled forward primers, followed by electrophoresis on a laser-fluorescent sequencer. We carried out a transmission/disequilibrium test (TDT) for multiple alleles to evaluate the presence of linkage disequilibrium. Results showed a preferential transmission of the 169-bp allele of MSX1 (p = 0.03). Although there was no preferential transmission for the D4S432 marker, the overall extended TDT (ETDT) showed a significant result (p = 0.01). The authors’ findings support the hypothesis of the contribution of MSX1 in the etiology of NSCLP in the Chilean population.
IL-1α Stimulates Cathepsin K Expression in Osteoclasts via the Tyrosine Kinase-NF-κB Pathway
Authors: Kamolmatyakul S. , Chen W. , Yang S. , Abe Y. , Moroi R. , Ashique A.M. , Li Y.-P.
Published: January 2009

Interleukin-1α (IL-1α) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1α up-regulates the expression of cathepsin K protein, a key protease in bone resorption, by five-fold. Northern blot analysis and promoter analysis show that this induction occurs at the transcriptional level, in a dose-responsive and time-dependent manner. No increase in expression occurs in the presence of either pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1α up-regulation may be via the tyrosine kinase-NF-κB pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF-κB, suppress the IL-1α-induced expression of cathepsin K. We therefore conclude that IL-1α up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF-κB pathway.
Deficient Cell Proliferation in Palatal Shelf Mesenchyme of CL/Fr Mouse Embryos
Authors: Sasaki Y. , Tanaka S. , Hamachi T. , Taya Y.
Published: January 2009

How secondary palate formation is affected in the cleft lip genotype remains poorly understood. The purpose of this study was to analyze regional patterns of cell proliferation in CL/Fr mouse embryos with or without cleft lip. Pairs of palatal shelves were dissected at E13.5 from CL/Fr normal embryos (CL/Fr-N), CL/Fr embryos with bilateral cleft lip (CL/Fr-BCL), and a control strain of C57BL embryos (C57BL). The explants were examined histologically after 48 hrs of organ culture. Cell kinetics for proliferation in the palatal shelves was examined at E13.5 by the bromodeoxyuridine method in vivo. The CL/Fr-BCL palates fused as well as the CL/Fr-N palates in vitro. There were inter-group differences in the absolute number of BrdU-positive cells and the ratio of positive/(positive+negative) cells in the palate’s mesenchyme (C57BL > CL/Fr-N > CL/Fr-BCL) and epithelium (C57BL > CL/Fr-N = CL/Fr-BCL). These findings indicate that a cleft palate follows reduced cell proliferation of secondary palatal mesenchyme in CL/Fr mice.
In situ Biofilm Formation by Multi-species Oral Bacteria Under Flowing and Anaerobic Conditions
Authors: Filoche S.K. , Zhu M. , Wu C.D.
Published: January 2009

An understanding of biofilm behavior of periodontopathic bacteria is key to the development of effective oral therapies. We hypothesized that interspecies bacterial aggregates play an important role in anaerobic biofilm establishment and proliferation, and contribute to the survivability of the biofilm against therapeutic agents. The system developed in this study assessed a multi-species ( Streptococcus gordonii, Actinobacillus actinomycetemcomitans, and Fusobacterium nucleatum) biofilm formation under anaerobic and flowing conditions with the use of an in situ image analysis system. The biofilm was comprised of a base film of non-aggregated cells and complex interspecies aggregates that formed in the planktonic phase which rapidly colonized the surface, reaching 58 ± 9% and 65 ± 11.8% coverage by 5 and 24 hrs, respectively. Upon SDS (0.1%) treatment of a 24-hour biofilm, substantial detachment (55 ± 14%, P < 0.05) of the aggregates was observed, while the base film bacteria remained attached but non-viable. Rapid re-establishment of the biofilm occurred via attachment of viable planktonic aggregates.
The Emerging Role of the Insulin-like Growth Factors in Oral Biology
Authors: Werner H. , Katz J.
Published: January 2009

