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Browsing by Author "Hartsfield, James K."
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Item A comprehensive analysis of normal variation and disease-causing mutations in the human DSPP gene(Wiley, 2008-12) McKnight, Dianalee A.; Hart, P. Suzanne; Hart, Thomas C.; Hartsfield, James K.; Wilson, Anne; Wright, J. Timothy; Fisher, Larry W.; Orthodontics and Oral Facial Genetics, School of DentistryWithin nine dentin dysplasia (DD) (type II) and dentinogenesis imperfecta (type II and III) patient/families, seven have 1 of 4 net -1 deletions within the approximately 2-kb coding repeat domain of the DSPP gene while the remaining two patients have splice-site mutations. All frameshift mutations are predicted to change the highly soluble DSPP protein into proteins with long hydrophobic amino acid repeats that could interfere with processing of normal DSPP and/or other secreted matrix proteins. We propose that all previously reported missense, nonsense, and splice-site DSPP mutations (all associated with exons 2 and 3) result in dominant phenotypes due to disruption of signal peptide-processing and/or related biochemical events that also result in interference with protein processing. This would bring the currently known dominant forms of the human disease phenotype in agreement with the normal phenotype of the heterozygous null Dspp (-/+) mice. A study of 188 normal human chromosomes revealed a hypervariable DSPP repeat domain with extraordinary rates of change including 20 slip-replication indel events and 37 predominantly C-to-T transition SNPs. The most frequent transition in the primordial 9-basepair (bp) DNA repeat was a sense-strand CpG site while a CpNpG (CAG) transition was the second most frequent SNP. Bisulfite-sequencing of genomic DNA showed that the DSPP repeat can be methylated at both motifs. This suggests that, like plants and some animals, humans methylate some CpNpG sequences. Analysis of 37 haplotypes of the highly variable DSPP gene from geographically diverse people suggests it may be a useful autosomal marker in human migration studies.Item Dental maturity of Caucasian children in the Indianapolis area(American Academy of Pediatric Dentistry, 2011-05) Weddell, Lauren S.; Hartsfield, James K.; Department of Pediatric Dentistry, School of DentistryPURPOSE: The purpose of this study was to compare chronologic and dental age using Demirjian's method. METHODS: Two hundred and fifty-seven panoramic radiographs of healthy 5- to 17.5-year-old Caucasian children in the Indianapolis area were evaluated using Demirjian's 7 tooth method. RESULTS: The intraclass correlation coefficient (ICC) for agreement with Demirjian was 0.94 (95% confidence interval [CI]: 0.87, 0.97). The ICC for repeatability of the investigator was 0.97 (95% CI=0.95, 0.99). Calculated dental age was significantly greater than chronologic age by 0.59 years (P<.001). There was no significant difference in the mean difference in ages between sexes (P=.73). Medicaid subjects had a significantly higher (P<.001) mean difference (0.82 years) than private insurance subjects (0.32 years). There was a significant negative correlation between the chronologic age and the difference in ages (r=-0.29, P<.001). Overweight (P<.001) and obese (P=.004) subjects were significantly more dentally advanced than normal (P=.35) and underweight (P=.42) subjects. CONCLUSIONS: Demirjian's method has high inter- and intraexaminer repeatability. Caucasian children in the Indianapolis area are more advanced dentally than the French-Canadian children studied by Demirjian. Difference between dental age and chronologic age varies depending on the age of the child, socioeconomic status, and body mass index.Item Effects of nicotine on osteogenesis(2001) Sanoudos, Mattheos; Roberts, W. Eugene; Christen, Arden G.; Garetto, Lawrence P.; Hartsfield, James K.; Olson, Byron L.The purpose of this study was to demonstrate the inhibiting effects of systemically administered nicotine on osteogenesis and angiogenesis. The orthopedic expansion of a suture is a non-invasive method directly related to orthodontic treatment. This study examined the actions of nicotine related to the vascularly related osteogenic response elicited by orthopedic expansion. Sixty seven male,6-8 week old, Sprague-Dawley received 2 different dosages of nicotine (6 and 12 mg/kg/day), for a period of 14 days. Nicotine was delivered subcutaneously with the use of Alzet® Osmotic minipumps. Control animals received minipumps filled with saline. Fluorochrome labels were administered during the two-week period to mark bone formation. Ten days after minipump implantation a second surgery was performed and ring-type elastic separators were placed between the maxillary central incisors of forty-six animals. Twenty-three and ninety-five hours after expansion the animals were injected BrdU and terminated 1 hour later. The maxillae were demineralized and embedded in paraffin. The femurs and tibias were cleaned from soft tissue and embedded in methyl methacrylate. The results of this study indicate that nicotine has a dose-dependent inhibiting effect on both the osteogenic and angiogenic process in the expanded suture. After 96 hours of expansion these effects are only partially reversed. Nicotine inhibits vascular invasion and depresses osteoblast recruitment. The study indicated that there may also be a direct suppression of osteoblasts, but the principal anti-osteogenic effect of nicotine is an inhibition of the vascular proliferation and osteoblast histogenesis, associated with mechanically induced osteogenesisItem Evaluation of the Treatment Effects of the Functional Regulator of Fränkel in the Correction of Angle Class II Malocclusions(2003) White, Ben G.; Roberts, W. Eugene; Baldwin, James J.; Hartsfield, James K.; Hohlt, William F.; Shanks, James C.One of the greatest challenges an orthodontist faces is the correction of Angle Class II malocclusions. Several different treatment options are available to correct saggital jaw discrepancies that often exist in these individuals. Traditionally, headgear has been used to restrain forward maxillary growth, or to distalize the maxilla. However, there is evidence that suggests that the majority of Class II