bluuebunny/crossref_metadata_2025 huggingface dataset:
Cleft Palate Cells Can Regenerate a Palatal Mucosa in vitro
Authors: Liu J. , Lamme E.N. , Steegers-Theunissen R.P.M. , Krapels I.P.C. , Bian Z. , Marres H. , Spauwen P.H.M. , Kuijpers-Jagtman A.M. , Von den Hoff J.W.
Published: January 2009

Cleft palate repair leaves full-thickness mucosal defects on the palate. Healing might be improved by implantation of a mucosal substitute. However, the genetic and phenotypic deviations of cleft palate cells may hamper tissue engineering. The aim of this study was to construct mucosal substitutes from cleft palate cells, and to compare these with substitutes from normal palatal cells, and with native palatal mucosa. Biopsies from the palatal mucosa of eight children with cleft palate and eight age-matched control individuals were taken. Three biopsies of both groups were processed for (immuno)histochemistry; 5 were used to culture mucosal substitutes. Histology showed that the substitutes from cleft-palate and non-cleft-palate cells were comparable, but the number of cell layers was less than in native palatal mucosa. All epithelial layers in native palatal mucosa and mucosal substitutes expressed the cytokeratins 5, 10, and 16, and the proliferation marker Ki67. Heparan sulphate and decorin were present in the basal membrane and the underlying connective tissue, respectively. We conclude that mucosal cells from children with cleft palate can regenerate an oral mucosa in vitro.
Heat Treatment Strengthens Human Dentin
Authors: Hayashi M. , Koychev E.V. , Okamura K. , Sugeta A. , Hongo C. , Okuyama K. , Ebisu S.
Published: January 2009

The flexural strength of Type I collagen, the major organic component of human dentin, increases with heat. We hypothesized that human dentin can be strengthened by heating, which may help prevent fracture of non-vital teeth after restoration. Beam-shaped dentin specimens were obtained from the crowns of human third molars. The dentinal tubular orientations were arranged to run parallel or perpendicular to loading surfaces. The flexural and microtensile strengths of dentin in the parallel specimens were 2- to 2.4-fold greater after being heated between 110°C and 140°C for 1 hr. The stress intensity factors at fracture also increased after specimens were heated. The x-ray diffraction analyses suggested that shrinking of the lateral packing of the collagen triple-helices from 14 Å to 11 Å was the probable cause of the strengthening of heated dentin. We conclude that heat treatment strengthens human dentin.
Clarithromycin Transport by Gingival Fibroblasts and Epithelial Cells
Authors: Chou C.-H. , Walters J.D.
Published: January 2009

Macrolide antibiotics penetrate cells, but the mechanism by which this occurs is unclear. The objective of this study was to characterize the mechanisms of clarithromycin uptake by gingival fibroblasts and oral epithelium. Cultured human gingival fibroblasts and SCC-25 cells were incubated with [3H]-clarithromycin. We assayed clarithromycin transport by measuring cell-associated radioactivity over time. Fibroblasts and epithelial cells rapidly accumulated clarithromycin, attaining steady-state intracellular concentrations within 15 minutes. Incubation in medium containing 2 μg/mL clarithromycin yielded steady-state intracellular concentrations of 75.8 μg/mL in fibroblasts and 6.6 μg/mL in SCC-25 cells. Clarithromycin transport exhibited Michaelis-Menten kinetics and was inhibited below 37°C. The Michaelis constants for fibro-blasts and SCC-25 cells were 78.4 and 227 μg/mL, respectively, while the maximum transport velocities were 264 and 381 ng/min/106 cells, respectively. Thus, both types of cells take up clarithromycin via a concentrative active transport system. By increasing intracellular clarithromycin levels, this system may enhance the effectiveness of clarithromycin against invasive periodontal pathogens.
A Longitudinal Study of Tooth Erosion in Adolescents
Authors: El Aidi H. , Bronkhorst E.M. , Truin G.J.
Published: January 2009

Incidence studies on tooth erosion among adolescents are scarce. This longitudinal study aimed at estimating the prevalence, incidence, progression, and distribution of erosion in young adolescents over a 1.5-year period. Erosion at baseline was present in 32.2% of the 622 children (mean age, 11.9 ± 0.9 yrs) and increased to 42.8% over 1.5 yrs. The prevalence of deep enamel or dentin erosion increased from 1.8% to 13.3%. It was hypothesized that more boys will suffer from erosion than girls. At baseline, no difference was found (p = 0.139), whereas 1.5 yrs later, more boys showed erosion than girls (p = 0.026). Of the erosion-free children, 24.2% developed erosion. Progression of erosion in terms of lesion depth and/or in number of lesions was 61.0% and was found more frequently in boys than in girls (p = 0.034). The distribution of erosion showed a predominance of occlusal surfaces of molars, especially the mesiobuccal cusp top, and palatal surfaces of upper anterior teeth.
Perceived Chewing Ability and Intake of Fruit and Vegetables
Authors: Bradbury J. , Thomason J.M. , Jepson N.J.A. , Walls A.W.G. , Mulvaney C.E. , Allen P.F. , Moynihan P.J.
Published: January 2009

