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Examining the extent to which sex differences in three-dimensional (3D) facial soft tissue configurations are similar across diverse populations could suggest the source of the indirect evolutionary benefits of facial sexual dimorphism traits. To explore this idea, we selected two geographically distinct populations. Three-dimensional model faces were derived from 272 Turkish and Japanese men and women; their facial morphologies were evaluated using landmark and surface-based analyses. We found four common facial features related to sexual dimorphism. Both Turkish and Japanese females had a shorter lower face height, a flatter forehead, greater sagittal cheek protrusion in the infraorbital region but less prominence of the cheek in the parotid-masseteric region, and an antero-posteriorly smaller nose when compared with their male counterparts. The results indicated the possible phylogenetic contribution of the masticatory organ function and morphogenesis on sexual dimorphism of the human face in addition to previously reported biological and psychological characteristics, including sexual maturity, reproductive potential, mating success, general health, immune response, age, and personality.

A 69-year-old man who had undergone chemoradiotherapy for advanced pulmonary adenocarcinoma had bilateral testicular and adrenal gland masses on a routine follow-up examination. We performed left orchiectomy, and the histopathological examination confirmed metastatic pulmonary adenocarcinoma involving the extracted testis. He was treated for disease progression with nivolumab after unsuccessful cytotoxic chemotherapy, which resulted in regression of recurrent adrenal and right testicular tumors. We reviewed the existing literature on metastatic testicular tumors and found that testicular metastasis from lung cancer is rare and poses a chemotherapeutic challenge. Based on our experience, immune checkpoint inhibitors seem to have good efficacy for treating testicular metastasis.

A 62-year-old woman with edema and color changes in her fingers underwent computed tomography (CT); slight interstitial changes were detected in the lungs with multiple tumors in the anterior and hilar region of the liver. Based on the blood test findings, she was diagnosed with interstitial pneumonia associated with systemic sclerosis. Ultrasound-guided biopsy from the hepatic hilar lymph node revealed poorly differentiated serous adenocarcinoma cells. High serum CA-125 levels suggested primary peritoneal serous carcinoma (PPSC). Owing to increased interstitial shadows on chest CT images and worsening respiratory distress, intravenous cyclophosphamide and oral prednisolone treatment was started. The skin-related symptoms, respiratory distress, and interstitial shadows improved, and the tumor size reduced. Eighteen months later, the patient has had no exacerbation of interstitial pneumonia, and the PPSC is well controlled.

Although crizotinib shows marked antitumor activity in anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancer (NSCLC) patients, all treated patients ultimately develop resistance to this drug. Isolated central nervous system failure without progression at extracranial sites is a common progression pattern in ALK rearrangement-positive NSCLC patients treated with crizotinib. Here, we report the success of crizotinib combined with whole-brain radiotherapy in an ALK rearrangement-positive NSCLC patient who developed leptomeningeal carcinomatosis and progression of multiple brain metastases. Additionally, we focused on the mechanism involved by examining the plasma and cerebrospinal fluid concentrations of crizotinib in the present case.

Objective (1) To develop models to predict the mesio-distal crown widths of the unerupted cuspids and bicuspids in the mixed-dentitions in the Singapore Malay population. (2) To evaluate the prediction accuracy of the proposed models. Materials and Methods Dental cast records were obtained from 150 Singapore Malay orthodontic patients (70 males, mean 22.9 years; 80 females, mean 21.4 years). Mesio-distal crown widths, molar basal arch-lengths and intermolar distances were measured in the permanent maxillary and mandibular dentitions on the dental casts with a digital caliper. Regression equations for estimating the sum of the crown widths of the unerupted cuspids and bicuspids were determined using a stepwise multiple regression analysis and tested for validity. Estimations within 1.5 mm in the dental arch were deemed clinically acceptable and might not affect the decision of orthodontic tooth extraction or non-extraction in a permanent dentition as it may be compensated for by interproximal enameloplasty. As such, the prediction accuracy was defined as the percentage of the estimations falling within 1.5 mm of the actual summed widths of the cuspids and bicuspids within the dental arch and was derived using the validation dataset. Results For the male subjects, the maxillary equation of Ŷ = 8.445 + 0.716 × U2 + 0.870 × U6 had a R 2 of 0.49 and the mandibular equation of Ŷ = 4.161 + 1.173 × L2 + 0.996 × L6 had a R 2 of 0.63. For the female subjects, the maxillary equation of Ŷ = 8.826 + 0.540 × U2 + 0.607 × U6 + 0.073 × UIMD had a R 2 of 0.42 and the mandibular equation of Ŷ = 9.815 + 1.005 × L1 + 1.081 × L2 had a R 2 of 0.44. Ŷ represents the estimated sum of the mesio-distal crown widths of the unerupted cuspids and bicuspids. The prediction models had accuracies of 90–100%. Conclusion The proposed models were found to be effective for clinical use for the Singapore Malay orthodontic patients in the mixed-dentition.

The establishment of normal stomatognathic function and an acceptable facial appearance is considered an important treatment goal in orthodontics. The patient, who demonstrated posterior crossbites and jaw deviation, underwent treatment with a combined orthodontic-surgical approach utilizing maxillary transverse distraction osteogenesis, Le Fort I osteotomy, and bilateral SSRO. The smoothness of the masticatory jaw-closing movement and three-dimensional facial configuration were compared pre- and post-treatment. Correction of the posterior crossbites enabled the patient to perform smoother jaw-closing movements during chewing. Additionally, asymmetry in the morphology of the chin, cheek, and lips was reduced. These favorable changes in masticatory jaw movement kinematics and three-dimensional evaluation of the face justify the application of surgical-orthodontic treatment to improve jaw function and facial appearance.

A 65-year-old woman visited our hospital due to right chest pain and dyspnea on exertion. Chest radiography revealed decreased permeability of the right lung. Computed tomography demonstrated a huge mass in the right upper lobe and right pleural effusion. Right pleural effusion cytology yielded a diagnosis of adenocarcinoma and was positive for mutation of epidermal growth factor receptor (EGFR; exon 21 L858R). Afatinib was selected for the initial treatment. Multiple tumors regressed remarkably, but then rapidly progressed 3 months later. We performed re-biopsy to detect the mechanism of resistance to afatinib. Histopathology revealed a mixture of small cell carcinoma (SCC) and adenocarcinoma harboring same EGFR mutation. To the best of our knowledge, this is the first report of transformation to SCC after treatment with afatinib.

