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Browsing by Author "Everett, Eric T."
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Item A Comparison of Radiographic, Photographic and Anthropometric Assessments of Craniofacial Asymmetry(2002) Reese, Steven A.; Hartsfield, James K., Jr.; Everett, Eric T.; Hohlt, William F.; Shanks, James; Ward, Richard E.A series of 56 orthodontic patients from the ages of 9 to 48 were involved in a prospective study on craniofacial asymmetry at Indiana University Department of Oral Facial Development. Each of the 56 individuals had fourteen bilateral anthropometric facial measurements made which were used to quantify asymmetry based on the anthropometric technique. Standard orthodontic records were taken and routine clinical exams were performed. Fourteen bilateral landmarks similar to the anthropometric landmarks were identified and measured from posterior-anterior cephalometric radiographs. Asymmetry scores for each individual were calculated using the same mathematical method as with the anthropometric data. The correlation of the two methods was calculated statistically using Pearson Product Correlation Coefficient. In addition, 26 clinicians evaluated the same patients from frontal photographs and gave each individual an overall score based on his or her apparent asymmetry. These average scores from the examiners were compared statistically to the total asymmetry scores from both the radiographic and the anthropometric data. The hypothesis was that the anthropometric data and the radiographic data would be more closely correlated with each other than either would be with the photographic data (examiner's scores). Data in this study support the hypothesis. Although some significant correlations exist between radiographic and anthropometric methods, the correlation is not high. Neither of the methods shows a correlation with the photographic data. Different measurement techniques measure different aspects of asymmetry with different errors associated with it, and clinical decisions based only on one method must be interpreted with caution.Item A Study of Craniofacial Asymmetry in Monozygotic and Dizygotic Twins Using Posteroanterior Radiographs(2002) Russell, Jennifer A.; Hartsfield, James K., Jr.; Everett, Eric T.; Roberts, W. Eugene; Shanks, James C.; Ward, Richard E.This project investigated craniofacial asymmetry in a prospective study among monozygotic (identical) versus dizygotic (fraternal) twins and sibling pairs. Posteroanterior radiographs that had previously been collected were used in this study and the zygosity of the twins had previously been determined. We hypothesized that in this study measuring craniofacial asymmetry there would be a greater concordance between monozygotic twins than between dizygotic twins for each of the variables measured. If there were some genetic component to asymmetry, we would expect to find a greater correlation between monozygotic versus dizygotic twins and sibling pairs since monozygotic twins are genetically identical and the dizygotic twins and siblings share on average fifty percent of their genes. If there are no statistically significant differences between the monozygotic and dizygotic twin correlations as shown from the heritability value, one could conclude that genetic factors are not important in the development of craniofacial asymmetry. This information is clinically significant. If we find that environment plays the predominant role in the development of asymmetry, one would conclude that clinicians should be vigilant about employing a treatment plan that will modify the environment while an asymmetry is developing. Since the zygomatico-frontal sutures and crista galli were found to be relatively symmetrical landmarks in a previous investigation by Harvold, a horizontal axis was constructed through the zygomatico-frontal sutures and a perpendicular vertical axis was constructed through crista galli. Perpendicular distances of ten bilateral structures were measured from the vertical reference line. Two methods of evaluating subjects' head positioning were used and compared. Any subject that was found to have excessive rotation of their head was excluded from the sample. After a preliminary analysis it was found that the horizontal distances were strongly correlated to patient positioning even after subjects determined to have excessive rotation of the head were eliminated from the sample. For this reason, vertical measurements of eight bilateral landmarks were made perpendicular to the reference line constructed through the zygomatico-frontal sutures. Using Statistical Package for the Social Sciences, the magnitude of craniofacial asymmetry was evaluated by calculating the absolute (non-signed) asymmetry values (IL-RI) for each of the ten horizontal and eight vertical variables. The horizontal and vertical variables were evaluated for any directional asymmetry to determine if the right or left side is consistently larger by calculating signed asymmetry values (L-R) for each of the ten horizontal and eight vertical variables. Since the subjects vary in size, relative differences were subsequently calculated. The relative difference was calculated by dividing the right-left absolute difference by half the sum of the right and left measurements [IL-Rlf.5(L+R)]. The relative difference of each of the ten horizontal and eight vertical variables was calculated for each