Edentulous individuals have reduced chewing ability and lower fruit and vegetable consumption compared with dentate individuals. It has been suggested that the two are causally related. However, psychosocial factors such as attitude, self-identity, and knowledge of recommendations are predictive of intake in non-edentulous persons. The aims of this study were to: determine if perceived chewing ability was predictive of fruit and vegetable intake; explore the predictive ability of knowledge, attitude, and self-identity; and compare intake between edentulous and dentate individuals. Full denture-wearing (N = 79) and dentate persons (N = 52) completed a three-day food diary. Perceived chewing ability, sociodemographic, and psychosocial factors were assessed via self-administered questionnaire. The dentate persons consumed significantly more fruit and vegetables, but differences were not significant when juices were excluded. Perceived chewing ability explained ~ 4% variance in intake. Attitude, self-identity, and knowledge explained a further ~ 20%. If the diet of denture-wearers is to be improved, psychosocial factors, as well as perceived chewing ability, must be addressed.
Induced Premaxillary Suture Fusion: Class III Malocclusion Model
Authors: Ruan W.H. , Winger J.N. , Yu J.C. , Borke J.L.
Published: January 2009

The etiology of class III malocclusion remains unknown. The present study investigates the relationship between craniofacial morphology and premaxillary suture fusion to test the hypothesis that class III malocclusion may be related to premaxillary suture fusion. Cyanoacrylate was applied to immobilize the left premaxillary suture in the experimental group. Sham surgeries in rats were used for controls. Dental impressions and radiographs were taken before and after surgery for comparison of craniofacial differences between groups. Overall cranial base lengths, craniofacial widths, and craniofacial angulations related to the anterior base showed significant differences between groups. At the end of the experiment, the growth of the snout in the experimental group was inhibited and deviated to the treated side, while no obvious change was seen in the control group. The results show that induced premaxillary suture fusion can affect craniofacial morphology and indicate that premature premaxillary suture fusion may result in class III malocclusion.
Combinatorial Gene Therapy with BMP2/7 Enhances Cranial Bone Regeneration
Authors: Koh J.T. , Zhao Z. , Wang Z. , Lewis I.S. , Krebsbach P.H. , Franceschi R.T.
Published: January 2009

BMP2/7 heterodimer expression by adenovirus can stimulate bone formation at subcutaneous sites. In the present study, we evaluate whether this approach will also promote healing of cranial defects. Adenovirus expressing BMP2 or BMP7 (AdBMP2, AdBMP7) was titrated to yield equivalent BMP protein levels after transduction into murine BLK cells. Analysis of conditioned medium showed that BMP2/7 heterodimers have enhanced ability to stimulate alkaline phosphatase and Smad 1,5,8 phosphorylation relative to equivalent amounts of BMP2 or BMP7 homodimers. To measure bone regeneration, we implanted virally transduced BLK cells into critical-sized calvarial defects generated in C57BL6 mice. AdBMP2/7-transduced cells were more effective in healing cranial defects than were cells individually transduced with AdBMP2 or BMP7. Dramatic increases in bone volume fraction, as measured by microCT, as well as fusion of regenerated bone with the defect margins were noted. Thus, the use of gene therapy to express heterodimeric BMPs is a promising potential therapy for healing craniofacial bones.
Trabecular Bone Structures in the Edentulous Diastema of Osteoporotic Sheep
Authors: Dvorak G. , Gruber R. , Huber C.D. , Goldhahn J. , Zanoni G. , Salaberger D. , Watzek G. , Haas R.
Published: January 2009

The edentulous ovine diastema represents a suitable region for implantological research. Due to distinctive embryonic origin and mechanical loading, the edentulous diastema may respond differently to osteoporosis than tooth-bearing areas. To test this assumption, we subjected geriatric sheep to ovariectomy, calcium-/vitamin-D-restricted diet, and methylprednisolone administration. Adult control sheep remained untreated. Structural parameters and bone mineral density were determined by microcomputed tomography and conventional computed tomography, respectively. We report that the trabecular microstructure in the diastema was preserved from catabolic changes. In contrast, the premolar maxillary region of osteoporotic sheep had diminished trabecular bone mineral density, with the corresponding structural deteriorations. These results suggest that maxillary trabecular bone of the edentulous diastema does not respond to catabolic changes which occur in the tooth-bearing area in osteoporosis. Our findings imply that regional anatomic domains must be considered in the planning of pre-clinical studies, taking osteoporotic changes into account.
Silica Nanoparticles to Polish Tooth Surfaces for Caries Prevention
Authors: Gaikwad R.M. , Sokolov I.
Published: January 2009

Although silica particles have been used for tooth polishing, polishing with nanosized particles has not been reported. Here we hypothesize that such polishing may protect tooth surfaces against the damage caused by cariogenic bacteria, because the bacteria can be easily removed from such polished surfaces. This was tested on human teeth ex vivo. The roughness of the polished surfaces was measured with atomic force microscopy (AFM). A considerably lower nanometer-scale roughness was obtained when silica nanoparticles were used to polish the tooth surfaces, as compared with conventional polishing pastes. Bacterial attachment to the dental surfaces was studied for Streptococcus mutans, the most abundant cariogenic bacteria. We demonstrated that it is easier to remove bacteria from areas polished with silica nanoparticles. The results demonstrate the advantage of using silica nanoparticles as abrasives for tooth polishing.
Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences
Authors: Diamond G. , Beckloff N. , Ryan L.K.
Published: January 2009