A 73-year-old man was referred to our hospital after a 2-week history of bloody sputum and cough. Computed tomography (CT) images of the chest showed a mass grouped with mediastinal lymph nodes, and bronchoscopy showed a projecting mass in the right main bronchus. After a transbronchial biopsy, the patient was diagnosed with squamous cell carcinoma (T4N2M0 stage IIIB). The patient was treated with systemic chemotherapy, consisting of cisplatin (40 mg/m2, days 1 and 8) and docetaxel (30 mg/m2, days 1 and 8), and concurrent thoracic irradiation at a daily dose of 2 Gy. On day 35 of treatment, the patient complained of a sore throat and cough. A CT of the chest showed punctate low-attenuation foci between the esophagus and bronchus. Gastrointestinal endoscopy and bronchoscopy demonstrated a fistula in the middle intrathoracic esophagus and the left main bronchus. The patient’s symptoms gradually improved, and the fistula was closed after the suspension of chemoradiotherapy. Radiotherapy was resumed and completed on day 82. However, on day 108, he developed a fever and cough, and a tumor with fistula was revealed in the right main bronchus. He had an esophageal stent inserted, but he later died of sudden hemoptysis.

Gamma-motoneurons (γMNs) play a crucial role in regulating isometric muscle contraction. The slow jaw-closing during mastication is one of the most functional isometric contractions, which is developed by the rank-order recruitment of alpha-motoneurons (αMNs) in a manner that reflects the size distribution of αMNs. In a mouse spinal motor nucleus, there are two populations of small and large MNs; the former was identified as a population of γMNs based on the positive expression of the transcription factor estrogen-related receptor 3 (Err3) and negative expression of the neuronal DNA-binding protein NeuN, and the latter as that of αMNs based on the opposite pattern of immunoreactivity. However, the differential identification of αMNs and γMNs in the trigeminal motor nucleus (TMN) remains an assumption based on the size of cell bodies that were retrogradely stained with HRP. We here examined the size distributions of αMNs and γMNs in the dorsolateral TMN (dl-TMN) by performing immunohistochemistry using anti-Err3 and anti-NeuN antibodies. The dl-TMN was identified by immunopositivity for vesicular glutamate transporter-1. Immunostaining for choline acetyltransferase and Err3/NeuN revealed that the dl-TMN is composed of 65% αMNs and 35% γMNs. The size distribution of αMNs was bimodal, while that of γMNs was almost the same as that of the population of small αMNs, suggesting the presence of αMNs as small as γMNs. Consistent with the size concept of motor units, the presence of smaller jaw-closing αMNs was coherent with the inclusion of jaw-closing muscle fibers with smaller diameters compared to limb muscle fibers.

Objective Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure for pulmonary and mediastinal diseases. This study compared the performance of a novel 19-G needle with a 21- or 22-G needle. Patients and Methods Eleven patients at Okayama Medical Center were enrolled retrospectively between April and December 2017. Enlarged lymph nodes and a pulmonary nodule were sampled with both 19-G and 21- or 22-G needles in nine patients. Two patients underwent biopsies for suspected lymphoma with only the 19-G needle. We examined their medical records on the diagnosis, size of the lymph nodes and pulmonary nodule, and complications. Results The median longest diameter of the 13 lymph nodes (8 #7, 4 #4R, and 1 #11) and 1 pulmonary nodule (right segment 6) in the 11 patients was 31.6 mm (range, 10.4-45.0 mm). Definitive diagnoses were made using the 19-G needle in nine patients. EBUS-TBNA with a 19-G needle resulted in successful diagnoses of one case of retinal hemangioblastoma, one case of tuberculous lymphadenitis, and one case of lung adenocarcinoma, as well as the evaluation of the programmed death-ligand 1 (PD-L1) expression following initial negative findings after a 21- or 22-G biopsy. A small pulmonary nodule (lung squamous cell carcinoma) with negative findings after a 19-G biopsy was diagnosed with a 22-G biopsy. Two suspected lymphoma patients were diagnosed with a 19-G needle: one had lymphoma and the other sarcoidosis. Three patients were diagnosed with sarcoidosis using both the 19-G and 21- or 22-G needles. Conclusion EBUS-TBNA with a 19-G needle was useful for diagnosing retinal hemangioblastoma and tuberculous lymphadenitis as well as for PD-L1 testing after 21- and 22-G biopsies were unsuccessful.

Objectives: To evaluate the test-retest reliability of three types of facial expression tasks using three-dimensional (3D) facial topography. Materials and Methods: Twelve adult volunteers were enrolled in this study. They were instructed to perform three different facial expression tasks: rest posture, posed smile, and maximum effort smile. Each task was recorded using a 3D image-capturing device on two separate occasions with an interval of 1 week between sessions. The images of two sessions were superimposed based on the forehead. For each participant and for each facial expression, a wire mesh fitting was conducted. This method generated 6,017 points on the wire mesh. Intraindividual reliability between sessions for each task was statistically tested by intraclass correlation coefficients (ICCs) and the 95% confidence interval minimal detectable change (MDC95). Results: The MDC95 for the repeated measures of the rest posture, posed smile, and maximum effort smile exhibited means of 0.8, 1.5, and 1.3 mm, respectively, on the z-axis. The ICCs ranged from substantial to almost perfect agreement for repeated measures for the rest posture and maximum effort smile (0.60 < ICC ≤ 1.00). The right corner of the mouth in the posed smile showed moderate agreement (0.40 < ICC ≤ 0.60). Conclusions: The overall test-retest reliability of the maximum effort smile and rest posture showed substantial to almost perfect agreement, and this was clinically acceptable.

The muscle contraction during voluntary movement is regulated by activities of α- and γ-motoneurons (αMNs and γMNs, respectively). The tension of jaw-closing muscles can be finely tuned over a wide range. This excellent function is likely to be achieved by the specific populations of αMNs innervating jaw-closing muscles. Indeed, we have recently demonstrated that in the rat dorsolateral trigeminal motor nucleus (dl-TMN), the size distribution of αMNs was bimodal and the population of smaller αMNs showed a size distribution similar to that of γMNs, by immunohistochemically identifying αMNs and γMNs based on the expressions of estrogen-related receptor gamma (Err3) and neuronal DNA binding protein NeuN together with ChAT. This finding suggests the presence of αMNs as small as γMNs. However, differences in the electrophysiological membrane properties between αMNs and γMNs remain unknown also in the dl-TMN. Therefore, in the present study, we studied the electrophysiological membrane properties of MNs in the dl-TMN of infant rats at postnatal days 7–12 together with their morphological properties using whole-cell current-clamp recordings followed by immunohistochemical staining with an anti-NeuN and anti-ChAT antibodies. We found that the ChAT-positive and NeuN-positive αMNs were divided into two subclasses: the first one had a larger cell body and displayed a 4-aminopyridine (4-AP)-sensitive current while the second one had a smaller cell body and displayed a less prominent 4-AP-sensitive current and a low-threshold spike, suitable for their orderly recruitment. We finally found that γMNs showing ChAT-positive and NeuN-negative immunoreactivities had smaller cell bodies and displayed an afterdepolarization mediated by flufenamate-sensitive cation current. It is suggested that these electrophysiological and morphological features of MNs in the dl-TMN are well correlated with the precise control of occlusion.