individual. Using SAS software correlation coefficients were calculated for the relative asymmetry values of the monozygotic and dizygotic twin groups for each of the ten horizontal and eight vertical variables. Subsequently heritability values of craniofacial asymmetry were calculated for each of the eighteen variables using the standard formula h2= 2(rMz-rDz). The data revealed that head positioning had significantly affected our horizontal asymmetry values. We found a significant directionality in the horizontal and vertical dimension with the left side being larger horizontally and the right side being larger vertically. However the horizontal asymmetry values must be interpreted with caution as they are significantly affected by the rotation. After analyzing the data collected, the hypothesis was rejected. We were unable to demonstrate a significant difference in correlation values between monozygotic and dizygotic twins/sibling pairs for most craniofacial asymmetry values. The few variables that did show high heritability were in the horizontal plane. The results of the horizontal data must be interpreted with caution due to the significant effect of head rotation. In contrast it was found that vertical asymmetry values were not significantly correlated to rotation and none of these had notable estimates of heritability. These findings suggest that craniofacial asymmetry is more strongly influenced by environmental factors than genetics. This finding supports treatment by clinicians to improve or prevent developing asymmetries. While genetically controlled malformations can often be improved with treatment, environmentally induced malformations may respond well to treatment that changes the faulty developmental environment. Still it will be the capability of the patient to respond to the change in environment (treatment) that will determine the efficacy of the treatment. The interaction of genetic factors with this change in environment at a particular time as represented by the treatment may have a greater influence on the outcome of the treatment than how the problem was produced in the first place. Future studies analyzing asymmetry need to take extreme care in patient positioning and calibration of the x-ray machine, for they may lead to errors which overpower the data already subject to the error of a two-dimensional representation of a three dimensional object. Keeping these technical caveats in mind, future studies should focus on whether there are genetic factors that influence a patient's response (or the difference in response among patients) to the treatment of asymmetry.Item Assessment of Dental Asymmetry Utilizing Orthodontic Study Casts Comparing Tooth Positions to the Midpalatal Raphe and Tooth Size Among Antimeres(2002) Sprowls, Matthew W.; Hartsfield, James K., Jr.; Baldwin, James; Everett, Eric T.; Hathaway, Ronald; Shanks, James C.; Ward, Richard E.Several studies have been conducted in relation to the treatment and etiologies of craniofacial and dental asymmetries in the orthodontic scientific literature. However, limited research has attempted to correlate asymmetry in dental traits to each other. The purpose of this research study was to develop a better understanding of the correlations between dental arch asymmetry and dental tooth size asymmetry and their underlying causes. Understanding asymmetries is essential in orthodontic diagnosis and treatment planning. An orthodontist cannot obtain an optimal occlusal and functional result without properly balancing skeletal and dental relationships. Pretreatment dental study casts of 86 sequential patients from the postgraduate orthodontic clinic at the Indiana University School of Dentistry were used for the analysis. Each patient was analyzed in a single blind fashion to minimize bias. The Adobe Photoshop® ruler and Chicago® brand electronic digital calipers accurate to the nearest tenth of a millimeter were used for digital measurements. Measurements were made to determine the amount and direction of asymmetry along the dental midlines relative to the median palatine raphe. Transverse and sagittal measurements were made to record asymmetries in canine and molar positioning. Furthermore, three sets of antimeric maxillary teeth were measured for length and width. These included the central incisors, the canines, and the first molars. Fluctuating asymmetry was present in all measurements, except molar distance to median palatal raphe. This was found to be directional to the left in the entire sample group. Statistical analysis was subsequently performed and the results showed significant correlations in the individuals in the subsample dentition group. Subjects belonging to this group with a measurable degree of fluctuating asymmetry had a greater tendency toward transverse maxillary discrepancies as measured from the canines and first maxillary molars relative to the median palatal raphe. Moreover, individuals in the subsample group with above average total weighted fluctuating asymmetry values according to the parameters analyzed in this study appeared more likely to have decreased developmental stability leading to the clinical expression of more severe malocclusions.Item Differences in Craniofacial Shape among A/J and C57BL/6J Mice and their F1 Crosses(2003) Roth, Lawrence E.; Hartsfield, James K., Jr.; Everett, Eric T.; Hohlt, William F.; Shanks, James J.; Ward, Richard E.Several studies have