Peptides with broad-spectrum antimicrobial activity are found in the mucosal surfaces at many sites in the body, including the airway, the oral cavity, and the digestive tract. Based on their in vitro antimicrobial and other immunomodulatory activities, these host defense peptides have been proposed to play an important role in the innate defense against pathogenic microbial colonization. The genes that encode these peptides are up-regulated by pathogens, further supporting their role in innate immune defense. However, the differences in the local microbial environments between the generally sterile airway and the highly colonized oral cavity suggest a more complex role for these peptides in innate immunity. For example, β-defensin genes are induced in the airway by all bacteria and Toll-like receptor (TLR) agonists primarily through an NF-κB-mediated pathway. In contrast, the same genes are induced in the gingival epithelium by only a subset of bacteria and TLR ligands, via different pathways. Furthermore, the environments into which the peptides are secreted—specifically saliva, gingival crevicular fluid, and airway surface fluid—differ greatly and can effect their respective activities in host defense. In this review, we examine the differences and similarities between host defense peptides in the oral cavity and the airway, to gain a better understanding of their contributions to immunity.
Cathepsin C Gene Variants in Aggressive Periodontitis
Authors: Noack B. , Görgens H. , Hempel U. , Fanghänel J. , Hoffmann Th. , Ziegler A. , Schackert H.K.
Published: January 2009

Cathepsin C ( CTSC) mutations are known to cause Papillon-Lefèvre syndrome. The aim of this study was to examine the association of CTSC genotype with susceptibility to non-syndromic aggressive periodontitis. The CTSC gene was analyzed in 110 persons with generalized aggressive periodontitis in comparison with 78 control individuals, after identifying different variants in a cohort of 100 persons. Five out of 19 discovered variants were included in this association study, representing 5 single-nucleotide polymorphism groups in tight linkage disequilibrium. The relevance of genotypes on enzyme function was examined. The carrier frequency of the missense variant p.I453V was significantly increased in persons with disease compared with healthy control individuals (17.3% vs. 6.4%, p < 0.05). CTSC activity in leukocytes from individuals harboring this variant was significantly reduced (119.8 ΔOD/min*105 cells, 95% confidence interval 17.4–174.9, p = 0.018). No influence of promoter variants was found on mRNA expression. The results support the hypothesis that CTSC gene variants contribute to increased susceptibility in generalized aggressive periodontitis.
Elevated Fluoride Products Enhance Remineralization of Advanced Enamel Lesions
Authors: ten Cate J.M. , Buijs M.J. , Miller C. Chaussain , Exterkate R.A.M.
Published: January 2009

Caries prevention might benefit from the use of toothpastes containing over 1500 ppm F. With few clinical studies available, the aim of this pH-cycling study was to investigate the dose response between 0 and 5000 ppm F of de- and remineralization of advanced (> 150 μm) enamel lesions. Treatments included sodium and amine fluoride, and a fluoride-free control. Mineral uptake and loss were assessed from solution calcium changes and microradiographs. Treatments with 5000 ppm F both significantly enhanced remineralization and inhibited demineralization when compared with treatments with 1500 ppm F. Slight differences in favor of amine fluoride over sodium fluoride were observed. The ratio of de- over remineralization rates decreased from 13.8 to 2.1 in the range 0 to 5000 ppm F. As much as 71 (6)% of the remineralized mineral was calculated to be resistant to dissolution during subsequent demineralization periods. With 5000-ppm-F treatments, more demineralizing episodes per day (10 vs. 2 for placebo) would still be repaired by remineralization.
Tricho-Rhino-Phalangeal Syndrome with Supernumerary Teeth
Authors: Kantaputra P. , Miletich I. , Lüdecke H.-J. , Suzuki E.Y. , Praphanphoj V. , Shivdasani R. , Wuelling M. , Vortkamp A. , Napierala D. , Sharpe P.T.
Published: January 2009

Tricho-rhino-phalangeal syndromes (TRPS) are caused by mutation or deletion of TRPS1, a gene encoding a GATA transcription factor. These disorders are characterized by abnormalities of the hair, face, and selected bones. Rare cases of individuals with TRPS displaying supernumerary teeth have been reported, but none of these has been examined molecularly. We used two different approaches to investigate a possible role of TRPS1 during tooth development. We looked at the expression of Tprs1 during mouse tooth development and analyzed the craniofacial defects of Trps1 mutant mice. In parallel, we investigated whether a 17-year-old Thai boy with clinical features of TRPS and 5 supernumerary teeth had mutation in TRPS1. We report here that Trps1 is expressed during mouse tooth development, and that an individual with TRPS with supernumerary teeth has the amino acid substitution A919V in the GATA zinc finger of TRPS1. These results suggest a role for TRPS1 in tooth morphogenesis.
Pyrosequencing analysis of the Oral Microflora of healthy adults
Authors: Keijser B.J.F. , Zaura E. , Huse S.M. , van der Vossen J.M.B.M. , Schuren F.H.J. , Montijn R.C. , ten Cate J.M. , Crielaard W.
Published: January 2009

A good definition of commensal microflora and an understanding of its relation to health are essential in preventing and combating disease. We hypothesized that the species richness of human oral microflora is underestimated. Saliva and supragingival plaque were sampled from 71 and 98 healthy adults, respectively. Amplicons from the V6 hypervariable region of the small-subunit ribosomal RNA gene were generated by PCR, pooled into saliva and plaque pools, and sequenced by means of the Genome Sequencer 20 system at 454 Life Sciences. Data were evaluated by taxonomic and rarefaction analyses. The 197,600 sequences generated yielded about 29,000 unique sequences, representing 22 taxonomic phyla. Grouping the sequences in operational taxonomic units (6%) yielded 3621 and 6888 species-level phylotypes in saliva and plaque, respectively. This work gives a radically new insight into the diversity of human oral microflora, which, with an estimated number of 19,000 phylotypes, is considerably higher than previously reported.
Fluoride Release from CaF2 and Enamel Demineralization
Authors: Tenuta L.M.A. , Cerezetti R.V. , Del Bel Cury A.A. , Tabchoury C.P.M. , Cury J.A.
Published: January 2009