A 74-year-old man with a history of occupational asbestos exposure in a shipyard was diagnosed with lymphohistiocytoid mesothelioma (LHM). Systemic chemotherapy consisted of cisplatin, and pemetrexed was administered. After six courses of chemotherapy, multiple tumours had regressed. Six months after chemotherapy, the tumours on the pleura exhibited regrowth and partly invaded the liver. Salvage chemotherapies, including irinotecan and vinorelbine, were administered and his disease was stable for several months. Then he suddenly vomited and complained of abdominal pain. Contrast CT showed small intestine intussusception. Partial resection of the small intestine was performed. We found a tumour in the resected small intestine. Review the …

Structured Abstract Objectives To objectively classify the nose–lip–chin profiles of adult women and identify any associations between the nose–lip–chin profile patterns and dentoskeletal patterns. Setting and Sample Population Lateral facial photographs and lateral cephalograms were obtained for 229 Japanese women who were being assessed for orthodontic treatment. Methods A feature vector that was effective in distinguishing differences in nose–lip–chin profiles was extracted for each photograph. To categorize the records into an optimum number of subclasses according to nose–lip–chin profile configurations, a vector quantization method was applied to the feature vectors of all samples. Dentoskeletal patterns that corresponded to the nose–lip–chin profile subclasses were compared. Results Eight profile patterns were identified, and the differences among patterns were notably maximized by the nasolabial angle, configuration and vertical length of the subnasal region, vertical thickness of the lip vermilion borders, sagittal position of the upper- and lower-lip vermilion borders and their relation to each other, labiomental angle, depth of the labiomental sulcus, degree of prominence of the chin, and degree of protrusion of the mandible. The dentoskeletal patterns showed significant differences between the classified profile patterns (p

Cell proliferation and differentiation are closely coupled. However, we previously showed that overexpression of cyclin-dependent kinase (Cdk6) blocks chondrocyte differentiation without affecting cell-cycle progression in vitro. To investigate whether Cdk6 inhibits chondrocyte differentiation in vivo, we generated chondrocyte-specific Cdk6 transgenic mice using Col2a1 promoter. Unexpectedly, differentiation and cell-cycle progression of chondrocytes in the Cdk6 transgenic mice were similar to those in wild-type mice. Then, we generated chondrocyte-specific Ccnd1 transgenic mice and Cdk6/Ccnd1 double transgenic mice to investigate the possibility that Cdk6 inhibits chondrocyte differentiation through E2f activation. Bromodeoxyuridine (BrdU)-positive chondrocytes and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive chondrocytes were increased in number, and chondrocyte maturation was inhibited only in Cdk6/Ccnd1 transgenic mice (K6(H)/D1(H) mice), which showed dwarfism. Retinoblastoma protein (pRb) was highly phosphorylated but p107 was upregulated, and the expression of E2f target genes was dysregulated as shown by upregulation of Cdc6 but downregulation of cyclin E, dihydrofolate reductase (dhfr), Cdc25a and B-Myb in chondrocytes of K6(H)/D1(H) mice. Similarly, overexpression of Cdk6/Ccnd1 in a chondrogenic cell line ATDC5 highly phosphorylated pRb, upregulated p107, induced apoptosis, upregulated Cdc6 and downregulated cyclin E, dhfr and B-Myb and p107 small interfering RNA reversed the expression of downregulated genes. Further, introduction of kinase-negative Cdk6 and cyclin D1 abolished all effects by Cdk6/cyclin D1 in ATDC5 cells, indicating the requirement of the kinase activity on these effects. p53 deletion partially restored the size of the skeleton and almost completely rescued chondrocyte apoptosis, but failed to enhance chondrocyte proliferation in K6(H)/D1(H) mice. These findings indicated that Cdk6/Ccnd1 overexpression inhibited chondrocyte maturation and enhanced G1/S cell-cycle transition by phosphorylating pRb, but the chondrocytes failed to accomplish the cell cycle, and underwent p53-dependent apoptosis probably due to the dysregulation of E2f target genes. Our findings also indicated that p53 deletion in addition to the inactivation of Rb was not sufficient to accelerate chondrocyte proliferation, suggesting the resistance of chondrocytes to sarcomagenesis.

Sox9 is an essential transcription factor for chondrogenesis by regulating the expression of chondrogenic genes. However, its regulatory mechanism is not fully understood. To address this, we attempted to identify the transcriptional partners of Sox9 by screening the cDNA library of the chondrogenic cell line ATDC5 using the collagen 2α1 (Col2α1) gene promoter fused to a luciferase reporter gene. One of the positive clones encoded the Znf219 gene. Whole mount in situ hybridization experiments indicated that Znf219 mRNA was specifically expressed in the developing limb buds where Col2α1 and Sox9 were strongly expressed. Znf219 markedly enhanced the transcriptional activity of Sox9 on the Col2a1 gene promoter. In addition, Znf219 is physically associated with Sox9 and is colocalized with Sox9 in the nucleus. We also found that overexpression of Znf219 profoundly increased Sox9-induced mRNA expression of Col2a1, aggrecan and Col11a2. Consistently, knockdown of Znf219 decreased the Sox9-induced mRNA expression of these genes. Furthermore, a dominant-negative mutant Znf219 inhibited Bmp2-induced chondrocyte differentiation. Our results suggest that Znf219 plays an important role in the regulation of chondrocyte differentiation as a transcriptional partner of Sox9.

Little is known about projections from the cerebral cortex to the trigeminal mesencephalic nucleus (Vmes) which contains the cell bodies of primary sensory afferents innervating masticatory muscle spindles and periodontal ligaments of the teeth. To address this issue, we employed retrograde (Fluorogold, FG) and anterograde (biotinylated dextranamine, BDA) tracing techniques in the rat. After injections of FG into the Vmes, a large number of neurons were retrogradely labeled in the prefrontal cortex including the medial agranular cortex, anterior cingulate cortex, prelimbic cortex, infralimbic cortex, deep peduncular cortex and insular cortex; the labeling was bilateral, but with an ipsilateral predominance to the injection site. Almost no FG-labeled neurons were found in the somatic sensorimotor cortex. After BDA injections into the prefrontal cortex, anterogradely labeled axon fibers and boutons were distributed bilaterally in a topographic pattern within the Vmes, but with an ipsilateral predominance to the injection site. The rostral Vmes received more preferential projections from the medial agranular cortex, while the deep peduncular cortex and insular cortex projected more preferentially to the caudal Vmes. Several BDA-labeled axonal boutons made close associations (possible synaptic contacts) with the cell bodies of Vmes neurons. The present results have revealed the direct projections from the prefrontal cortex to the primary sensory neurons in the Vmes and their unique features, suggesting that deep sensory inputs conveyed by the Vmes neurons from masticatory muscle spindles and periodontal ligaments are regulated with specific biological significance in terms of the descending control by the cerebral cortex.