found relationships between various craniofacial measurements and the occurrence of cleft lip (CL) in humans as well as mice. Several modes of inheritance have been proposed, some of which involve a maternal effect. In this experiment, dried skulls of CL-susceptible A/J mice, CL-resistant C57BL/6J (C57) mice and Fl mice of the two reciprocal crosses of the same were measured and compared to ascertain whether differences existed between the two Fl strains, depending on the strain of the mother. AB6/F1J (AB6) have the Fl with A/J as the mother and B6A/F1J (B6A) have C57 as the mother. Digital photographs were measured using digitizing software. Groups of two measurements were combined to form ratios describing specific shapes. Measurements and ratios were analyzed using analysis of variance (ANOVA) and discriminant analysis (DA). Oneway ANOV A showed significant differences (p < 0.05) between the two parent strains with both the measurements as well as the ratios, with A/J being smallest and C57 largest in all measurements. Univariate ANOVA controlling for weight showed little difference from the oneway ANOVA. DA was able to correctly classify 100% of both parental strains into their correct strain category. Measurements between the two Fl strains showed fewer significant differences. The B6A strain was significantly smaller than the AB6 in 3 of the 7 measurements, and the tendency was for it to be smaller in all of the measurements. This placed the Fl strains closer to their paternal strain rather than their maternal strain. The only ratio which showed significant difference between the Fl 's was the premaxillary width to interorbital width in which the B6A exhibited a narrower premaxilla when compared with its interorbital width. This was again more like its paternal strain, though with the remaining 5 ratios, the Fl 's tended to be closer to their maternal strain. DA was able to correctly classify 89% of the Fl 's into their correct strain category, indicating significant differences in overall shape between the Fl 's. Lack of a strong maternal effect in this study may be do to the age of the mice examined and/or small sample size. Future studies may do well to use the euclidean distance matrix analysis to distinguish additional differences between the 4 strains.Item Evaluation of the IL-6 Gene in External Apical Root Resorption Associated with Orthodontic Treatment(2003) Harris, Nathan P.; Hartsfield, James K., Jr.; Everett, Eric T.; Foroud, Tatiana M.; Roberts, W. Eugene; Shanks, JamesThe objective of this project is to investigate the possibility that a functional polymorphism of the interleukin-6 (IL-6) gene is associated with external apical root resorption (EARR) during orthodontic tooth movement. If genes that are involved in EARR could be identified and easily screened, the orthodontist could adjust the patient's treatment plan accordingly. Having information about a patient's susceptibility to EARR could help diagnose and treat a patient accordingly. This would allow orthodontists to monitor patients more closely or modify the treatment plan to minimize the amount EARR. The study sample consists of 60 subjects from 36 different families. The siblings had received orthodontic treatment at Indiana University School of Dentistry or in the private practice of Dr. James V. Macri. EARR was not a prerequisite to be included in this sample. Informed consent was obtained for sample collection. This study received Indiana University School of Dentistry Student Research Subcommittee Review and Indiana University Purdue University at Indianapolis Institutional Review Board approval. No significant difference between any of the IL-6 genotypes and EARR could be noted. The hypothesis that individuals with the IL-6 -174 C/C genotype would show a greater amount of EARR during orthodontic treatment could not be supported.Item Genetic Factors in External Apical Root Resorption Associated with Orthodontic Treatment(2004-06) Al-Qawasmi, Riyad A.; Hartsfield, James K., Jr.; Everett, Eric T.; Roberts, W. Eugene; Foroud, Tatiana M.; Mah, JamesExternal apical root resorption (EARR) is a common sequela of orthodontic treatment, although it may also occur without orthodontic treatment. Despite rigorous investigation, no single factor or group of factors that directly causes root resorption has been identified. Experiment 1. A sample of 83 pairs of full siblings who had undergone orthodontic treatment was studied. Measurements were made of the longest maxillary central incisor, mandibular central incisor and mesial and distal roots of the mandibular first molars. Heritability estimates were generated by generalized liner models. Our results showed that the heritability estimate of the EARR was 64% on average. It was concluded that there was sufficient heritability for EARR to pursue genetic analysis. Experiment 2. Five polymorphic markers flanking or lying within the IL-IA , IL-JB, TNSALP, TNFA, and TNFRSFJ JA genes were used in a candidate gene approach to assess linkage and association with EARR in 38 pedigrees. Suggestive evidence for linkage between EARR and the polymorphic marker D18S64 was obtained with the analysis program MAPMAKER/SIBS (LOD score 2.51). The Q-TDT program showed highly significant (p = 0.0003) evidence of linkage disequilibrium of IL-1 B polymorphisms with EARR. Our analysis indicates that the JL -1 B polymorphism accounts for 15% of the total EARR variation. Experiment 