Biomedical subjects

J Timothy Wright

Publications and source records attributed to J Timothy Wright.

16 recordsLinked to original sources

PubMed2006

The molecular etiologies and associated phenotypes of amelogenesis imperfecta.

The amelogenesis imperfectas (AIs) are a clinically and genetically diverse group of conditions that are caused by mutations in a variety of genes that are critical for normal enamel formation. To date, mutations have been identified in four genes (AMELX, ENAM, KLK4, MMP20) known to be involved in enamel formation. Additional yet to be identified genes also are implicated in the etiology of AI based on linkage studies. The diverse and often unique phenotypes resulting from the different allelic and non-allelic mutations in these genes provide an opportunity to better understand the role of these genes and their related proteins in enamel formation. Understanding the AI phenotypes also provides an aid to clinicians in directing molecular studies aimed at delineating the genetic basis underlying these diverse clinical conditions. Our current knowledge of the known mutations and associated phenotypes of the different AI subtypes are reviewed.

Amelogenesis Imperfecta↗

PubMed2006

Cloning of rat amelotin and localization of the protein to the basal lamina of maturation stage ameloblasts and junctional epithelium.

Formation of tooth enamel is a very complex process in which a specific set of proteins secreted by ameloblasts play a primordial role. As part of a screening procedure to identify novel proteins secreted by EO (enamel organ) cells of rat incisors, we isolated a partial cDNA fragment (EO-017) that is the homologue of the recently described mouse Amtn (amelotin) gene [Iwasaki, Bajenova, Somogyi-Ganss, Miller, Nguyen, Nourkeyhani, Gao, Wendel and Ganss (2005) J. Dent. Res. 84, 1127-1132]. Presented herein is the cloning of rat and pig full-length cDNAs with their deduced protein sequences. Detailed expression profiling by Northern-blot analysis and RT (reverse transcriptase)-PCR on rat and mouse tissues revealed highest expression in the mandible, more specifically in the maturation stage of the EO. Among all tissues tested, low expression was detected only in periodontal ligament, lung, thymus and gingiva. In silico analyses revealed that the Amtn gene is highly conserved in seven other mammals, but is absent from fish, birds and amphibians. The Amtn protein is enriched in proline, leucine, glutamine and threonine (52% of total) and contains a perfectly conserved protein kinase CK2 phosphorylation site. Transient transfection experiments in HEK-293 cells (human embryonic kidney cells) showed that secreted Amtn is post-translationally modified possibly through O-linked oligosaccharides on threonine residues. In concordance with its predominant expression site, immunofluorescence localization within the rat and mouse mandibles revealed Amtn localized to the basal lamina of maturation stage ameloblasts of incisors and unerupted molars. Intense Amtn protein expression was also detected in the internal basal lamina of junctional epithelium in molars. The peculiar and unique cellular localization of Amtn suggests a role in cell adhesion.

Ameloblasts↗

PubMed2006

MMP-20 is predominately a tooth-specific enzyme with a deep catalytic pocket that hydrolyzes type V collagen.

Matrix metalloproteinase-20 (MMP-20, enamelysin) has a highly restricted pattern of expression. In healthy tissues, MMP-20 is observed in the enamel organ and pulp organ of developing teeth and is present only as an activated enzyme. To identify other tissues that may express MMP-20, we performed a systematic mouse tissue expression screen. Among the non-tooth tissues assayed, MMP-20 transcripts were identified only in minute quantities within the large intestine. The murine Mmp20 promoter was cloned, sequenced, and assessed for potential tooth-specific regulatory elements. In silico analysis identified four promoter modules that were common to Mmp20 and at least two of three coregulated predominantly tooth-specific genes that encode ameloblastin, amelogenin, and enamelin. We asked if the highly restricted MMP-20 expression pattern was associated with a broad substrate specificity that might preclude its expression in other tissues. An iterative mixture-based random doedecamer peptide library screen with Edman sequencing of MMP-20 cleavage products revealed that, among MMPs previously screened, MMP-20 had unique substrate preferences. These preferences indicate that MMP-20 has a deep and wide catalytic pocket that can accommodate substrates with large aromatic residues in the P1' position. On the basis of matrices derived from the peptide library data, we identified and then confirmed that type V collagen is an MMP-20 substrate. Since type V collagen is not present in dental enamel but is an otherwise widely distributed collagen, and since only active MMP-20 has been observed in teeth, our data suggest that control of MMP-20 activity is primarily regulated by transcriptional means.