Objective: To investigate whether individuals with malocclusion show less skillfulness, as represented by kinematic parameters that characterize masticatory jaw movement, compared with those having normal occlusion and, if so, to examine whether more skilled movements are achieved after completion of orthodontic treatment. Materials and Methods: Lower incisor point movement in space during gum chewing was recorded, and the kinematic traits of such movement were compared among four subject groups: a Control Group (36 females with good occlusion), a Malocclusion Group (24 females with dental malocclusions), an Extraction Group (31 females who had received orthodontic treatment with premolar extraction) and a Nonextraction Group (27 females who had been treated orthodontically without tooth extraction). Before treatment, all subjects in the three experimental groups exhibited dental malocclusions and skeletal class I jaw-base relationship. Results: Compared with the Malocclusion Group, the lower normalized jerk-cost, the shorter phase durations, the more symmetric property of the velocity profile, and the smaller variance of lateral jaw-closing trajectories near the tooth intercuspation position were determined in the Extraction Group and the Nonextraction Group as well as in the Control Group. Conclusions: As measured by kinematic parameters such as normalized jerk-costs, velocity profile, and variance of movement trajectories near the endpoint of movement, dental malocclusions were associated with significantly lower skillfulness of masticatory jaw motion, whereas good occlusion and orthodontically improved occlusion (either with or without premolar extraction) were both associated with more skillful motion.

Objective: To develop a mathematical model that simulates optimum site(s) for tooth extraction and to examine what kinds of dentoskeletal traits, in the model, influence optimizing decisions for extraction site(s). Materials and Methods: Conventional orthodontic records were obtained for 193 women who had received orthodontic tooth-extraction treatments judged as excellent treatment outcomes. The feature vector-elements that represented dentoskeletal traits, and weights of their contributions to achieving optimum simulation in the model, were determined. Results: The rate of coincidence between recommendations made by the optimized model and the actual judgments was found to be 86.0%. The elements that were sensitive to increasing the rate of coincidence and corresponding weights in judging the site(s) of tooth extraction were: protrusiveness of the upper and lower incisors (2.0), overjet and overbite (1.5), the membership grade for the skeletal Class II jaw relationship, molar relationship in the sagittal direction, the mandibular plane angle, and the severity of tooth crowding in the lower dentition (1.0). The remaining 10 feature vector-elements were also found to be indispensable for the model. Conclusions: A mathematical model that simulates optimum site(s) for orthodontic tooth extraction, with a high agreement rate (86.0%) between the system's recommendations and the actual judgments given by orthodontists, was developed. The dentoskeletal structural traits that affected optimizing decisions for orthodontic tooth-extraction site(s) were formulated and subdivided into five major categories, ie, the sagittal dentoskeletal and soft tissue relationship, the vertical dentoskeletal relationship, the transverse dental relationship, the intra-arch conditions, and the pathological conditions.

This article describes a two-phase orthodontic approach to treating a young adolescent girl that had Angle Class II, Division 1 malocclusion associated with an excessive incisor overjet caused by prolonged digit sucking. The Phase I treatment utilized a tongue crib and a straight-pull headgear appliance during puberty and achieved significant improvements in the facial profile. The Phase II treatment involved edgewise appliances, a transpalatal arch and a straight-pull headgear appliance without extraction of permanent teeth. Dental and skeletal corrections were made with the two-phase treatment and stable occlusion and good facial proportion were obtained.

In patients with malocclusion and tooth-size discrepancy, the management of the tooth-size discrepancy is important. The present case report describes orthodontic treatment in a patient with moderate tooth crowding, a protruded lower lip and a high overall ratio that was caused by the large upper and lower first premolar teeth. We extracted the upper second premolar teeth and the lower first premolar teeth. After completion of active treatment, tight intercuspation of the teeth was obtained and the soft tissue profile was improved. The occlusion and the facial profile remained almost stable during the retention phase.

This paper describes orthodontic treatment combined with autotransplantation of a premolar tooth in a girl aged 8 years 10 months with dental bimaxillary protrusion associated with congenitally missing bilateral lower second premolars and the upper left first and second premolars. We transplanted the right second premolar to the socket of the left second deciduous molar tooth prior to comprehensive orthodontic treatment, and the other socket spaces were closed orthodontically appliances. Good occlusion and facial esthetics were achieved, and these results have been maintained for 3 years after completion of the active treatment.

This paper concerns orthodontic treatment of a 11-year-old female having an Angle Class III malocclusion with incisor edge-to-edge occlusion, a skeletal Class III jaw base relationship and a normal mandibular plane angle. When she was 13 years old, the mandibular third molars were extracted and the remaining mandibular molars were distalized. Good occlusion and facial esthetics were achieved. These results have been maintained for 4 years following completion of active treatment.

Large intra- and/or inter-individual variability in human masticatory motor behaviors may reduce objectivity in assessing normality/abnormality for jaw movements. Analytical simulation by kinematic modeling based on a universally accepted objective criterion is a potentially useful clinical tool for credible diagnostic quantification of jaw motion. This study aimed to test whether a minimum-jerk (maximum-smoothness) model could accurately simulate the kinematics in each separate gum-chewing cycle of 10 healthy adults, and if so, to examine whether simulation errors reflected an extent of abnormality for chewing movements for 10 patients caused by temporomandibular joint disorders (TMD). The model predicted the lower incisor-point movements of the control group with reasonable accuracy. Overall, the prediction errors for the patients group were greater than the control group, demonstrating that prediction errors for jaw opening velocity were sensitive to the criteria for joint disorders. It was concluded that the present simulation emerged as being capable of scaling the not so smooth masticatory jaw movements performed in the presence of TMD.