The insulin-like growth factors (IGF) are a family of growth factors, receptors and binding proteins that are involved in numerous growth and differentiation processes, as well as in various pathological conditions. The aim of this review is to summarize data that has been accumulating in recent years linking the IGF system to a number of physiological and pathological oral processes. The IGF system fulfills an important role in growth and development of teeth, mandible, maxillae, and tongue. It has been postulated that IGF-I may be of great value in the treatment of periodontal defects and in tissue healing. Furthermore, IGF-II has been shown to be overexpressed in salivary gland adenomas, suggesting that aberrant IGF signaling may be a key factor in the etiology of oral malignancies. Understanding the role and regulation of IGF system components in salivary glands and other oral structures will be of significant basic and clinical relevance.
A Comprehensive Index for the Modeling of Smoking History in Periodontal Research
Authors: Dietrich Th. , Hoffmann K.
Published: January 2009

Cigarette smoking is both a strong and common risk factor for chronic periodontitis. It is a multi-dimensional exposure that is difficult to model accurately. We propose a new comprehensive smoking index (CSI) that accounts for intensity, duration, and recency of smoking and allows for estimation of the half-life of the smoking effect. Using NHANES III data from 12,623 subjects aged 20+ yrs, we compared the performance of the CSI with that of various conventional approaches using multiple logistic regression models of chronic periodontitis. The estimate of the smoking effect’s half-life was 1.5 yrs (95% CI, 0.5–2.5 yrs). Use of the new index resulted in best model fit and the highest Wald statistic for the smoking effect on chronic periodontitis. The results suggest that use of the CSI may be a more comprehensive, efficient, and parsimonious approach to the modeling of smoking history in periodontal research.
Tobacco-related-compound-induced Nitrosative Stress Injury in the Hamster Cheek Pouch
Authors: Barley R.D.C. , Pollock S. , Shallow M.C. , Peters E. , Lam E.W.N.
Published: January 2009

The nitric oxide radical (•NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the formation of peroxynitrite (ONOO−), the reaction product of •NO and the oxygen radical, superoxide. We hypothesize that tobacco-related compounds are cytotoxic and induce quantifiable DNA single-strand breaks in immortalized hamster cheek pouch (POII) cells, and that an amino acid marker of ONOO− injury, namely, 3-nitrotyrosine (3-NT), is detectable in hamster cheek pouch tissues chronically exposed to these compounds. We observed a dose-dependent decrease in POII cell viability with increasing tobacco-related compound concentrations, as well as a dose-dependent increase in DNA strand breaks. Semi-quantitative immunohistochemistry showed intense 3-NT immunoreactivity in hamster tissues treated with tobacco-related compounds compared with controls (p < 0.005). Our results suggest that tobacco-related compounds, including nicotine, are genotoxic, and that 3-NT is a quantifiable marker of ONOO− damage in intact hamster cheek pouch tissues.
Decreased Mineral Content in MMP-20 Null Mouse Enamel is Prominent During the Maturation Stage
Authors: Bartlett J.D. , Beniash E. , Lee D.H. , Smith C.E.
Published: January 2009

During enamel development, matrix metalloproteinase-20 (MMP-20, enamelysin) is expressed early during the secretory stage as the enamel thickens, and kallikrein-4 (KLK-4, EMSP1) is expressed later during the maturation stage as the enamel hardens. Thus, we investigated whether the physical properties of the secretory-/maturation-stage MMP-20 null enamel were significantly different from those of controls. We demonstrated that although, in relative terms, the weight percent of mature mineral in the MMP-20 null mouse enamel was only 7–16% less than that in controls, overall the enamel mineral was reduced by about 50%, and its hardness was decreased by 37%. Percent mineral content by weight was assessed at 3 different developmental stages. Remarkably, the biggest difference in mineral content between MMP-20 null and controls occurred in the nearly mature enamel, when MMP-20 is normally no longer expressed. This suggests that MMP-20 acts either directly or indirectly to facilitate the removal of maturation-stage enamel proteins.
Progress of Cell Proliferation in Striated Muscle Tissues during Development of the Mouse Tongue
Authors: Nagata J. , Yamane A.
Published: January 2009