Animals↗

PubMed2006

A developmental comparison of matrix metalloproteinase-20 and amelogenin null mouse enamel.

Mutations in both the human amelogenin and human matrix metalloproteinase-20 (MMP20, enamelysin) genes cause amelogenesis imperfecta. Both genes have also been individually deleted from the mouse and each deletion results in defective dental enamel. Here, we compare the stage-specific progression of enamel development in continuously erupting mouse incisors from amelogenin null and MMP-20 null mice. Our goal was to closely examine differences in enamel and enamel organ structure between these mice that would allow a better understanding of each protein's function. The predominant feature of the amelogenin null incisors was the late onset of mineral deposition, with little or no protein present within the forming mineral. Conversely, the developing MMP-20 null incisors had a layer of protein between the apical surface of the ameloblasts and the forming enamel. Furthermore, the protein present within the enamel matrix was disorganized. An analysis of crystal structure demonstrated that the thin amelogenin null enamel was plate-like, while the MMP-20 null enamel had a disrupted prism pattern. These results suggest that amelogenin is essential for appositional crystal growth during the early to mid-secretory stage and for the maintenance of the crystal ribbon structure. They also suggest that MMP-20 is responsible for enamel matrix organization and for subsequent efficient reabsorption of enamel matrix proteins. Both genes are essential for the generation of full-thickness enamel containing the characteristic decussating prism pattern.

Absorption↗

PubMed2006

Remineralization potential of a fluoridated carbamide peroxide whitening gel.

PURPOSE: Little knowledge exists regarding the potential remineralizing benefits of adding fluoride to carbamide peroxide-based whitening gels. The aim of this project was to evaluate whether a whitening system with fluoride will remineralize previously demineralized enamel. MATERIALS AND METHODS: Twenty-four extracted teeth were sectioned into quadrants labeled A to D. Tooth quadrants in groups A, B, and D were demineralized with a lactic acid, methyl-cellulose gel system to mimic incipient carious lesions. Group C was neither demineralized nor treated. Group D was demineralized, but not treated with a whitening gel. Groups A and B were exposed to one of two commercially prepared 10% carbamide peroxide whitening gels: one that was fluoride free (group A) and one that contained fluoride (0.463%NaF) (group B). Remineralization was evaluated histologically and analyzed statistically using paired t tests accepting p < 0.05 as significant. RESULTS: Shade comparisons showed equal whitening efficacy of both gel A and B. Paired t tests show a significant reduction in lesion depth after treatment with the fluoride containing gel (B: mean lesion depth = 100 microm; p < 0.01), while there was no difference for the gel lacking fluoride (A: mean lesion depth = 110 microm). CONCLUSION: Under the conditions of this study, the addition of fluoride to a tooth whitening system does not affect the gel's whitening efficacy. The addition of fluoride could provide remineralization properties to the gel. As tooth whitening therapies continue to grow and evolve, a strong focus should rest on improving these materials in ways that will provide ever greater patient benefits. Coupling the esthetic benefits of whitening with the preventive benefits of fluoride is a natural step in this direction. CLINICAL SIGNIFICANCE: Therapuetic quantities of fluoride can impact remineralization properties of commercially available tooth whitening gels without altering whitening properties.

Carbamide Peroxide↗

PubMed2006

Diagnosis and treatment of molar incisor hypomineralization.

Molar incisor hypomineralization (MIH) is a relatively common condition that varies in clinical severity and can result in early loss of the permanent 6-year molars. The etiology of MIH remains unclear, and the diagnosis can be confused with more generalized enamel defects such as those that occur in amelogenesis imperfecta. The management of MIH depends largely on the severity of the enamel defect. Degrees of hypomineralization can range from mild enamel opacities to enamel that readily abrades from the tooth as it emerges into the oral cavity. Usually, severely affected molars are extremely hypersensitive, prone to rapid caries development, and can be difficult to manage in young patients. The purpose of this article is to review approaches to diagnosing and treating MIH.