The amount of tooth displacement under orthodontic loads has proven to be independent of force magnitudes. The underlying bio-physical process of this phenomenon remains uncertain. The aim of this study was to describe and simulate the initial response of periodontal ligament (PDL) by means of inverse kinematic modeling. The model was developed based on the experimental data for tooth translation along a straight line. The reaction of the PDL was assumed to derive from viscoelastic and complementary elements. An algorithm of putative poroelasticity allowed the number of elements that participate in the reaction to increase in proportion to the orthodontic force. The simulation outcomes showed consistency with the measured data. The orthodontic retraction between the premolar and two-molar segment was also simulated. The two-molar displacement was 85% of that of the premolar displacement. The results demonstrate that the inverse kinematic model is capable of predicting the tooth displacement that is independent of the force magnitude.

summary Humans with normal occlusion usually perform gum-chewing movements in a characteristic manner. The purpose of present study was to examine whether the variability of masticatory jaw movement in children with incisor crossbite is greater than that in children with normal occlusions, and if so, to examine whether correction of the crossbite results in a significant reduction in the variability. The variance in masticatory jaw movement trajectory was investigated in 10 children with acceptable occlusion and 11 children with crossbite of one or two incisors. The lower incisor-point movements during chewing of standardized gum were monitored using a 3D tracking device. The deviation of the jaw-closing trajectory from a best-fit plane was then evaluated for each chewing cycle. Subsequently, variance in angles of the best-fit planes and variance in the instantaneous curvature of the jaw-closing trajectories were evaluated. Pitch angles of the best-fit planes and curvature of the trajectories during closing in patients were more variable than those in control subjects (P

The differentiation of mesenchymal cells into chondrocytes and chondrocyte proliferation and maturation are fundamental steps in skeletal development. Runx2 is essential for osteoblast differentiation and is involved in chondrocyte maturation. Although chondrocyte maturation is delayed in Runx2-deficient (Runx2–/–) mice, terminal differentiation of chondrocytes does occur, indicating that additional factors are involved in chondrocyte maturation. We investigated the involvement of Runx3 in chondrocyte differentiation by generating Runx2-and-Runx3-deficient (Runx2–/–3–/–) mice. We found that chondrocyte differentiation was inhibited depending on the dosages of Runx2 and Runx3, and Runx2–/–3–/– mice showed a complete absence of chondrocyte maturation. Further, the length of the limbs was reduced depending on the dosages of Runx2 and Runx3, due to reduced and disorganized chondrocyte proliferation and reduced cell size in the diaphyses. Runx2–/–3–/– mice did not express Ihh, which regulates chondrocyte proliferation and maturation. Adenoviral introduction of Runx2 in Runx2–/– chondrocyte cultures strongly induced Ihh expression. Moreover, Runx2 directly bound to the promoter region of the Ihh gene and strongly induced expression of the reporter gene driven by the Ihh promoter. These findings demonstrate that Runx2 and Runx3 are essential for chondrocyte maturation and that Runx2 regulates limb growth by organizing chondrocyte maturation and proliferation through the induction of Ihh expression.

The effect of a long mental stress on the hemodynamics of masticatory muscles has not been investigated to date. We hypothesized some hemodynamic and electromyographic changes in jaw-closure muscles related to sympathetic nervous system activity. While healthy adult female volunteers performed a two-hour mental stress task, electromyographic activity of the temporal and masseteric muscles was recorded, and hemodynamic changes of the masseter muscle were measured non-invasively. Autonomic function was assessed by heart rate spectral analysis. Integrated electromyographic activity of the temporalis muscle, but not the masseter muscle, showed an increase that coincided with the increase in sympathetic nervous activity. In the masseter muscle, despite little change in integrated electromyographic activity, notable changes were found in hemodynamic parameters. These results suggest that hemodynamics of jaw muscles is susceptible to mental stress, implying a potential role in the etiology of jaw muscle dysfunction associated with mental stress.

A 15-year-old patient is presented with 11 impacted teeth including 2 supernumerary teeth, who did not exhibit hereditary or clinical disease. The patient showed the extruded and lingually inclined lower incisors, the anteriorly inclined palatal plane, extremely large curve of Spee, and crowding in the bone. A detailed description of the positional relationship between each impacted tooth and the neighboring tooth was given using the 3D CT-image.

MR images of the temporomandibular joint at occlusion and at various stages of mouth opening were registered and reconstructed three-dimensionally before and after a modified condylotomy in a patient with painful disk displacement. Following the condylotomy, the condyle/disk relationship had become normalized in all three planes of space at closed mouth and during mouth opening. The post-operative distances of the condylar and diskal paths had increased when compared with the preoperative distances. The three-dimensional visualizing method may, besides providing diagnostic advantages, be a valuable tool for qualitative and quantitative documentation of the efficiency of different treatment methods for normalization of the disk/condyle relationship in patients with TMJ disk displacement.

Objective To present the morphology of the extremities, craniofacial structures, and the oral cavity based on roentgencephalometry and three-dimensional computed tomography and magnetic resonance imaging scanning in a patient with hypoglossia-hypodactylia syndrome, discuss the orthodontic treatment method, and review the literature for the syndrome. Patient The patient was a 6-year-old boy diagnosed with hypoglossia-hypodactylia syndrome at birth. He had hypodactylia as well as micrognathia with steep inclination of the anterior surface of the mandible in relation to the lower mandibular plane. He had missing mandibular incisors with concomitant bone defect limited to the associated alveolar ridge and an absence of any malformations in the mandibular ramus and condylar head. The patient had a bilateral scissors bite with an extremely constricted mandibular dental arch, skeletal Class II jaw relationship with an average mandibular plane angle and maxillary incisors inclined palatally. He had extremely reduced tongue size and hypertrophy of the floor of the mouth. Anomalies of the central nervous system were not observed. There was no evidence of hearing loss.

In humans, the inappropriate occlusal vertical dimension (OVD) causes several orofacial disorders, such as bruxism and pain in the masticatory muscles and temporomandibular joint. However, it is still unclear how strictly the OVD is adjusted. To answer this question, we studied the temporal change of the OVD in bite-raised young guinea pigs. The OVD was raised by fixation of a bite-raising appliance to the lower incisors, and increased by either 3 or 1.5 mm at the first molars. After the space produced between the upper and lower molars was filled within 10 days due to eruption of the molars, the appliance was removed. In the bite-raised animals, the raised OVD was reduced until it attained that observed in the control animals, after which the OVD increased according to cranial growth. These results show that the OVD is developmentally changed and strictly controlled.