The anticaries effect of professional fluoride (F) application has been attributed to calcium-fluoride-like deposits (CaF2) formed on enamel, but this has not been clearly demonstrated. We hypothesized that CaF2 formed on plaque-free enamel by F application would reduce enamel demineralization due to the increase of F availability in fluid of subsequently formed plaque. We created distinct levels of CaF2 on enamel to evaluate a dose-response effect. Enamel blocks were mounted in contact with a S. mutans test plaque and used in situ by 10 volunteers. F released to the fluid phase of this substrate (“plaque fluid”) was measured before a cariogenic challenge. “Plaque fluid” F concentration was highly correlated to the enamel CaF2 concentration (r = 0.96, p < 0.001) and to consequent enamel demineralization (r = −0.75, p < 0.001). The results suggest that F released to plaque fluid from CaF2 formed on enamel may play a significant role in the anticaries effect of professionally applied F agents.
Novel Mutations in GJA1 Cause Oculodentodigital syndrome
Authors: Fenwick A. , Richardson R.J. , Butterworth J. , Barron M.J. , Dixon M.J.
Published: January 2009

Oculodentodigital syndrome (ODD) is a rare, usually autosomal-dominant disorder that is characterized by developmental abnormalities of the face, eyes, teeth, and limbs. The most common clinical findings include a long, narrow nose, short palpebral fissures, type III syndactyly, and dental abnormalities including generalized microdontia and enamel hypoplasia. Recently, it has been shown that mutations in the gene GJA1, which encodes the gap junction protein connexin 43, underlie oculodentodigital syndrome. Gap junction communication between adjacent cells is known to be vital during embryogenesis and subsequently for normal tissue homeostasis. Here, we report 8 missense mutations in the coding region of GJA1, 6 of which have not been described previously, in ten unrelated families diagnosed with ODD. In addition, immunofluorescence analyses of a developmental series of mouse embryos and adult tissue demonstrates a strong correlation between the sites of connexin 43 expression and the clinical phenotype displayed by individuals affected by ODD.
Areca-treated Fibroblasts Enhance Tumorigenesis of Oral Epithelial Cells
Authors: Lu H.-H. , Liu C.-J. , Liu T.-Y. , Kao S.-Y. , Lin S.-C. , Chang K.-W.
Published: January 2009

Several hundred million Asians chew areca nut, which is strongly associated with oral carcinogenesis in people of this region. The impacts of areca nut extract on oral target cells are largely unclear. This study hypothesized an inductive role for areca-nut-exposed stromal cells in the progression of oral carcinomas in an at-risk population. Oral fibroblasts with chronic subtoxic areca nut extract treatment exhibited growth arrest and MMP-2 activation. The supernatant of arrested oral fibroblasts activated the AKT signaling pathway in oral carcinoma cells. The enhancement of proliferation, migration, and anchorage-independent growth of oral carcinoma cells elicited by such supernatant could be abrogated by blockers against MMP-2 or AKT. Subcutaneous co-injection of arrested oral fibroblasts into nude mice significantly enhanced the tumorigenicity of xenographic oral carcinoma cells. This study concludes that areca nut extract may impair oral fibroblasts and then modulate the progression of oral epithelial oncogenesis via their secreted molecules.
Improved Resin Infiltration of Natural Caries Lesions
Authors: Meyer-Lueckel H. , Paris S.
Published: January 2009

In artificial lesions, improved penetration and the caries-inhibiting properties of infiltrating resins could be observed with increasing penetration coefficients (PCs). The aim of the present study was to compare the penetration abilities of an experimental ‘infiltrant’ into natural lesions with those of an adhesive in vitro. Extracted human molars and premolars showing proximal white spots were cut across the lesions perpendicular to the surface. Corresponding lesion halves were etched for 120 sec with 15% hydrochloric acid gel and were subsequently treated with either an adhesive (PC: 31 cm/sec) or an infiltrant (PC: 273 cm/sec). Specimens were observed by confocal microscopy and transverse microradiography. Penetration depths of the adhesive were significantly lower compared with those of the infiltrant (p < 0.001; Wilcoxon). It can be concluded that resins with higher PCs (infiltrants) show superior ability to penetrate natural lesions compared with resins with lower PCs.
Dento-Craniofacial Phenotypes and underlying Molecular Mechanisms in Hypohidrotic Ectodermal Dysplasia (HED): a Review
Authors: Clauss F. , Manière M.-C. , Obry F. , Waltmann E. , Hadj-Rabia S. , Bodemer C. , Alembik Y. , Lesot H. , Schmittbuhl M.
Published: January 2009