The developmental stages of and places for the proliferation of tongue muscle cells have not yet been determined. To determine the stages of and places for proliferation between embryonic day (E) 9 and birth, we analyzed the expression of cyclin D1 mRNA and the immunolocalization for proliferating cell nuclear antigen (PCNA). The ratio of PCNA-positive nuclei to total nuclei (PCNA-labeling index) was obtained in the anterior, middle, and posterior regions. Cyclin D1 mRNA was highly expressed between E11 and E13, but decreased thereafter until birth. The distribution of PCNA-positive cell nuclei was consistent with that of myogenic cells in the occipital somites at E9. The PCNA-labeling index was highest at E11, then decreased until birth without a significant difference among the 3 regions. These findings suggest that some tongue muscle progenitor cells begin proliferation in the occipital somites at E9, and that the proliferation in the whole tongue region occurred most actively between E11 and E13, then decreased until birth without regional differences.
Localization of Porphyromonas gingivalis-carrying Fimbriae in situ in Human Periodontal Pockets
Authors: Noiri Y. , Li L. , Yoshimura F. , Ebisu S.
Published: January 2009

Fimbriae, which are involved in adherence, constitute an important pathogenic factor of Porphyromonas gingivalis. In vivo, however, the distribution of P. gingivalis-carrying fimbriae is unknown. The localization of P. gingivalis-carrying fimbriae was examined in situ. From 19 patients with severe periodontitis and P. gingivalis, we obtained 20 teeth with periodontal tissue attached, with and without immunolocalized fimbriae. Eleven teeth were subjected to light microscopy, 9 to electron microscopy. In 6 of the 11 samples examined, we detected positive reactions with an anti- P. gingivalis-fimbriae serum, located in the cementum-attached plaque area in the deep pocket zones. In the so-called ‘plaque-free zones’, P. gingivalis-carrying fimbriae were immunocytochemically observed to reside in contact with the dental cuticle in 6 of the 9 samples examined. These findings suggest that P. gingivalis-carrying fimbriae are strongly related to adherence to the root surface at the bottoms of human periodontal pockets.
Dimensions of Oral-health-related Quality of Life
Authors: John M.T. , Hujoel P. , Miglioretti D.L. , LeResche L. , Koepsell T.D. , Micheelis W.
Published: January 2009

Oral-health-related quality of life (OHRQoL) is expected to have multiple dimensions. It was the aim of this study to investigate the dimensional structure of OHRQoL measured by the Oral Health Impact Profile (German version) (OHIP-G) and to derive a summary score for the instrument. Subjects (N = 2050; age, 16–79 yrs) came from a national survey. We used rotated principal-components analysis to derive a summary score and to explore the dimensional structure of OHIP-G. The first principal component explained 50% of the variance in the data. The sum of OHIP-G item responses was highly associated with the first principal component (r = 0.99). This simple but informative OHIP-G summary score may indicate that simple sums are also potentially useful scores for other OHRQoL instruments. Four dimensions (psychosocial impact, orofacial pain, oral functions, appearance) were found. These OHIP-G dimensions may serve as a parsimonious set of OHRQoL dimensions in general.
Information and Participation Preferences of Dental Patients
Authors: Schouten B.C. , Eijkman M.A.J. , Hoogstraten J.
Published: January 2009

Dutch dentists have a moral and legal obligation to inform their patients and involve them in the decision-making process. It is unclear, though, to what extent patients prefer information and involvement in decision-making. Therefore, the aim of this study was to determine levels of preference for information and participation in decision-making among emergency patients (n = 96) and regular patients (n = 245). It was hypothesized that female gender, higher education, younger age, and a monitoring coping style are positively associated with higher preferences for information and participation. The results demonstrated that emergency and regular patients have high preferences for information, but that their preferences for actual involvement are significantly lower. Only weak associations were found between the antecedent variables and patients’ preferences. It is concluded that, in the study of the etiology of patients’ preferences for information and participation, future research should incorporate factors such as dental anxiety and seriousness of the dental condition.
The Future of Web-based Clinical Research in Dentistry
Authors: Marks R.G.
Published: January 2009