Dental Enamel↗

PubMed2005

The use of animal models to explore amelogenin variants in amelogenesis imperfecta.

Amelogenin proteins are secreted by ameloblast cells during tooth development. Because of extensive alternative splicing of the amelogenin primary RNA transcript, and because systematic proteolysis results in many additional peptides during enamel maturation, it has been difficult to assign function to individual amelogenins. Targeted deletions and transgenic mice have been generated in order to better understand amelogenin protein function in vivo. From these murine models, we have determined that amelogenins are responsible for normal enamel thickness and structure, but not for initiation of enamel mineral formation at the dentin-enamel junction. Although it is now clear that the amelogenin (AmelX) gene exists in a nested orientation and that AmelX is expressed at a low level in various developing tissues, the significance of these findings is incompletely understood. Future studies are expected to answer remaining questions concerning structure/function relationships among these 'enamel proteins'.

Amelogenesis Imperfecta↗

PubMed2005

The psychosocial impact of developmental dental defects in people with hereditary amelogenesis imperfecta.

BACKGROUND: Amelogenesis imperfecta (AI) is a hereditary dental condition with poor esthetics and dental sensitivity that frequently requires extensive dental treatment. The authors hypothesized that AI is associated with a negative psychosocial outcome. METHODS: Family members with and without AI completed a questionnaire including demographic and dental history questions, as well as a number of psychometric scales. The authors investigated the effects of AI status (with versus without), sex and age on each of the psychosocial outcomes using a generalized linear model. RESULTS: Subjects with AI (n = 30) had higher levels of social avoidance and distress, as well as higher levels of dysfunction, discomfort and disability attributable to their oral condition compared with subjects without AI (n = 29). The relationship of AI status to fear of negative evaluation, mastery and self-esteem was age-dependent. Younger subjects with AI tended to have higher fear of negative evaluation scores, while older subjects without AI tended to have higher fear of negative evaluation scores. Additionally, subjects without AI showed a definite decrease in mastery and self-esteem scores with age, while subjects with AI tended to show an increase in mastery and self-esteem scores with age. CONCLUSIONS: These results indicate that having AI has a marked impact on the psychosocial health of affected people comparable with the impact of systemic health conditions, especially at younger ages. CLINICAL IMPLICATIONS: Dental coverage for AI traditionally is excluded by third-party payers as being solely for esthetic reasons. The authors' study shows that AI has marked psychosocial effects, which suggests that dental treatment could be medically necessary and has far-reaching implications for the affected person's overall health.

Adult↗

PubMed2005

A costs analysis of dental treatment for ectodermal dysplasia.

OVERVIEW: Dental treatment modalities for ectodermal dysplasia (ED) vary markedly depending on the clinical manifestations, but to date there have been no studies exploring the potential economic impact of ED. On the basis of anecdotal and clinical reports, the authors postulate that costs of dental treatment for this condition can have a substantial financial impact on patients and their families. OBJECTIVE: The purpose of the authors' pilot study was to develop an economic model for various treatment modalities for ED with severe hypodontia. METHODS: The authors first used a comprehensive review of the literature and expert consensus to establish a treatment modalities model for ED. Next, they completed chart reviews to validate the model with sample treatment and costs information. Using these data, they then constructed a model of treatment options and associated costs. RESULTS: The sample included 24 patients with ED who had severe hypodontia. Forty-two percent were female; patients' ages ranged from 4 years, 11 months to 31 years, 1 month. Forty-two percent had dental insurance coverage, while more than one-half paid for services out of pocket. An estimated 84 percent had undergone prosthodontic treatment, 37 percent orthodontic treatment and 19 percent implant surgery. Depending on the age of the patient and types of dental treatment, there was a broad variation in costs. This ranged from $2,038 to $3,298 for those who had received prosthodontic treatment only; it ranged from $12,632 to $41,146 for those who had received a combination of prosthodontic, orthodontic and implant treatment. CONCLUSIONS: Dental treatment for ED had a marked financial impact on patients and their families and varied depending on the type and duration of treatment.