The hypohidrotic ectodermal dysplasias (HED) belong to a large and heterogenous nosological group of polymalfomative syndromes characterized by dystrophy or agenesis of ectodermal derivatives. Molecular etiologies of HED consist of mutations of the genes involved in the Ectodysplasin (EDA)-NF-κB pathway. Besides the classic ectodermal signs, craniofacial and bone manifestations are associated with the phenotypic spectrum of HED. The dental phenotype of HED consists of various degrees of oligodontia with other dental abnormalities, and these are important in the early diagnosis and identification of persons with HED. Phenotypic dental markers of heterozygous females for EDA gene mutation—moderate oligodontia, conical incisors, and delayed dental eruption—are important for individuals giving reliable genetic counseling. Some dental ageneses observed in HED are also encountered in non-syndromic oligodontia. These clinical similarities may reflect possible interactions between homeobox genes implicated in early steps of odontogenesis and the Ectodysplasin (EDA)-NF-κB pathway. Craniofacial dysmorphologies and bone structural anomalies are also associated with the phenotypic spectrum of persons with HED patients. The corresponding molecular mechanisms involve altered interactions between the EDA-NF-κB pathway and signaling molecules essential in skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation. Regarding oral treatment of persons with HED, implant-supported prostheses are used with a relatively high implant survival rate. Recently, groundbreaking experimental approaches with recombinant EDA or transgenesis of EDA-A1 were developed from the perspective of systemic treatment and appear very promising. All these clinical observations and molecular data allow for the specification of the craniofacial phenotypic spectrum in HED and provide a better understanding of the mechanisms involved in the pathogenesis of this syndrome.
Regulation of CXCL9/10/11 in Oral Keratinocytes and Fibroblasts
Authors: Ohta K. , Shigeishi H. , Taki M. , Nishi H. , Higashikawa K. , Takechi M. , Kamata N.
Published: January 2009

Th1 and Th2 cytokines such as interferon-γ (IFN-γ ) , tumor necrosis factor- α (TNF-α ), and IL-4 are expressed in T-cell-mediated inflammation in the oral cavity. We tested the hypothesis that those cytokines may act on CXCR3-agonistic chemokines, T-cell recruiting factors, and on neighboring cells, including oral keratinocytes and fibroblasts. Human immortalized oral keratinocytes (RT7) and fibroblasts (GT1) after 24-hour stimulation with IFN-γ showed increased mRNA levels of CXCL9 (600- and 700-fold), CXCL10 (10,000- and 150-fold), and CXCL11 (5000- and 300-fold), respectively. In contrast, TNF-α caused an increase in CXCL9 (300-fold), CXCL10 (2000-fold), and CXCL11 (2000-fold) mRNA levels in GT1, but not RT7 cells, at 24 hrs. IL-4 reinforced the promotion of CXCL9, CXCL10, and CXCL11 expression by IFN-γ in RT7 cells, whereas IL-4 inhibited the increased levels by IFN-γ and TNF-α in GT1 cells. Thus, IFN-γ , TNF-α , and IL-4 appear cooperatively to regulate CXCR3-agonistic chemokines in oral keratinocytes and fibroblasts in T-cell-mediated oral inflammation sites.
Effect of PTK/ZK on the Angiogenic Switch in Head and Neck Tumors
Authors: Miyazawa M. , Dong Z. , Zhang Z. , Neiva K.G. , Cordeiro M.M. , Oliveira D.T. , Nör J.E.
Published: January 2009

Transformation of small avascular masses of tumor cells into rapidly progressive cancers is triggered by the angiogenic switch, a process that involves vascular endothelial growth factor (VEGF) signaling. We have shown that VEGF enhances the survival and angiogenic potential of endothelial cells by activating the Bcl-2-CXCL8 signaling axis. The purpose of this study was to evaluate the effect of a small-molecule inhibitor of VEGF receptors (PTK/ZK) on the initial stages of head and neck tumor angiogenesis. In vitro, PTK/ZK blocked head and neck tumor cell (OSCC3 or UM-SCC-17B)-induced Bcl-2 and CXCL8 expression in endothelial cells. Oral administration of PTK/ZK decreased xenograft head and neck tumor microvessel density, and inhibited Bcl-2 and CXCL8 expression in tumor-associated endothelial cells. Analysis of these data demonstrates that PTK/ZK blocks downstream targets of VEGF signaling in endothelial cells, and suggests that PTK/ZK may inhibit the angiogenic switch in head and neck tumors. Abbreviations: HDMEC, human dermal microvascular endothelial cells; VEGF, vascular endothelial growth factor; CXCL8, CXC ligand-8; PTK/ZK, PTK787/ZK222584.
Vascularization of Engineered Teeth
Authors: Nait Lechguer A. , Kuchler-Bopp S. , Hu B. , Haïkel Y. , Lesot H.
Published: January 2009

The implantation of cultured dental cell-cell re-associations allows for the reproduction of fully formed teeth, crown morphogenesis, epithelial histogenesis, mineralized dentin and enamel deposition, and root-periodontium development. Since vascularization is critical for organogenesis and tissue engineering, this work aimed to study: (a) blood vessel formation during tooth development, (b) the fate of blood vessels in cultured teeth and re-associations, and (c) vascularization after in vivo implantation. Ex vivo, blood vessels developed in the dental mesenchyme from the cap to bell stages and in the enamel organ, shortly before ameloblast differentiation. In cultured teeth and re-associations, blood-vessel-like structures remained in the peridental mesenchyme, but never developed into dental tissues. After implantation, both teeth and re-associations became revascularized, although later in the case of the re-associations. In implanted re-associations, newly formed blood vessels originated from the host, allowing for their survival, and affording conditions organ growth, mineralization, and enamel secretion.
Overlapping DSPP Mutations Cause Dentin Dysplasia and Dentinogenesis Imperfecta
Authors: McKnight D.A. , Simmer J.P. , Hart P.S. , Hart T.C. , Fisher L.W.
Published: January 2009

Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders due to mutations in DSPP. Typically, the phenotype breeds true within a family. Recently, two reports showed that 3 different net -1 bp frameshift mutations early in DSPP’s repeat domain caused DD, whereas 6 more 3′ frameshift mutations were associated with DGI. Here we identify a DD kindred with a novel -1 bp frameshift (c.3141delC) that falls within the portion of the DSPP repeat domain previously associated solely with the DGI phenotype. This new frameshift mutation shows that overlapping DSPP mutations can give rise to either DGI or DD phenotypes. Furthermore, the consistent kindred presentation of the DD or DGI phenotype appears to be dependent on an as-yet-undescribed genetic modifier closely linked to DSPP.
Statistical Issues in Assessing Powered Toothbrushes
Authors: Boardman Thomas J.
Published: January 2009

A symposium on powered toothbrushes was held at the 2000 IADR General Session. The author was asked to address statistical issues in conducting clinical studies. The objective was to cover important statistical topics that should be considered in scientific investigations, including designing the study, analyzing the results, and performing a critical scientific review. The American Dental Association (ADA) established guidelines during the 1990s. The author discusses these guidelines and addresses statistical issues they do not cover.
Defining Biomedical Informatics Competency: The Foundations of a Profession
Authors: Zimmerman J.L.
Published: January 2009

Is biomedical informatics a science or a profession? This question has been asked of many members in the biomedical informatics community, yet we still lack a response that galvanizes our community. We debate the issues over lunch. We create long, multi-threaded e-mail discussions, we write papers on the topic, and still we aren’t able to convince ourselves—let alone the rest of the scientific community. In this paper, I will describe a curriculum model for biomedical informatics and research that is developing at Columbia University, Department of Biomedical Informatics (DBMI). We believe that a strong educational foundation creates competent professionals who, in turn, comprise a bioinformatics culture. The outcome of DBMI’s curriculum design and competency project will be a set of biomedical informatics competencies which we believe will define the core knowledge and skills of the field.
Issues and Strategies for Faculty Development in Technology and Biomedical Informatics
Authors: Robinson M.A.
Published: January 2009

Biomedical informatics and technology are becoming important components of dental education. The tools and techniques now available have the potential for significant impact on teaching and research by improving the way information is acquired, stored, retrieved, and managed. However, a gap exists between those who create, introduce, or implement the technology applications and the faculty in dental schools faced with the challenge of using it. For technology and informatics to thrive in the areas of didactic teaching, clinical teaching, and clinical practice, more than a select few must understand the potential applications. This paper provides an overview of the issues and strategies involved with faculty development for the use of technology in the educational setting. The discussion covers important reasons for developing faculty competence in technology applications, significant barriers to faculty development in this area, and several strategies designed to overcome these barriers.
The Role of Information Technology and Informatics Research in the Dentist-Patient Relationship
Authors: Kirshner M.
Published: January 2009

A high-value doctor-patient relationship is based on a set of parameters which include the interpersonal relationship between the patient and the doctor. Based on the Primary Care Assessment Survey model, measures of the interpersonal relationship are associated with communication, interpersonal care, contextual knowledge of the patient, and trust. Despite the proven value of the doctor-patient relationship, current trends indicate that the quality of these relationships is on the decline. The advent of communication and information technologies has greatly affected the way in which health care is delivered and the relationship between doctors and patients. The convergence of communication and information technology with biomedical informatics offers an opportunity to affect the character of the doctor-patient relationship positively. This paper examines the intersection of the key features of the doctor-patient relationship and a variety of Internet-based, clinical, and administrative applications used in dental practice. This paper discusses the role of dental informatics research vis-à-vis the doctor-patient relationship and explores how it may inform the next generation of information technologies used in dental practice.
The Effects of HIV Infection on Oral Mucosal Immunity
Authors: Challacombe S.J. , Naglik J.R.
Published: January 2009

Oral mucosal infections, especially candidiasis, are a feature of HIV disease, suggesting that compromised mucosal immunity within the oral cavity is a consequence of the viral infection. However, how this mucosal immunity is compromised and at what stage of HIV infection this occurs are unclear. Better understanding of the protection of the oral cavity against infection has allowed us to gain some insight into the local consequences of HIV infection. From a humoral perpective, IgA2 subclasses are reduced in HIV infection in saliva, and total secretory IgA levels are reduced in later disease. Similarly, mucosal antibody responses appear near normal in early HIV infection but reduced in AIDS. There is now convincing evidence that salivary IgA can be neutralizing to HIV 1 and HIV 2, as well as block epithelial transmigration. Oral cellular immunity is also affected by HIV infection. Transmission of HIV from one oral cell type to another appears to be confirmed by work showing that HIV can bind to or infect epithelial cells, Langerhans cells, and other mucosal cells. CXCR4 tropic ( via GalCer and CXCR4) and dual tropic HIV strains have been shown to be able to infect normal human oral keratinocytes (NHOKs), and infectious HIV virions can also be conveyed from NHOKs to activated peripheral blood lymphocytes, suggesting a potential role of oral epithelial cells in the transmission of HIV infection. There is evidence of up-regulation of various receptors, including HIV receptors, on the surface of oral epithelium, and the epithelium may become more permeable. HIV may exploit this antigen uptake mechanism to cross epithelial barriers during co-infection with damage-inducing pathogens such as Candida. Immune responsiveness to many of the co-pathogens associated with HIV has been demonstrated to depend on a family of innate recognition molecules, known as Toll-like receptors (TLR), and recognition of a single pathogen can involve activation of multiple TLRs. Consequently, TLR-pathogen interactions could play an indirect but major role in regulating HIV-associated disease in the oral cavity. Thus, HIV infection appears to have both direct and indirect effects on oral mucosal immunity, affecting both cellular and humoral immunity as well as both specific and innate immunity.
Role of Human β-defensins in HIV Infection
Authors: Weinberg A. , Quiñones-Mateu M.E. , Lederman M.M.
Published: January 2009