Clinical research is a growing industry in dentistry, requiring more efficient methods for research conduct. The Internet provides an opportunity for investigators to expand, enhance, and potentially redefine the way they conduct clinical research. A prime area for improved research is in clinical trials processes, due to their current high cost and inefficiencies. The Web offers the advantages of both centralization of information and coordination of multiple clinical trials processes. The result is improvements for the investigator sites, the sponsor, and subject safety. Observational studies also provide the opportunity for investigators to collect greater amounts of information in a more realistic dental environment. The Internet offers investigators the opportunity to collect outcomes information from sources worldwide, and more efficiently, accurately, and quickly, providing new valuable research answers. The tremendous explosion of genetic and gene therapy research will substantially increase the need for research methods that can manage the vast amount of complex new data, depending on the Internet to manage these research needs. The Internet holds promise for improving dental clinical research through its gains in efficiency, accuracy, and safety.
What Constitutes Dental Caries? Histopathology of Carious Enamel and Dentin Related to the Action of Cariogenic Biofilms
Authors: Kidd E.A.M. , Fejerskov O.
Published: January 2009

Substantial pH fluctuations within the biofilm on the tooth surface are a ubiquitous and natural phenomenon, taking place at any time during the day and night. The result may be recordable in the dental tissues at only a chemical and/or ultrastructural level (subclinical level). Alternatively, a net loss of mineral leading to dissolution of dental hard tissues may result in a caries lesion that can be seen clinically. Thus, the appearance of the lesion may vary from an initial loss of mineral, seen only in the very surface layers at the ultrastructural level, to total tooth destruction. Regular removal of the biofilm, preferably with a toothpaste containing fluoride, delays or even arrests lesion progression. This can occur at any stage of lesion progression, because it is the biofilm at the tooth or cavity surface that drives the caries process. Active enamel lesions involve surface erosion and subsurface porosity. Inactive or arrested lesions have an abraded surface, but subsurface mineral loss remains, and a true subsurface remineralization is rarely achievable, because the surface zone acts as a diffusion barrier. The dentin reacts to the stimulus in the biofilm by tubular sclerosis and reactionary dentin.
Bitewing and Digital Bitewing Radiography for Detection of Caries Lesions
Authors: Wenzel A.
Published: January 2009

When radiography is applied in the clinic for caries detection, the recommended technique is bitewing projection (Gröndahl, 1994). This technique was introduced by Raper (1925) and has continued with only minor alterations. The aims of this report are to provide evidence for (1) optimal bitewing recording for individual examinations and clinical trials, (2) advantages and disadvantages of digital receptors for bitewing examinations, (3) the diagnostic outcomes and limitations of bitewing radiography, and (4) computerautomated detection of caries.
Current Issues in Clinical Equivalence Trials
Authors: Blackwelder W.C.
Published: January 2009

A clinical trial designed to show that an experimental treatment E is similar to a control treatment S in a specified direction is a one-sided equivalence or similarity trial—in the terminology of the International Conference on Harmonisation, a non-inferiority trial (ICH, 1998). We design such a study to show that E is not worse than S (often an accepted or standard treatment) by as much as a pre-specified margin θ0. The quantity θ0 can be either a difference or ratio of an appropriate outcome in individuals treated with E and S. A critical issue is whether one can conclude from a non-inferiority trial that E is effective. Closely related is an appropriate choice of θ0, which should be substantially less than the estimated effect of S if available from previous studies; θ0 should also be acceptable to clinicians, either because of advantages of E or because a difference or ratio less than θ0 is considered unimportant clinically. Another possible approach for showing that E is effective is to estimate its effect compared with placebo from historical data. If previous studies that consistently show an effect of S are not available, alternative study designs should be considered. Findings of superiority or non-inferiority of E, when the study was planned to show the other, are possible and may be supportable. A finding that E is at the same time statistically significantly worse than S and “non-inferior” to S should not be a problem, if the criterion θ0 is appropriate and this possibility was considered in the protocol. Various sorts of non-adherence may make treatments appear similar, even if they are not. In particular, random non-adherence of study participants to the assigned treatment regimen may cause an intention-to-treat analysis to give a misleading result of similarity. Thus, maintaining a high degree of adherence to protocol is especially important in an equivalence or non-inferiority trial. Interim analysis does not present statistical problems in these trials; early stopping may not be wise in many cases, however, because strong interim evidence for non-inferiority may actually be an indicator that E is superior to S.
ABO Blood-group Antigens in Oral Cancer
Authors: Dabelsteen E. , Gao S.
Published: January 2009