Summary.Aim. The purpose of this study was to present a new visualizing method for temporomandibular joint (TMJ) pathology in 3D at several condylar positions and to apply the method to a case of juvenile chronic arthritis (JCA) with previously diagnosed bilateral TMJ disorder and to a subject without signs and symptoms from the TMJ. Subject. The 20-year-old female patient had suffered from polyarticular JCA from the age of 6 years 8 months. The present study is based on a follow-up examination after the completion of orthodontic treatment with the Herbst appliance. Both TMJs were examined using magnetic resonance imaging (MRI) at closed and open mouth positions. The mandibular condyle, the glenoid fossa and the articular disc were segmented and 3D reconstruction of these structures was carried out. Results. The condyle was characterized by an increased sagittal diameter with osteophyte-like formation at the anterior aspect of the condylar head and flattening of the superior surface. The depth of the glenoid fossa was reduced and the articular eminence was remarkably flat. The articular disc was markedly diminished and posteriorly placed on the condylar head. The distance of the condylar path during mouth opening was reduced and the curvature of the condylar path was quite flat. The disc moved slightly posteriorly on the condylar head and remained in the glenoid fossa during mouth opening. Conclusion. The imaging modality described improves visualization of TMJ morphology and gains insight into the TMJ pathology of the JCA patient, adding to understanding of the clinical problems.

Summary Influence of mandibular asymmetry and cross-bite on temporomandibular joint (TMJ) articulation remained unknown. This study aimed to investigate whether/how the working-side condylar movement irregularity and articular spaces during chewing differ between patients with mandibular asymmetry/cross-bite and control subjects. The cross-bite group and the control group consisted of 10 adult female patients and 10 adult female subjects, respectively. They performed unilateral gum-chewing. The mandibular movements were recorded using a video-based opto-electronic system. The 3D articular surface of the TMJ for each individual was reconstructed using CT/MRI data. For local condylar points, the normalised jerk cost (NJC) towards normal direction to the condylar surface, the angle between tangential velocity vector and condylar long axis and intra-articular space were measured. Three rotatory angles at centre of the condyle were also measured. During closing and intercuspation, (i) movements of posterior portion of the deviated side condyle showed significantly less smoothness as compared with those for the non-deviated side and control subjects, (ii) the rotations of the condyle on the deviated side induced greater intra-articular space at posterior and lateral portions. These findings suggest that chewing on the side of mandibular deviation/cross-bite may cause irregular movement and enlarged intra-articular space at posterior portion of the deviated side condyle.

Galnt3, UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3, transfers N-acetyl-D-galactosamine to serine and threonine residues, initiating mucin type O-glycosylation of proteins. We searched the target genes of Runx2, which is an essential transcription factor for chondrocyte maturation, in chondrocytes and found that Galnt3 expression was up-regulated by Runx2 and severely reduced in Runx2(-/-) cartilaginous skeletons. To investigate the function of Galnt3 in chondrocytes, we generated Galnt3(-/-) mice and chondrocyte-specific Galnt3 transgenic mice under the control of the Col2a1 promoter-enhancer. Galnt3(-/-) mice showed a delay in endochondral ossification and shortened limbs at embryonic day 16.5, suggesting that Galnt3 is involved in chondrocyte maturation. Galnt3 transgenic mice presented dwarfism, the chondrocyte maturation was retarded, the cell cycle in chondrocytes was accelerated, premature chondrocyte apoptosis occurred, and the growth plates were disorganized. The binding of Vicia villosa agglutinin, which recognizes the Tn antigen (GalNAc-O-Ser/Thr), was drastically increased in chondrocytes, and aggrecan (Acan) was highly enriched with Tn antigen. However, safranin O staining, which recognizes glycosaminoglycans (GAGs), and Acan were severely reduced. Chondroitin sulfate was reduced in amount, but the elongation of chondroitin sulfate chains had not been severely disturbed in the isolated GAGs. These findings indicate that overexpression of Galnt3 in chondrocytes caused dwarfism due to the increase of mucin-type O-glycans and the reduction of GAGs, probably through competition with xylosyltransferases, which initiate GAG chains by attaching O-linked xylose to serine residues, suggesting a negative effect of Galnt family proteins on Acan deposition in addition to the positive effect of Galnt3 on chondrocyte maturation.

Response of temporomandibular joint (TMJ) articulation adapting to occlusal alteration has been sparsely known. For 10 healthy adults with acceptably good occlusion, an artificial occlusal interference (OI) was introduced to the lower molar on the balancing side of unilateral chewing. Subjects were asked to chew a gum on their preferred side. The chewing jaw movements with/without the OI were recorded using a video-based optoelectronic system. The mandibular movements were generated in each individual's TMJ model reconstructed by magnetic resonance images. The smoothness of local condylar point movements towards the normal direction of the condylar surface and interarticular space on the working side was measured. Overall, the smoothness of condylar point movements in the closing phase was impaired immediately after introduction of the OI. In the intercuspal phase, the OI increased the joint space. After about 60 chewing cycles, the movement smoothness and joint space began to recover. These findings suggest that OI on the balancing side induced irregular stress field translation on the working-side condylar surface followed by acute recovery process.

This case report examines the masticatory jaw movements and electromyograph (EMG) recordings of anterior and posterior temporal and masseter muscles before and after surgical orthodontic treatment in an adult patient with incisor crossbite and skeletal Class III jaw base relationship. The prescribed treatment resulted in a good occlusion and skeletal and dental Class I relationship. The chopping type jaw movement pattern during gum chewing was transformed to more of a grinding motion after treatment. But this motion was not as broad as is normally seen. This observation is indicative of the difficulties associated with improving the masticatory jaw movements in an adult patient to a completely normal pattern even after retention. In this patient, the high frequency of silent periods on the EMG that were observed in the early intercuspal phase before treatment were decreased to normal low levels after treatment. A similar decrease was also seen in the mean duration of the chewing cycle. We conjecture that this patient unsuccessfully attempted to compensate for the silent periods by increasing the period of his chewing cycle.

To achieve the complete three-dimensional (3-D) data retrieval of the shape of dentition, dental casts were measured from four directions; occlusal, right, left, and labial sides using a line laser scanner. Reconstruction of the entire shape, including undercuts and tooth crowding area, was attempted by applying a perceptual grouping algorithm, which is one of pattern-recognition theories. In the data measured from occlusal, right and left sides, the rows of measurements were parallel to the frontal plane, and three-directionally combined data (3-DC data) was accomplished by affine transformation. While, in the labial side, transformation to the frontal plane was done since rows of the measured data were parallel to the sagittal plane. To combine the labial data with the 3-DC data and reconstruct the complete image, rearrangement of the order of the data in the file was attempted by applying the perceptual grouping. That is, the minimum total length of data combining was examined by considering the factor of proximity and continuity between the data. The most appropriate order of data combining and recognition of islands were accomplished. Using a computer graphic (CG) with a wire-frame model, complicated regions such as anterior segments showing tooth crowding and undercut area were found to be successfully reconstructed without any data defects. The accuracy of reconstruction was ascertained by comparing the characteristic distances between apexes of molars in the reconstructed model with the real cast. The difference was within 0.3 mm, and present method for dental cast reconstruction is considered to be satisfactory for the present purpose such as orthodontics.