Adolescent↗

PubMed2004

Increased bone density associated with DLX3 mutation in the tricho-dento-osseous syndrome.

Tricho-dento-osseous syndrome (TDO) (OMIM #190320) is an autosomal dominant disorder characterized and named for the three most commonly affected tissues hair, teeth, and bones. Common to all individuals with TDO studied to date is a four base-pair deletion in the DLX3 gene on chromosome 17q21. This mutation is associated with a variable bone phenotype that includes alteration in intramembranous bone formation in the skull. The purpose of this study was to characterize and compare endochondral bone phenotypes and variability at central and peripheral locations of the skeleton by evaluating bone density in individuals having the same DLX3, 4 bp DEL,NT3198 mutation (OMIM 600525) and non-affected family members using dual-energy x-ray absorptiometry (DEXA). Thirty-four individuals (20 TDO-affected and 14 non-affected) participated in this prospective study. All participants were evaluated for the DLX3 mutation associated with TDO. All subjects received DEXA scans at common, literature-supported osteoporotic test regions including: (1) non-dominant distal radius/ulna, (2) femoral neck, and (3) lumbar spine L2-4. There was a significant increase (P < 0.05) in bone mineral density in TDO-affected individuals compared with control individuals at each test region. The markedly increased bone density in individuals having the DLX3, 4 bp DEL,NT3198 mutation shows that this alteration affects both endochondral and intramembranous bone formation and suggests that the DLX3 gene is important in bone formation and/or homeostasis of the appendicular skeleton.

Abnormalities, Multiple↗

PubMed2004

Phenotypic diversity and revision of the nomenclature for autosomal recessive amelogenesis imperfecta.

PURPOSE: The purpose of this study was to characterize the phenotype in 9 families with autosomal recessive amelogenesis imperfecta (ARAI), and to propose a classification system allowing inclusion and delineation of diverse ARAI phenotypes. STUDY DESIGN: Nine families with ARAI were evaluated clinically and radiographically. Exfoliated and extracted teeth were examined via light and scanning electron microscopy, with the enamel in one case evaluated by amino acid analysis. RESULTS: The 9 families demonstrated diverse ARAI phenotypes including localized hypoplastic, generalized thin hypoplastic, hypocalcified and hypomaturation AI types. CONCLUSIONS: Some ARAI phenotypes observed in this study and reported in the literature cannot be classified using currently accepted ARAI nomenclature. Therefore, we propose a revised nomenclature permitting both classification of all ARAI clinical forms and inclusion of anticipated molecular-based nomenclature, such as now exists for some X-linked and autosomal dominant AI subtypes.

Amelogenesis Imperfecta↗

PubMed2003

Exclusion of candidate genes in two families with autosomal dominant hypocalcified amelogenesis imperfecta.

The amelogenesis imperfectas (AI) are a group of hereditary enamel defects characterized by clinical and genetic diversity. The most common AI types are inherited as autosomal traits. Three mutations of the enamelin (ENAM) gene have been found in cases of autosomal dominant hypoplastic AI. The gene(s) responsible for hypocalcified forms of AI have not been identified, although a number of autosomal genes have been proposed as candidates for AI based on their expression by ameloblasts, including ameloblastin and enamelin (chromosome 4q13.3), tuftelin (chromosome 1q21), enamelysin (chromosome 11q22.3-q23) and kallikrein 4 (chromosome 19q13.3-q13.4). To localize the gene(s) responsible for autosomal dominant hypocalcified AI, we evaluated support for/against linkage of AI to genetic markers spanning five AI candidate genes in two extended families. Our data excluded all proposed candidate gene regions as causal for autosomal dominant hypocalcified AI in these families. These linkage findings provide further evidence for genetic heterogeneity among families with autosomal dominant AI and indicate that, at least, some forms of autosomal dominant hypocalcified AI are not caused by a gene in the five most commonly reported AI candidate genes.

Amelogenesis Imperfecta↗

PubMed2002

Analysis of craniofacial development in children with hypohidrotic ectodermal dysplasia.