Tumor progression is often associated with altered glycosylation of the cell-surface proteins and lipids. The peripheral part of these cell-surface glycoconjugates often carries carbohydrate structures related to the ABO and Lewis blood-group antigens. The expression of histo-blood-group antigens in normal human tissues is dependent on the type of differentiation of the epithelium. In most human carcinomas, including oral carcinoma, a significant event is decreased expression of histo-blood-group antigens A and B. The mechanisms of aberrant expression of blood-group antigens are not clear in all cases. A relative down-regulation of the glycosyltransferase that is involved in the biosynthesis of A and B antigens is seen in oral carcinomas in association with tumor development. The events leading to loss of A transferase activity are related, in some instances, to loss of heterozygosity (LOH) involving chromosome 9q34, which is the locus for the ABO gene, and in other cases, to a hypermethylation of the ABO gene promoter. The fact that hypermethylation targets the ABO locus, but not surrounding genes, suggests that the hypermethylation is a specific tumor-related event. However, since not all situations with lack of expression of A/B antigens can be explained by LOH or hypermethylation, other regulatory factors outside the ABO promoter may be functional in transcriptional regulation of the ABO gene. Altered blood group antigens in malignant oral tissues may indicate increased cell migration. This hypothesis is supported by studies showing that normal migrating oral epithelial cells like malignant cells show lack of expression of A/B antigens, and by studies that target ABH antigens to key receptors controlling adhesion and motility, such as integrins, cadherins, and CD-44.
Zinc Gluconate in the Treatment of Dysgeusia—a Randomized Clinical Trial
Authors: Heckmann S.M. , Hujoel P. , Habiger S. , Friess W. , Wichmann M. , Heckmann J.G. , Hummel T.
Published: January 2009

In the treatment of dysgeusia, the use of zinc has been frequently tried, with equivocal results. The aim of the present randomized clinical trial, which involved a sufficiently large sample, was therefore to determine the efficacy of zinc treatment. Fifty patients with idiopathic dysgeusia were carefully selected. Zinc gluconate (140 mg/day; n = 26) or placebo (lactose; n = 24) was randomly assigned to the patients. The patients on zinc improved in terms of gustatory function (p < 0.001) and rated the dysgeusia as being less severe (p < 0.05). Similarly, signs of depression in the zinc group were less severe (Beck Depression Inventory, p < 0.05; mood scale, p < 0.05). With the exception of the salivary calcium level, which was higher in the zinc patients (p < 0.05), no other significant group differences were found. In conclusion, zinc appears to improve general gustatory function and, consequently, general mood scores in dysgeusia patients.
Frailty Approach for the Analysis of Clustered Failure Time Observations in Dental Research
Authors: Chuang S.K. , Cai T. , Douglass C.W. , Wei L.J. , Dodson T.B.
Published: January 2009

Because dental implant failure patterns tend to cluster within subjects, we hypothesized that the risk of implant failure varies among subjects. To address this hypothesis in the setting of clustered, correlated observations, we considered a retrospective cohort study where we identified a cohort having at least one implant placed. The cohort was composed of 677 patients who had 2349 implants placed. To test the hypothesis, we applied an innovative analytic method, i.e., the Cox proportional hazards model with frailty, to account for correlation within subjects and the heterogeneity of risk, i.e., frailty, among subjects for implant failure. Consistent with our hypothesis, risk for implant failure among subjects varied to a statistically significantly degree (p = 0.041). In addition, the risk for implant failure is significantly associated with several factors, including tobacco use, implant length, immediate implant placement, staging, well size, and proximity of adjacent implants or teeth.
Identification of Markers of the Midface
Authors: Gong S.-G. , Gong T.-W. , Shum L.
Published: January 2009