The objective of this study was to demonstrate sexual dimorphism in the entire three-dimensional facial surface form of adult humans. The sample consisted of female and male groups (n=200; age range, 18-35 years). Three-dimensional images of each participant's face at rest were recorded. A total of 185 variables that described facial surface configuration features were extracted from each image. The variables were compared between the groups using t-tests, and those exhibiting P-values

An influx of mononuclear cells and the subsequent increase of osteoclasts around tooth germs suggests that the dental follicle (DF) regulates or influences bone resorption required for tooth eruption. In order to study the effects of DF cell products on osteoclast formation during tooth eruption, a conditioned medium (CM) was created in which DF cells were added to mouse bone marrow cultures. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated cells were formed in the presence of 10 nM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The CM, dose-dependently, stimulated the formation of TRAP-positive cells in the presence of 1,25(OH)2D3 for 14 days culture. The number of these cells decreased due to degradation in the control culture. A semi-solid methylcellulose assay in the presence of CM showed little expression of colony-stimulating activity. These results suggest that the DF cells of a developing tooth produce factor(s) that enhance osteoclast formation and bone resorption necessary for tooth eruption.

The regulation by muscle spindles of jaw-closing muscle activity during mastication was evaluated in anesthetized rabbits. Simultaneous records were made of the discharges of muscle spindle units in the mesencephalic trigeminal nucleus, masseter and digastric muscle activity (electromyogram [EMG]), and jaw-movement parameters during cortically induced rhythmic jaw movements. One of three test strips of polyurethane foam, each of a different hardness, was inserted between the opposing molars during the jaw movements. The induced rhythmic jaw movements were crescent shaped and were divided into three phases: jaw-opening, jaw-closing, and power. The firing rate of muscle spindle units during each phase increased after strip application, with a tendency for the spindle discharge to be continuous throughout the entire chewing cycle. However, although the firing rate did not change during the jaw-opening and jaw-closing phases when the strip hardness was altered, the firing rate during the power phase increased in a hardness-dependent manner. In addition, the integrated EMG activity, the duration of the masseteric bursts, and the minimum gape increased with strip hardness. Spindle discharge during the power phase correlated with jaw-closing muscle activity, implying that the change in jaw-closing muscle activity associated with strip hardness was caused by increased spindle discharge produced through insertion of a test strip. The increased firing rate during the other two phases may be involved in a long-latency spindle feedback. This could contribute to matching the spatiotemporal pattern of the central pattern generator to that of the moving jaw.

Orthodontic tooth movement is known to cause pain and discomfort to patients. Mechanically induced inflammatory responses in the periodontium are assumed to be related to the mechanism of pain sensation. An immediate-early gene, c-fos, that is expressed within some neurons following synaptic activation, is widely used as a marker for neuronal activity following noxious or innocuous stimulation. We have recently demonstrated that experimental tooth movement produced Fos induction in the ipsilateral trigeminal subnucleus caudalis and in the bilateral lateral parabrachial nucleus, which is known to be involved in the transmission of nociceptive information. As a further step, we investigated the distribution of Fos-like immunoreactive neurons in the upper brain regions. Twenty-four hours after the commencement of the experimental tooth movement, the Fos-like immunoreactive neurons appeared in the central nucleus of the amygdala (Ce), paraventricular nucleus of the hypothalamus (PVH), and paraventricular nucleus of the thalamus (PV) of the experimental rats. The numbers of the labeled neurons were significantly increased by 639% (P < 0.001) and 644% (P < 0.001) in the ipsilateral and contralateral sides of the Ce, respectively, by 292% (P < 0.001) and 307% (P < 0.001) in the ipsilateral and contralateral sides of the PVH, and by 264% (P < 0.0001) in the PV with respect to sham control rats. These results suggest that nociceptive information caused by experimental tooth movement might be transmitted and modulated in several regions of the forebrain.

Objective: To examine the changes in jaw movement and temporalls muscle activity of a patient with unilateral cleft lip and palate before and after edgewise treatment. Design: Clinical case study. Setting: University dental hospital, department of orthodontics. Patient: A 12-year 3-month-old male with incisor crossbite, molar malocclusion, and repaired unilateral cleft lip and palate who had completed first-phase orthodontic treatment. Main Outcome Measures: This patient was treated with an edgewise appliance. Jaw movement and temporalls muscle activity during the chewing of a hard gummy jelly were recorded at 2 kHz from the sixth to the twentieth stroke before edgewise treatment and after a retention period of 2 years. Results: Optimum intercuspation of teeth was achieved. The reversed crossing jaw-movement pattern before treatment changed to a normal grinding after treatment. The posterior temporalis muscle on the chewing side exhibited an earlier burst than the contralateral one during chewing at the post-treatment stage, as is observed in cases with good occlusion. Conclusion: Improved in the occlusion using an edgewise appliance is necessary for acquiring a good masticatory function in patients with incisor crossbite, molar malocclusion, and cleft lip and palate.

The possible influences of the direction of occlusal loading delivered to the incisors in the sagittal direction during chewing on jaw movement and jaw closing muscle activity were investigated. Ten healthy children with crossbite of one or two incisors on the right side were selected. Each subject chewed a piece of chewing gum on the right side, and jaw displacements and electromyographic signals from the posterior temporalis and superficial masseter muscles on the ipsilateral side were sampled simultaneously. After orthodontic correction of the incisor crossbite relationship, identical records were taken. The inclinations of the gliding contacts for each posterior tooth in the lateral jaw excursion position were consistent before and after the treatment. The posttreatment records showed broader jaw movement patterns in the frontal view and faster jaw movement velocity in the lateral direction at a level close to the habitual maximum intercuspation position, when compared with the pretreatment records (P < 0.05). The duration of the muscle activity and the incidence of the silent periods of the masseter muscle during chewing significantly decreased after the treatment (P < 0.05). The current results give a neurophysiologic rationale for explaining the significance of orthodontic treatment in improving lowered masticatory efficiency in the way that the change in direction of the occlusal load achieved by tooth movement influences on the periodontal sensory input, which, in turn, modifies the trigeminal motor output and thus, eventually, jaw muscle activities. (Am J Orthod Dentofac Orthop 1997;112:403-9.)

