The purpose of this study was to substantiate previous claims that differential growth across the frontonasal suture occurs and if this differential growth pattern is caused by an increased mitotic rate of the nasal bone. Two six week old New Zealand White Rabbits were given calcein 20mg/kg IA, demeclocycline 20mg/kg IA, and BrdU 40mg/kg IA on Days 1, 11, and 14, respectively. The animals were euthanized using Ketamine 31.6mg/kg IM and Pentobarbital 100mg/kg IV. The frontonasal suture was removed from the rabbit and divided into hemisections. The right hemisection was histologically processed using standard calcified methods which were modified and used for smaller bone sections at the Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin. The left hemisection was reserved for BrdU staining at the Central Microscopy Research Facility, University of Iowa. The resultant slides were imaged and photographed using an Olympus BX-40 microscope and measured using ImageJ software (NIH). Means and standard deviations were calculated for interlabel distance and mineral apposition rate (MAR). All frontonasal suture sites demonstrated double fluorochrome labeling. Samples F2-2 and M2-1 demonstrated the predicted differential growth pattern. Samples F2-1 and M2-2 did not. No suture sites demonstrated positive staining for BrdU. Although the sample size was small (n=2), this may demononstrate a trend toward differential growth of the suture. Due to the small sample size, the labeling protocol used in this study provided limited quantitative data. Although two sections did not demonstrate more bone deposition or faster mineral apposition rate of the nasal bone, it is important to consider that these sections were of poorer quality when compared to the other sections. Higher quality sections with clear, measurable margins showed a difference between frontal and nasal bone growth in both morphology and mineral apposition rate.

Examples of asymmetric organs are found throughout the animal kingdom. Whether it is superficial like the fiddler crab’s claw or within an organism like our visceral organs, asymmetries have repeatedly evolved in nature. However, the genetic and developmental origins for asymmetric organ development remain unclear, especially for superficially paired structures. Within zebrafish, a striking example of asymmetry occurs within the ace/fgf8 mutant. The pharyngeal cartilages of these mutants develop asymmetrically 35% of the time, with more cartilages developing on the left or right side of the head, but the origins of this asymmetry are unknown. A significant proportion of mutants also exhibit situs inversus, whereby the visceral organs develop on the opposite side of the body. Here we seek to understand the temporal window most sensitive to giving rise to this asymmetry, and to understand if there is a correlation between the developing heart field and pharyngeal cartilage with respect to the direction of the asymmetry. Wild type (WT) zebrafish were exposed to SU5402 during different periods of development, and heart position as well as cartilage development was observed within the developing larvae. The direction of asymmetry (i.e., left or right biased) was also recorded in ace/fgf8 mutant heart position and cartilage number to observe if there was a correlation between the two developing fields. SU5402 experiments revealed that the time window most sensitive to the development of cartilage asymmetries was during heart looping and pharyngeal arch segmentation. Furthermore, ace/fgf8 mutants exhibited a robust correlation between ventricle position and the side of cartilage asymmetry, with more cartilages forming on the side where the ventricle is located. Given the close proximity of the heart and pharyngeal cartilage fields we suggest that the heart field is influencing the developing cartilage, with signaling permeating from the developing heart to the pharyngeal mesoderm to provide a buffer on the side of the developing ventricle.

OBJECTIVES: Cephalometric analysis is a tool used in orthodontics for craniofacial growth assessment. Magnitude and direction of mandibular growth pose challenges that may impede successful orthodontic treatment. Accurate growth prediction enables the practitioner to improve diagnostics and orthodontic treatment planning. Deep learning provides a novel method due to its ability to analyze massive quantities of data. We compared the growth prediction capabilities of a novel deep learning algorithm with an industry-standard method. METHODS: Using OrthoDx™, 17 mandibular landmarks were plotted on selected serial cephalograms of 101 growing subjects, obtained from the Forsyth Moorrees Twin Study. The Deep Learning Algorithm (DLA) was trained for a 2-year prediction with 81 subjects. X/Y coordinates of initial and final landmark positions were inputted into a multilayer perceptron that was trained to improve its growth prediction accuracy over several iterations. These parameters were then used on 20 test subjects and compared to the ground truth landmark locations to compute the accuracy. The 20 subjects’ growth was also predicted using Ricketts’s growth prediction (RGP) in Dolphin Imaging™ 11.9 and compared to the ground truth. Mean Absolute Error (MAE) of Ricketts and DLA were then compared to each other, and human landmark detection error used as a clinical reference mean (CRM). RESULTS: The 2-year mandibular growth prediction MAE was 4.21mm for DLA and 3.28mm for RGP. DLA’s error for skeletal landmarks was 2.11x larger than CRM, while RGP was 1.78x larger. For dental landmarks, DLA was 2.79x, and Ricketts was 1.73x larger than CRM. CONCLUSIONS: DLA is currently not on par with RGP for a 2-year growth prediction. However, an increase in data volume and increased training may improve DLA’s prediction accuracy. Regardless, significant future improvements to all growth prediction methods would more accurately assess growth from lateral cephalograms and improve orthodontic diagnoses and treatment plans.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21650号 / 医博第4456号 / 新制||医||1034(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 斎藤 通紀, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第19265号 / 理博第4120号 / 新制||理||1593(附属図書館) / 32267 / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 濱田 穣, 准教授 平﨑 鋭矢, 教授 中村 克樹 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

Indiana University-Purdue University Indianapolis (IUPUI) / Objective: To determine whether specific mutations within the fibroblast growth factor receptor 2 (FGFR2) gene associated with Crouzon syndrome cause a phenotype with extreme variability of expression suggesting non-penetrance in clinically normal appearing individuals. Methods: Most mutations responsible for Crouzon syndrome occur in exons IIIa(U) or IIIc(B) of the FGFR2 gene, facilitating allelotyping by using polymerase chain reaction to mediate mutation analysis. Once a specific mutation is identified in the index case, remaining affected family members and clinically normal first-degree relatives are screened in order to correlate genotype with phenotype. Results: A novel missense mutation, a G to T transversion, involving the first base of codon 362 (Ala362Ser), was identified following DNA sequencing of exon IIIc, and a specific restriction fragment length polymorphism following BstNI enzyme digestion was found in all Crouzon-affected family members and in one clinically normal-appearing parent. Pattern profile analysis demonstrated a consistent collection of abnormal cephalometric measurements in the Crouzon affected family members, and to a lesser degree, in the clinically normal parent. Conclusion: We have identified a novel missense mutation in the FGFR2 gene predicting an Ala362Ser substitution that is shared by all family members affected by Crouzon syndrome, and a clinically normal appearing father. These data support non-penetrance of Crouzon syndrome.

No description available.

No description available.