Currently, much remains unknown of the genes that mediate the biological events during growth and fusion of the midfacial region, and the possible pathways through which these genes function. We took advantage of high-throughput microarray analysis to search for genes that may play a critical role in the growth and fusion of the midfacial region to become the primary palate. We identified several genes that were potentially expressed at different levels between tail somite (TS) 6-8 (pre-fusion) and TS 12-14 (fusion) in the 3 midfacial processes. Expression of 4 of these genes ( Tbx14/15, Dickkopf-1, Fibroblast Growth Factor 8, and Keratin-18) was further verified by reverse-transcription/quantitative PCR and in situ hybridization at the 2 stages of midfacial development. With the identification of these genes, and possibly others, functional analyses can be conducted to improve our understanding of the mechanisms and pathways by which the midface forms.
Macrophages and Mast Cells Control the Neutrophil Migration Induced by Dentin Proteins
Authors: Silva T.A. , Lara V.S. , Silva J.S. , Oliveira S.H.P. , Butler W.T. , Cunha F.Q.
Published: January 2009

Dentin sialoprotein (DSP) and dentin phosphoprotein (DPP), the major dentin proteins, have been shown to induce neutrophil migration through release of IL-1β, TNF-α, MIP-2, and KC. However, the sources of these mediators were not determined. Here, the roles of macrophages and mast cells (MC) in dentin-induced neutrophil accumulation were investigated. Peritoneal MC depletion or the enhancement of macrophage population increased DSP- and DPP-induced neutrophil extravasation. Moreover, supernatants from DSP- and DPP-stimulated macrophages caused neutrophil migration. The release of neutrophil chemotactic factor by macrophages was inhibited by dexamethasone or the supernatant of DSP-treated MC. Consistently, dexamethasone and the MC supernatant inhibited the production of IL-1β, TNF-α, and MIP-2 by macrophages. This inhibitory activity of the DSP-stimulated MC was neutralized by anti-IL-4 and anti-IL-10 antibodies. These results indicate that dentin induces the release of the neutrophil chemotactic substance(s) by macrophages, which are down-modulated by MC-derived IL-4 and IL-10.
Hyper-expression of Osteocalcin mRNA in Odontoblasts of Hyp Mice
Authors: Onishi T. , Ogawa T. , Hayashibara T. , Hoshino T. , Okawa R. , Ooshima T.
Published: January 2009

The Hyp mouse is a murine homologue of human X-linked hypophosphatemia that displays hypo-mineralization in bone and dentin. In this study, we tested the hypothesis that the defect in Hyp mice leads to alterations in the expression of dentin matrix proteins that may be associated with the hypo-mineralization changes in the tissues. Quantitative RT-PCR analyses showed that expression of the osteocalcin gene in Hyp mice tooth germ samples was significantly higher than in wild-type mice, whereas the gene expressions of osteonectin, osteopontn, dentin matrix protein 1, and type I collagen in both types of mice were similar. Further, cultured Hyp mice tooth germ samples exhibited a higher expression of the osteocalcin gene than did those from wild-type mice, which was in accord with the results of our in vivo analysis. These findings suggest that osteocalcin mRNA is highly expressed in Hyp mice odontoblasts and may be associated with dentin hypo-mineralization.
Porcine Amelogenin is Expressed from the X and Y Chromosomes
Authors: Ikawa T. , Kakegawa A. , Nagano T. , Ando H. , Yamakoshi Y. , Tanabe T. , Simmer J.P. , Hu C.-C. , Fukae M. , Oida S.
Published: January 2009