This study clarified the neural mechanisms underlying jaw movements in pharyngolaryngeal reflexes such as swallowing in rats. After retrograde tracer injections into the ventromedial division (Vmovm) of the trigeminal motor nucleus (Vmo) containing jaw-opening (JO) motoneurons or into the dorsolateral division (Vmodl) of Vmo containing jaw-closing (JC) motoneurons, JO and JC premotoneurons were labeled with an ipsilateral predominance in the medial and intermediate subnuclei of the rostrocaudal middle two-thirds of the nucleus of the solitary tract (Sol); JC premotoneurons were also in the lateral subnucleus of Sol. After anterograde tracer injections into the Sol, axons were labeled with an ipsilateral predominance in the Vmovm and Vmodl, prominently in the ipsilateral Vmovm. After transganglionic tracer applications to the superior laryngeal nerve (SLN) or the cervical trunk of the glossopharyngeal nerve (GpN-ct), labeled afferents were seen in the medial, intermediate, lateral and interstitial subnuclei of Sol at the rostral three-fourths of Sol, indicating considerable overlap with the JO and JC premotoneurons in the Sol. Double labeling experiments demonstrated contacts between the afferent terminals and the JO and JC premotoneurons. The present study has for the first time revealed the differential distribution of JO and JC premotoneurons in the Sol and features of their projections from the Sol, as well as their connections with SLN and GpN-ct afferent inputs. The JO and JC premotoneurons in the Sol may play an important role in generation and organization of jaw movements in pharyngolaryngeal reflexes evoked by SLN and GpN-ct inputs, such as swallowing.

Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K+channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15–20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN.

Current techniques for investigating the functional roles of masticatory muscles are not suited to explaining subject-specific biomechanical relationship between mandibular movements and masticatory muscle activities. The aims of this study were to estimate the muscle tensions of subject-specific masticatory muscles in dental occlusion through the three-dimensional morphologic changes (3DMCs) of the muscles, and to explain the subject-specific biomechanical relationship between the mandibular movement and the muscle tensions. One healthy adult subject underwent magnetic resonance (MR) scans of the head at mandibular rest position (M0) and maximum intercuspation (M1). Based on the two sets of MR images, the mandibular movement was measured by the position changes of the mental protuberance of the mandible and the muscle tension from M0 to M1 for each masticatory muscle was estimated by its 3DMCs. The results showed the subject-specific biomechanical relationship between the mandibular movement and the muscle tensions, and the mandibular movement could be explained by these related muscle tensions anatomically and functionally.

RUNX2 and SP7 are essential transcription factors for osteoblast differentiation at an early stage. Although RUNX2 inhibits osteoblast differentiation at a late stage, the function of SP7 at the late stage of osteoblast differentiation is not fully elucidated. Thus, we pursued the function of SP7 in osteoblast differentiation. RUNX2 induced Sp7 expression in Runx2−/− calvarial cells. Adenoviral transfer of sh-Sp7 into primary osteoblasts reduced the expression of Alpl, Col1a1, and Bglap2 and mineralization, whereas that of Sp7 reduced Bglap2 expression and mineralization at a late stage of osteoblast differentiation. Sp7 transgenic mice under the control of 2.3 kb Col1a1 promoter showed osteopenia and woven-bone like structure in the cortical bone, which was thin and less mineralized, in a dose-dependent manner. Further, the number of processes in the osteoblasts and osteocytes was reduced. Although the osteoblast density was increased, the bone formation was reduced. The frequency of BrdU incorporation was increased in the osteoblastic cells, while the expression of Col1a1, Spp1, Ibsp, and Bglap2 was reduced. Further, the osteopenia in Sp7 or Runx2 transgenic mice was worsened in Sp7/Runx2 double transgenic mice and the expression of Col1a1 and Bglap2 was reduced. The expression of Sp7 and Runx2 was not increased in Runx2 and Sp7 transgenic mice, respectively. The expression of endogenous Sp7 was increased in Sp7 transgenic mice and Sp7-transduced cells; the introduction of Sp7 activated and sh-Sp7 inhibited Sp7 promoter; and ChIP assay showed the binding of endogenous SP7 in the proximal region of Sp7 promoter. These findings suggest that SP7 and RUNX2 inhibit osteoblast differentiation at a late stage in a manner independent of RUNX2 and SP7, respectively, and SP7 positively regulates its own promoter., PLoS ONE, 7(3), e32364; 2012

OBJECTIVES: (1) To identify any differences in the accuracy of the prediction of the summed widths of unerupted permanent canines and premolars for males vs females and, if differences are identified, (2) to examine the sex differences in the best combination of independent variables and (3) to evaluate the practical accuracy using our models for both sexes, respectively. MATERIALS AND METHODS: Records for 200 orthodontic patients (100 males and 100 females) with discernible tooth crowding in the permanent dentition were selected. Mesiodistal tooth crown widths, dental arch widths, and basal arch lengths were measured. Predicted sum widths of permanent canines and premolars in both dental arches were calculated using stepwise regression analysis. RESULTS: Among male subjects, the best combinations of independent variables were the widths of the upper central and lateral incisors (U1, U2) and the first molar (U6) for the maxilla (R(2) = 0.615) and the mandible, lower central and lateral incisors (L1, L2), and the first molar (L6) (R(2) = 0.685), whereas in females, the best combinations for prediction were found to be U1, U2, U6, and the maxillary arch width for the maxilla (R(2) = 0.429) and L1, L2, L6, and the basal arch length for the mandible (R(2) = 0.426). Correlation coefficients between each independent and dependent variable in the female subject group were found to be weaker than those for the male subject group. CONCLUSIONS: We found the sex differences in the accuracy of prediction and the best combination of independent variables for predicting the summed widths of unerupted canines and premolars. These new models should be clinically useful, providing highly accurate prediction.

OBJECTIVE: To develop a system that automatically recognizes the dentoskeletal traits on cephalograms recorded for preadolescent children and to examine performance reliability. MATERIALS AND METHODS: We obtained 859 lateral cephalograms and divided them into group P (400 films taken from orthodontic patients having permanent dentition) and group M (459 films taken from those having mixed dentition). Fifty-nine cephalograms in group M were reserved for system test, and the remaining cephalograms in groups M and P were used for system development. Using a previously reported method (Yagi and Shibata, 2003), systems S(M) and S(P+M) were developed with the knowledge generated from groups M and P+M (combined sample of groups M and P), respectively. The system S(P) that had been developed for cephalograms of permanent dentition in our previous report was also employed for comparison. To evaluate performance reliability, the systems examined the 59 reserved cephalograms. The areas of each system-identified anatomic structure surrounding the anatomic landmarks and the positions of each system-identified landmark were compared with the norms in the form of confidence ellipses. The success rates were calculated for S(P), S(M), and S(P+M). RESULTS: The systems successfully identified all of the specified anatomic structures in all of the images. The systems S(P), S(M), and S(P+M) determined the landmark positions with a mean success rate of 69% (range, 38–98%), 82% (range, 50–100%), and 82% (range, 58–100%), respectively. CONCLUSIONS: Systems S(M) and S(P+M) were confirmed to be accurate and reliable in recognizing the anatomic features on the cephalograms of preadolescent children.