Mechanisms of resistance to HIV-1 infection in the human oral cavity are incompletely understood. While salivary components have been implicated in protection, there is growing evidence that human beta-defensins (hBDs), originating in oral epithelial cells, may be playing an important role in the prevention of HIV infection. New antiviral, chemotactic, and immunosurveillance properties are being attributed to hBDs, which are small cationic antimicrobial innate response molecules expressed in mucosal epithelium. Inducible hBDs are always expressed in normal oral epithelium, a property not shared by other mucosal barriers. Data reviewed in this paper demonstrate that: (1) HIV-1 X4 and R5 phenotypes induce hBD-2 and -3 mRNA in normal human oral epithelial cells; (2) hBD-2 and -3 inhibit HIV-1 infection by both viral strains, with greater activity against X4 viruses; and (3) this inhibition is due to a direct interaction with virions and through modulation of the CXCR4 co-receptor. These properties may be exploited as strategies for mucosal protection against HIV-1 transmission.
Oral Mucosal Expression of HIV-1 Receptors, Co-receptors, and α-defensins: Tableau of Resistance or Susceptibility to HIV Infection?
Authors: Cutler C.W. , Jotwani R.
Published: January 2009

The basic premise of whether transmission of HIV-1 through the oral mucosa actually occurs, and through what route, is a topic of intense interest. Our work has focused on HIV-1 receptors/co-receptors and α-defensin-1 in situ in human gingiva. Regardless of HIV-1 infection, the role that C-type lectin receptors might play in periodontal pathogenesis is of great interest. We have shown that the gingival lamina propria, when inflamed, becomes increasingly infiltrated with DC-SIGN+MR+ dermal dendritic cells (DDCs), while the inflamed epithelium shows a decrease in Langerin+ Langerhans cells (LCs). Moreover, DDCs and LCs contribute to the mature CD83+ DC pool in situ, and form immune conjugates with CD4+ T-cells in the lamina propria ( Jotwani and Cutler, 2003 ). This raises the intriguing possibility that oral mucosal DCs may be involved in HIV-1 transfer to T-cells in situ. However, this possibility is tendered by the challenges faced by the virus in gaining access to oral mucosal immune cells, including their ability to survive the salivary defenses, cross the mucosal barrier, resist inactivation by α-defensins, and overcome the paucity of co-receptor CCR5 in (healthy) oral mucosa ( i.e., required for productive infection [ Jotwani et al., 2004 ]). To date, there is little evidence of direct infection by HIV-1 of oral mucosal DCs/T cells and other cells in situ. Abbreviations used in this paper: CP, chronic periodontitis; CCR5, chemokine receptor 5; CXCR4, C-X-C receptor 4; DCs, dendritic cells; DC-SIGN, DC-specific ICAM-3 grabbing non-integrin; DDC, dermal dendritic cells; LCs, Langerhans cells; LP, lamina propria; MR, mannose receptor.
Oral Lesions of HIV Disease and HAART in Industrialized Countries
Authors: Hodgson T.A. , Greenspan D. , Greenspan J.S.
Published: January 2009

The epidemiology of HIV-related oral disease in industrialized nations has evolved following the initial manifestations described in 1982. Studies from both the Americas and Europe report a decreased frequency of HIV-related oral manifestations of 10–50% following the introduction of HAART (highly active antiretroviral therapy). Evidence suggests that HAART plays an important role in controlling the occurrence of oral candidosis. The effect of HAART on reducing the incidence of oral lesions, other than oral candidosis, does not appear as significant, possibly as a result of low lesion prevalence in industrialized countries. In contrast to other oral manifestations of HIV, an increased prevalence of oral warts in patients on HAART has been reported from the USA and the UK. HIV-related salivary gland disease may show a trend of rising prevalence in the USA and Europe. The re-emergence of HIV-related oral disease may be indicative of failing therapy. A range of orofacial iatrogenic consequences of HAART has been reported, and it is often difficult to distinguish between true HIV-related oral disease manifestations and the adverse effects of HAART. A possible association between an increased risk of oral squamous cell carcinoma and HIV infection has been suggested by at least three epidemiological studies, with reference to the lip and tongue. These substantial and intensive research efforts directed toward enhancing knowledge regarding the orofacial consequences of HIV infection in the industrialized nations require dissemination in the wider health care environment.
Conceptual Emergence of Human Herpesvirus 8 (Kaposi’s Sarcoma-associated Herpesvirus) as an Oral Herpesvirus
Authors: Teo C.G.
Published: January 2009