Amelogenin is the major enamel matrix component in developing teeth. In eutherian mammals, amelogenin is expressed from the X chromosome only, or from both the X and Y chromosomes. Two classes of porcine amelogenin cDNA clones have been characterized, but the chromosomal localization of the gene(s) encoding them is unknown. To determine if there are sex-based differences in the expression of porcine amelogenin, we paired PCR primers for exons 1a, 1b, 7a, and 7b, and amplified enamel organ-derived cDNA separately from porcine males and females. The results show that exons 1a/2a and 7a are always together and can be amplified from both males (XY) and females (XX). Exons 1b/2b and 7b are also always paired, but can be amplified only from females. We conclude that porcine amelogenin is expressed from separate genes on the X and Y chromosomes, and not, as previously proposed, from a single gene with two promoters.
Behçet’s Disease: A Review
Authors: Al-Otaibi L.M. , Porter S.R. , Poate T.W.J.
Published: January 2009

Behçet’s disease (BD) is a multi-system inflammatory disorder dominated clinically by recurrent oral and genital ulceration, uveitis, and erythema nodosum. Behçet’s disease runs a chronic course, with unpredictable exacerbations and remissions whose frequency and severity may diminish with time. Behçet’s disease typically arises in young adults, although childhood-onset BD has also been reported. The disease can affect both genders and has a worldwide distribution, although it is more prevalent in countries of the ancient Silk Route. The cause of BD remains unknown, although an autoimmune reaction triggered by an infectious agent in a genetically predisposed individual has been suggested. The treatment of BD is symptomatic and empirical, but generally specific to the clinical features of each patient. The majority of affected individuals do not have life-threatening disease, although mortality can be associated with vascular-thrombotic and neurological disease.
Increased Apoptosis during Morphogenesis of the Lower Cheek Teeth in Tabby/EDA Mice
Authors: Boran T. , Lesot H. , Peterka M. , Peterkova R.
Published: January 2009

In wild-type (WT) mice, epithelial apoptosis is involved in reducing the embryonic tooth number and the mesial delimitation of the first molar. We investigated whether apoptosis could also be involved in the reduction of tooth number and the determination of anomalous tooth boundaries in tabby (Ta)/EDA mice. Using serial histological sections and computer-aided 3D reconstructions, we investigated epithelial apoptosis in the lower cheek dentition at embryonic days 14.5–17.5. In comparison with WT mice, apoptosis was increased mainly mesially in Ta dental epithelium from day 15.5. This apoptosis showed a similar mesio-distal extent in all 5 morphotypes (Ia,b,c and IIa,b) of Ta dentition and eliminated the first cheek tooth in morphotypes IIa,b. Apoptosis did not appear to play any causal role in positioning inter-dental gaps. Analysis of the present data suggests that the increased apoptosis in Ta mice is a consequence of impaired tooth development caused by a defect in segmentation of dental epithelium.
Influence of Bitter Taste on Mastication Pattern
Authors: Neyraud E. , Peyron M.A. , Vieira C. , Dransfield E.
Published: January 2009

Mastication is a rhythmic activity that can be modified by peripheral information generated in the mouth. To study whether taste cognition could influence the way in which a food is broken down in the mouth, subjects masticated firm, sugar-based gelatine gels with differing concentrations of quinine, up to 1500 μmol/kg, while electromyography (EMG) of masticatory muscles was recorded. Taste intensity and composition of saliva were measured. With increasing quinine concentration, the average number of chews for nine subjects decreased from 30 to 22, and their average clearance time increased from 7 to 14 sec. Quinine concentration had no effect on chewing frequency (1.3 Hz) or on the rate of salivation (5.5 g/min). Bitterness increased, while acceptability and sweetness decreased, with increasing concentration of quinine in the gel and in saliva. Taste cognition could therefore modify food breakdown in the mouth.
Genome-wide Linkage Analysis of Mandibular Prognathism in Korean and Japanese Patients
Authors: Yamaguchi T. , Park S.B. , Narita A. , Maki K. , Inoue I.
Published: January 2009