3. Nine-week-old male mice were randomly selected as controls or for placement under anesthesia of an open coil spring ligated to the left maxillary first molar producing a force of approximately 25 g. The control (C) or treated (T) per strain were A/J (C=3,T=9), C57BL/6J (C=7,T=8), C3H/HeJ (C = 4,T=6), BALB/cJ (C=4,T=6), 129P3 /J (C=6,T=8), DBA/2J (C=8,T=9), SJL/J (C=8,T= 10), and AKR/J (C=9,T =8). Animals were sacrificed after nine days of treatment or control; maxillae were immediately removed, prepared, sectioned, mounted, stained with H&E, and observed microscopically at 1 OOX to determine root resorption. Mice were grouped into root resorption resistant (A/J, C57BL/6J and SJL/J); intermediate (C3H/HeJ and AKR/J); and susceptible (BALB/cJ, DBA/2J, and 129P3/J) strains. It was concluded that there were differential susceptibility or resistance to root resorption among inbred mouse strains, indicating that genotype is an influencing factor.Item The genetic susceptibility/resistance to fluorosis among different inbred mouse strains(2003) McHenry, Melissa A.K., 1971-; Everett, Eric T.; Dean, Jeffrey A.; Gonzalez-Cabezas, Carlos, 1966-; Jackson, Richard D.; Sanders, Brian J.; Stookey, George K.Fluoridation of community water supplies for the purpose of preventing dental caries remains one of the top 10 public health interventions of the last century. However, exposure (ingestion) of greater than optimal amounts of fluoride from a variety of sources has led to an increase in the prevalence of dental fluorosis. We propose that dental fluorosis represents a complex condition caused by environmental and genetic factors. Purpose: To assess the role of genetics in the pathogenesis of dental fluorosis using genetically separate inbred strains of mice. Methods: Twelve genealogically disparate strains of mice were treated with 0 ppm, 25 ppm, and 50 ppm of fluoride in their drinking water. Each mouse was given weekly dental fluorosis evaluations. After 60 days of treatment, femurs were collected for fluoride analysis. Mandibular incisors were isolated for quantitative light induced fluorescence (QLF) studies and fluoride analysis. Digital and 35 mm images were taken of all mouse incisors in order to apply and compare the Dean's Index and the modified Thylstrup and Fejerskov Index (TFI), both indices of dental fluorosis. Skeletal radiographs were taken on the euthanized mice and later examined for extra skeletal calcifications and other gross bony deformities. Results: Differences in dental fluorosis susceptibility/resistance were identified between the strains, ranging from mild, moderate, to severe dental fluorosis. Furthermore, we found clustering of strains into distinct phenotypic groups. The A/J mouse strain was highly susceptible, with a rapid onset and severe development of dental fluorosis compared with the other strains tested. The 129P3/J mouse strain was least affected with negligible dental fluorosis. From the skeletal radiographs, no gross skeletal lesions or evidence of bone dysplasia were noted. Similar body burden of fluoride, as judged from analysis of mineralized tissues, was seen in all strains despite differences in their predispositions to develop dental fluorosis. Both the Dean's and TF indices are useful for classifying the stage or severity of fluorosis in mice, and there are advantages to the use of digital images over conventional 35 mm slide images. Both indices correlate well with the amount of fluoride exposure during amelogenesis; however, these indices are not promising indicators of fluoride burden during amelogenesis. Conclusions: QLF proved to be an innovative and useful tool for the quantification of dental fluorosis. Furthermore, these observations support the role of a genetic component in the pathogenesis of fluorosis.Item Genetics of Root Resorption Associated with Orthodontic Force in Mice(2006-07) Abass, Shaza K.; Hartsfield, James K., Jr.; Roberts, W. Eugene; Hock, Janet M.; Foroud, Tatiana M.; Everett, Eric T.External apical root resorption (EARR) is a common complication of orthodontic treatment. Genetic factors account for approximately 50% of the variation in EARR. Data have indicated variation in histological root resorption associated with orthodontic force (RRAOF) among different inbred strains of mice. Differences in expression of RANKL and OPG were investigated in two strains of mice with different susceptibility to RRAOF using irnmunohistochemistry. Increased localization of RANKL was detected in the tissues surrounding the root of the susceptible strain compared to the resistant strain and the controls. In contrast, increased localization of OPG was found in the tissues surrounding the roots in the resistant A/J strain compared to the susceptible DBA/2J strain. We conclude that differences in the expression of these key bone resorption mediators play a role in determining RRAOF susceptibility. Changes in serum TRAP 5b level in response to orthodontic force were investigated among female A/J, DBA/2J and BALB/cJ mice. The three strains differed in their TRAP positive cell numbers as well as their serum TRAP 5b level at baseline and when treated. A significant increase in the serum TRAP 5b level with treatment was only detected in the RRAOF susceptible DBA/2J strain, and not in RRAOF resistant strains. Our analysis indicates that differences in osteoclast/odontoclast activity play a role in susceptibility to RRAOF that is