Ectodermal dysplasias (ED) are a heterogeneous group of inheritable disorders characterized by abnormal development of embryologic ectoderm derivatives. The purposes of this study were to: 1) create baseline cephalometric norms for male children with ED; 2) assess craniofacial growth and development in hypohidrotic ED male children with severe hypodontia, compared with non-ED children with class I dental relationships; 3) compare the craniofacial morphology of titanium dental implant-treated ED males with non-implant-treated ED males; and 4) correlate the severity of hypodontia to craniofacial dysmorphology. Cephalometric radiographs of class I individuals and implant-treated and nontreated ED groups were used to evaluate craniofacial morphology. Traditional cephalometric landmarks and measurements were used to compare groups using the generalized estimate equation analysis. Age, gender, and the number of permanent maxillary teeth present had a significant (P =.01) explanatory relationship with the craniofacial measures when comparing untreated ED children to norms. Mean craniofacial differences between ED and non-ED children still existed when the explanatory effects of these variables were controlled, indicating dysmorphology in several craniofacial structures (e.g., cranial base, mandibular length). The number of missing maxillary permanent teeth was significantly related with craniofacial dysmorphology in the ED population. Craniofacial morphology did not differ significantly between implant-treated and nontreated ED children, suggesting that treatment with intraosseous dental implants, as applied in this population, did not rescue normal craniofacial growth and development.

Adolescent↗

PubMed2002

Food sugar substitutes: a brief review for dental clinicians.

The frequent ingestion of fermentable sugars such as sucrose, fructose, glucose and maltose is conducive to the development of caries in the teeth of susceptible individuals. Natural and artificial alternatives to these sugars have been and continue to be developed as non/low-caloric sweeteners. The US Food and Drug Administration have approved four non-caloric sweeteners at present. However, there are several other non-caloric sweeteners being commonly used in other countries. A review of these sweeteners is provided with information on a promising new agent that has not yet gained FDA approval.

Humans↗

PubMedDate not supplied

The etch-bleach-seal technique for managing stained enamel defects in young permanent incisors.

Hypomineralized enamel defects frequently are manifest as a mottled-white appearance and can be associated with variable degrees of discrete yellow-brown intrinsic staining. Numerous treatment approaches have been proposed, ranging from bleaching to enamel reduction to restorative techniques. Bleaching of hypomineralized enamel lesions, using 1 to 2 applications (10 to 15 minutes each) of 5% sodium hypochlorite, has been applied clinically. Treatment using this approach has proven successful in removing yellow-brown discolorations from lesions in young permanent teeth. Young permanent incisors with yellow-brown intrinsic discolorations can often be treated by a simple and conservative bleaching protocol using sodium hypochlorite.

Acid Etching, Dental↗

PubMedDate not supplied

Clinical success and parental satisfaction with anterior preveneered primary stainless steel crowns.

PURPOSE: The purpose of this study was to evaluate the clinical success of and parental satisfaction with treatment using prefabricated resin-faced stainless steel crowns (SSCs; Kinder Krowns, Mayclin Dental Studios, Minneapolis, Minn) on anterior primary teeth. METHODS: Patients treated with Kinder Krowns within the last 3 years were recalled for dinical evaluation and completion of a parental satisfaction survey in this retrospective cross-sectional study. Clinical evaluation was performed for crown retention, facing retention, and resin veneer wear. RESULTS: Forty-six teeth were evaluated in 12 children. The average age of the crown at the time of examination was 17.5 months (range 5-38 months). All crowns were present in the mouth, and resin fracture resulting in partial or total facing loss was seen in 24% of the crowns. No resin facing fracture or visible wear was seen in 61% of the crowns. Six crowns had total facing loss from fracture (13%), while 5 (11%) had partial facing fracture. Wear (7 crowns, 15%) was limited to less than the incisal one third of the crown. The parental satisfaction with the preveneered SSCs overall was high, with satisfaction for appearance and the shape being the lowest. CONCLUSIONS: Kinder Krown prefabricated resin-faced SSCs showed a low failure rate, and the parental satisfaction with treatment was positive.

Child, Preschool↗