skeletal relationships are due to a retrusive mandible, rather than a protrusive maxilla. Functional appliances are designed to alter the soft tissue environment of the oral facial capsule creating an environment that allows for optimal growth and development of the teeth, bones, and soft tissue. The functional regulator of Frankel (FR) is a functional appliance that is thought to act through modification of muscle and soft tissue patterns. The design of the FR has a lingual hyperpropulser subjacent to the lingual alveolar mucosa that causes a more forward posture of the mandible. It is thought by some investigators that this forward posture results in enhanced mandibular growth at the condyle which enables correction of Class II skeletal relationships. There is conflicting data regarding the efficacy of the FR at enhancing mandibular growth. Several studies show that the primary mechanisms of Class II molar correction with the FR are restrained maxillary growth, and an increase in the occlusal plane angle. Other investigations have shown enhanced mandibular growth (measured from condylion to gnathion) to be the primary mechanism of Class II correction with the FR. Due to the conflicting data that exists regarding the FR, the current study was conducted to further elucidate the treatment effects of this appliance. Fifty cases that met the inclusion criteria of the study were randomly selected from the patient files of a private practitioner experienced with the clinical management of the FR. In order to determine the treatment effects of the FR, cephalometric analysis, as well as composite and regional superimpositions were completed. The mean change from pre- to posttreatment of the experimental group was compared to the published data of untreated Class II individuals from the University of Michigan Growth Study using a two sample t-test. The radiographs were also scanned and digitized using the Dolphin™ imaging software to determine whether the manual tracing technique was similar to the digital tracing technique by using an ANOVA with fixed effects for method, time point, method by time point interaction, and a random effect for patient. The null hypotheses for this investigation were: 1) There are no statistically significant differences (p<0.05) in the cephalometric measurements between the experimental FR group and an untreated Class II control group. In particular, there are no significant differences (P<0.05) in mean mandibular length change (Condylion-Gnathion) from pre-treatment to post-treatment between the FR treated group and controls. 2) There is no statistically significant difference (p<0.05) between the cephalometric measurements obtained from manually traced and measured cephalograms, and those obtained utilizing the Dolphin™ imaging system. The results of this study showed a statistically significant difference (p<0.02) in all cephalometric parameters indicative of enhanced mandibular growth in the FR group. Additionally, the intermaxillary relationship was found to be significantly improved in the FR treated group (p<0.01) relative to controls. These findings are similar to those reported by other investigators who have found that the FR is capable of improving the sagittal jaw relationship of Class II individuals, and that a large portion of this correction is due to enhanced mandibular growth. The present study also found statistically significant differences between the experimental group and controls for several other cephalometric categories. The appliance had a statistically significant (p<0.05) restraining influence on the forward growth of the maxilla which has been previously described as the "headgear effect". The effect the FR has on the dentition was also assessed. The present investigation found that the FR causes significant (p<0.01) flaring of the lower incisors (2.0° from pre- to posttreatment), as well as a significant (p<0.0001) reduction in the axial inclination of the upper incisors (-3.2° from pre- to post-treatment). Further, it was found through regional superimpositions that the FR resulted in significant (p<0.05) posterior movement of the upper incisors (-0.4mm from pre- to post-treatment), as well as forward movement of the lower incisors (0.8mm from pre- to post-treatment). It was found that the appliance had no statistically significant (p<0.05) effect on the sagittal movement of the upper or lower molars. The FR treated group also showed statistically significant changes in vertical cephalometric measurements. The FR group had a significantly (p<0.05) increased posterior face height (2 .5mm from pre- to post-treatment), mandibular plane angle (0.4° from pre-to post-treatment), and occlusal plane angle (0.7° from pre- to post-treatment) relative to the control group. With the exception of increased posterior face height, the increases in the other vertical cephalometric measurements are thought to be deleterious side-effects of FR therapy that may impact Class II correction, and facial esthetics. The results of the comparison of the two measurement techniques showed that in general the measurements between the two methods were similar. Only one cephalometric measurement (Co-Gn) showed a significant difference (p<0.0001) between the two methods at both time points. The intraclass correlation coefficients were found to be greater than 0.80 for all cephalometric measurements made with the exception of the occlusal plane angle (OP), and upper incisor to the SN line (1/-SN). The present study further demonstrates the ability of functional appliances to increase mandibular length. The present investigation is one of the few studies that have conducted pre- to post-treatment superimpositions to determine the treatment effects of the functional regulator of Frankel. To the author's knowledge this investigation is the first to make a comparison between manually traced and measured cephalometric measurements and those made with Dolphin™ imaging. Although several measurements were found to be statistically different between the two measurement techniques, these differences are generally less than 1 mm or 1 degree. Therefore, the difference between the two measurement techniques is not likely to be clinically significant.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.