The existence of familial aggregation of mandibular prognathism (MP) suggests that genetic components play an important role in its etiology. In this study, a genome-wide linkage analysis to identify loci susceptible to MP was conducted with 90 affected sibling-pairs in 42 families, comprised of 40 Korean sibling-pairs and 50 Japanese sibling-pairs. Two non-parametric linkage analyses, GENEHUNTER-PLUS and SIBPAL, were applied and detected nominal statistical significance of linkage to MP at chromosomes 1p36, 6q25, and 19p13.2. The best evidence of linkage was detected near D1S234 (maximum Zlr = 2.51, P = 0.0012). In addition, evidence of linkage was observed near D6S305 (maximum Zlr = 2.23, P = 0.025) and D19S884 (maximum Zlr = 1.93, P = 0.0089). Identification of the susceptible genes in the linkage regions will pave the way for insights into the molecular pathways that cause MP, especially overgrowth of the mandible, and may lead to the development of novel therapeutic tools.
Distinct Patterns of Angiogenesis in Oral and Skin Wounds
Authors: Szpaderska A.M. , Walsh C.G. , Steinberg M.J. , DiPietro L.A.
Published: January 2009

Clinical observation suggests that oral mucosal wounds heal faster than skin; however, little is known about the site-specific differences. Since fetal skin wounds heal rapidly, but are less vascular than adult wounds, we hypothesized that less robust wound angiogenesis might be observed in healing oral mucosa. This study investigated angiogenesis in equivalent-size oral and skin murine wounds. Change in wound bed vascularity was significantly lower in oral wounds than in skin. Also, vascular endothelial growth factor (VEGF) levels were less in oral than cutaneous wounds. Because keratinocytes are a prominent source of VEGF in wounds, we compared VEGF production by oral and epidermal keratinocytes in vitro. Significantly higher levels of VEGF protein and mRNA were observed in epidermal keratinocytes than in oral keratinocytes after 18 hrs of hypoxia. This study demonstrates distinct angiogenesis patterns in oral and skin wounds and intrinsic site-specific differences in VEGF production by keratinocytes.
Localization of am3 using EL Congenic Mouse Strains
Authors: Shimizu T. , Han J. , Asada Y. , Okamoto H. , Maeda T.
Published: January 2009

EL/Sea mice have 100% incidence of the absence of third molars (M3). Our previous linkage analysis using EL/Sea and MSM/Msf mouse strains provides statistical evidence of a major locus for the absence of M3, designated am3, of EL/Sea at the middle region of chromosome 3. To obtain independent evidence for linkage and more precisely determine the location of the am3 locus, we generated EL/Sea congenic strains for am3 in which the restricted interval of chromosome 3 of EL/Sea was replaced by an MSM/Msf-derived homologue. EL/Sea congenic mice that were either heterozygous or homozygous for the MSM/Msf-derived interval exhibited a significant decrease in the incidence of the absence of third molars, confirming previous genome scan results. These results confine the am3 locus to an approximately 4.4-cM region, and demonstrate that other unmapped genes are also involved in the absence of M3 in EL/Sea mice.
Ultrastructural Correlates of in vivo/in vitro Bond Degradation in Self-etch Adhesives
Authors: Donmez N. , Belli S. , Pashley D.H. , Tay F.R.
Published: January 2009

The morphologic correlates of bond degradation in self-etching primers have not been fully elucidated. We hypothesized that there is no difference between the mechanism of degradation of self-etching primers in vivo and in vitro. Class I cavities prepared in vivo in 24 caries-free human molars were bonded with Clearfil SE Bond or Clearfil Protect Bond, and restored with resin composites. Eight teeth were extracted after 24 hrs, and the rest after 1 yr. The same protocol was repeated in vitro with extracted molars. Degradation of resin-dentin bonds was assessed by microtensile bond testing and TEM of interfaces after tracer immersion. Both in vivo and in vitro bond strengths decreased with time for SE Bond but not for Protect Bond, with more pronounced water treeing observed in the former adhesive under both aging conditions. There is no difference between the mechanism of degradation of self-etch adhesives in vivo or in vitro.