Recognition of the various clinico-epidemiologic forms of Kaposi’s sarcoma, a disease putatively caused by an infectious agent, did not provide ready clues as to how that agent might be transmitted, although fecal and sexual routes were implicated. Application of serologic and genome-detection assays, and cell-culture studies following the identification of human herpesvirus 8 as the causative agent now implicate that virus as one that is orally shed. While oral transmission of the virus might account for the viral endemicity in Africa and Mediterranean countries, why it is particularly prevalent among male homosexuals in the West remains more difficult to explain. Such explanation may be sought from behavioral studies into the role saliva plays in sexual interactions.
(A3) HIV Phenotypes, Oral Lesions, and Management of HIV-related Disease
Authors: Blignaut E. , Patton L.L. , Nittayananta W. , Ramirez-Amador V. , Ranganathan K. , Chattopadhyay A.
Published: January 2009

Workshop participants discussed: the role of HIV subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, CD4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. Regarding HIV, the literature revealed that Type I (HIV-I), in particular group M, is involved in the majority (90%) of documented infections, and groups N and O to a lesser extent. Viral envelope diversity led to the subclassification of the virus into nine subtypes, or clades—A–D, F-H, J, and K—each dominating in different geographical areas. HIV-2, currently occurring mostly in West Africa, appears to be less virulent. No evidence could be produced of any direct impact of type, subtype, or clade on oral lesions, and participants believed that further research is not feasible. Oral candidiasis in patients from resource-poor countries should be prevented. When the condition does occur, it should be treated until all clinical symptoms disappear. Oral rinsing with an antimicrobial agent was suggested to prevent recurrence of the condition, to reduce cost, and to prevent the development of antifungal resistance. Lawsone methyl ether, isolated from a plant ( Rhinacanthus nasutus leaves) in Thailand, is a cost-effective mouthrinse with potent antifungal activity. Evidence from a carefully designed prospective longitudinal study on a Mexican cohort of HIV/AIDS patients, not receiving anti-retroviral treatment, revealed that the onset of oral candidiasis and oral hairy leukoplakia was heralded by a sustained reduction of CD4+, with an associated sharp increase in viral load. Analysis of the data obtained from a large cohort of HIV/AIDS patients in India could not establish a systemic or local cause of oral melanin pigmentation. A possible explanation was a dysfunctional immune system that increased melanin production. However, longitudinal studies may contribute to a better understanding of this phenomenon. Finally, a development plan was presented that could provide a reliable prediction of disease progression. To be useful in developing countries, the index should be independent of costly blood counts and viral load.
(B1) Candida and Mycotic Infections
Authors: Coogan M.M. , Fidel P.L. , Komesu M.C. , Maeda N. , Samaranayake L.P.
Published: January 2009

Oral candidiasis (OC) is the most common mucosal manifestation of HIV infection. This workshop examined OC and other mycoses associated with HIV infection. Historically, blood CD4 cell numbers were the primary prognosticator for the development of OC. However, a study that statistically evaluated the predictive role of HIV viral load vs. CD4 cell counts revealed viral load to be a stronger predictor for OC. The role of biofilms and antifungal resistance in recalcitrant OC is unclear at present. In general, micro-organisms including yeasts in biofilms are more resistant to antifungals than their planktonic counterparts. When the remaining organisms are eliminated, the few resistant organisms may not be problematic, because they are present in low numbers. Unusual exotic mycoses in HIV-infected patients are more common in patients from the developing than the developed world. These infections may be recurrent and recalcitrant to therapy, be present in multiple and uncommon sites, increase with the progression of HIV disease, and may play a role similar to that of the more common mycoses. Typing and subtyping of yeasts are probably not critical to the clinical management of candidiasis caused by Candida albicans and non-albicans strains, including C. dubliniensis, because it is responsive to antifungal therapy. C. glabrata is probably the only exception. The presence of oral thrush in infants younger than 6 months of age is associated with an increased post-natal transmission risk of HIV infection. Thus, perinatal retroviral therapy should be combined with the treatment of oral thrush to prevent the post-natal acquisition of HIV.
(B2) Periodontal Diseases and Other Bacterial Infections
Authors: Umadevi M. , Adeyemi O. , Patel M. , Reichart P.A. , Robinson P.G.
Published: January 2009

The workshop addressed the following questions with respect to periodontal diseases and bacterial infections seen in HIV infection: (1) What is linear gingival erythema? Is it prevalent only in HIV disease? A crude Delphi technique was used to ascertain whether LGE existed, but a consensus could not be reached. It was agreed that a diagnosis of LGE should be considered only if the lesion persists after removal of plaque in the initial visit. (2) Do periodontal pockets contribute to viremia in HIV infection? At present, the data are not available to answer this question. (3) Do anti-viral drugs reach the sulcular fluid in significant concentrations? No one at the workshop was aware of data that could answer this question. (4) Does concurrent tuberculosis infection modify the oral manifestations of HIV infection? Though analysis of data from the developing countries does suggest an association between tuberculosis and oral candidiasis, more data and multivariate analysis considering immunosuppression as a confounding factor are necessary, for any conclusions to be derived. (5) What pathogens are involved in periodontal diseases in HIV infection? Periodontal disease may be initiated by conventional periodontal pathogens. But the progression and tissue destruction depend upon the presence of typical and atypical micro-organisms, including viruses, their by-products, increased secretion of potentially destructive inflammatory mediators, and overwhelming host response. (6) How can we diagnose the diseases seen in HIV infection? The answer can be obtained only with data from controlled and blinded studies. It is necessary to design collaborative multi-center longitudinal studies. The results obtained from such large sample sizes can contribute eventually to interpretation of the outcome.