genetically determined. Serum TRAP 5b levels have a potential role in screening for individuals with greater susceptibility to root resorption. RRAOF was determined for male and female mice of the A/J, DBA/2J and BALB/cJ strains, as well as A/J x DBA/2J and A/J x BALB/cJ crosses. Sex differences were observed among the BALB/cJ strain only, with females more resistant to RRAOF when compared to males. Fis from the A/J x BALB/cJ cross were resistant suggesting that the A/J have dominant resistance alleles, while Fis from the A/J x DBA/2J cross had RRAOF intermediate between their parental A/J and DBA/2J mice, suggesting a polygenic trait. We concluded that the mode of inheritance of RRAOF in mice was polygenic in nature.Item Normal mandibular morphology of inbred mouse strains(2004) Edwards, Michelle Halum; Everett, Eric T.; Hartsfield, James K., Jr.; Jamison, Paul L.; Ward, Richard E.; Dean, Jeffrey A.Even though the molecular events and pathways that underlie craniofacial development and morphogenesis are not fully understood, it is accepted that their orchestration is influenced by the interaction of genetic and environmental factors. Inbred mouse strains represent genetically homogenous groups of individuals. It is established that mice in one strain often differ quite remarkably from mice in other inbred strains. Those phenotypic differences make mice exceptional tools for the dissection of genetic factors that influence normal and abnormal craniofacial morphogenesis. While numerous investigations have focused on abnormal morphogenesis, a comprehensive study of normal craniometric morphology across multiple inbred strains of mice has not been previously performed. The Mouse Phenome Project, an international collaboration of investigators, was formed to systematically phenotype a collection of normal inbred mouse strains. The objectives of our studies were to determine and measure differences in quantitative mandibular traits/variables within and between different inbred mouse strains, and to assess sexual di1norphism through bilateral measuren1ents of the hemimandibles. These studies were a component of the Mouse Phenome Project to collect normal craniometric data from 12 genetically heterogeneous inbred strains utilizing digital images from equal numbers of female and male mice at 7 to 8 weeks of age. Our central hypothesis was that morphometric analysis of mandibular structures from genetically disparate inbred mouse strains would reveal quantifiable differences. The null hypothesis of no difference among the strains for 1nandibular measurements was rejected. Overall, CAST/Ei and MOLF/Ei were consistently small in size measured by body weight with small skeletal structures. There was no strong pattern of body weight and site of skeletal size in the mid and heavy weighted strains. Evidence of sexual dimorphism was supported. Overall, it appears males and females that have the least significance between them are in the DBA/2J strain, followed by A/J. The strain with the most significant difference between males and females is in the C3H/HeJ strain.Item Normal Mandibular Morphology of Inbred Mouse Strains(2004) Edwards, Michelle Halum; Everett, Eric T.; Dean, Jeffrey A.; Hartsfield, James K.; Jamison, Paul L.; Ward, Richard E.Even though the molecular events and pathways that underlie craniofacial development and morphogenesis are not fully understood, it is accepted that their orchestration is influenced by the interaction of genetic and environmental factors. Inbred mouse strains represent genetically homogenous groups of individuals. It is established that mice in one strain often differ quite remarkably from mice in other inbred strains. Those phenotypic differences make mice exceptional tools for the dissection of genetic factors that influence normal and abnormal craniofacial morphogenesis. While numerous investigations have focused on abnormal morphogenesis, a comprehensive study of normal craniometric morphology across multiple inbred strains of mice has not been previously performed. The Mouse Phenome Project, an international collaboration of investigators, was formed to systematically phenotype a collection of normal inbred mouse strains. The objectives of our studies were to determine and measure differences in quantitative mandibular traits/variables within and between different inbred mouse strains, and to assess sexual dimorphism through bilateral measurements of the hemimandibles. These studies were a component of the Mouse Phenome Project to collect normal craniometric data from 12 genetically heterogeneous inbred strains utilizing digital images from equal numbers of female and male mice at 7 to 8 weeks of age. Our central hypothesis was that morphometric analysis of mandibular structures from genetically disparate inbred mouse strains would reveal quantifiable differences. The null hypothesis of no difference among the strains for mandibular measurements was rejected. Overall, CAST/Ei and MOLF/Ei were consistently small in size measured by body weight with small skeletal structures. There was no strong pattern of body weight and site of skeletal size in the mid and heavy weighted strains. Evidence of sexual dimorphism was supported. Overall, it appears males and females that have the least significance between them are in the DBA/2J strain, followed by A/J. The strain with the most significant difference between males and females is in the C3H/HeJ strain.