Comparison of Maximum Mouth Opening Following Mandibular Bilateral Sagittal Splitting Ramus osteotomies in Class III Females Using Two Different Osteosynthesis Methods.

BACKGROUND: Limitation of mouth opening is a common complaint following orthognathic surgery. OBJECTIVES: This investigation reports on the progress of maximum incisal opening following orthognathic surgery and compares the impact of two different osteosynthesis methods on mouth opening in female patients with Class III dentofacial deformities. METHODS: Forty cases of skeletal class III malocclusion were divided into twenty cases treated using the conventional single miniplate osteosynthesis method (P1) and twenty cases using the additional L-shaped miniplate osteosynthesis method (P2). No significant differences in pre-operative clinical status were detected between the P1 and P2 group, and all patients were managed with elastics in the post-operative period. Independent mouth opening exercises were initiated seven days after surgery, and inter-incisal distance was measured as maximum mouth opening (MMO) at 1 week, 2 weeks, and 1, 2, 3, 6 months. Statistical analysis was performed in order to analyse differences in MMO between the P1 and P2 groups (Prism 7 GraphPad software, San Diego, CA). Values of P < .05 were considered to be significant. RESULTS: MMO significantly increased from 2 weeks after surgery in both groups. The MMO of P2 was significantly larger than that of P1 in all experimental periods after surgery. MMO was statistically improved in P2 at 2 months after surgery, while MMO in P1 was significantly smaller than the pre-operative MMO, even at 6 months post-operative. A minimum MMO of 40 mm was achieved by all patients. CONCLUSION: L-shaped miniplate osteosynthesis was more useful for early limitation of mandibular opening improvement than conventional single miniplate osteosynthesis.

Proteomic identification of differentially expressed genes during differentiation of cynomolgus monkey (Macaca fascicularis) embryonic stem cells to astrocyte progenitor cells in vitro.

Understanding astrocytogenesis is valuable for the treatment of nervous system disorders, as astrocytes provide structural, metabolic and defense support to neurons, and regulate neurons actively. However, there is limited information about the molecular events associated with the differentiation from primate ES cells to astrocytes. We therefore investigated the differentially expressed proteins in early astrocytogenesis, from cynomolgus monkey ES cells (CMK6 cell line) into astrocyte progenitor (AstP) cells via the formation of primitive neural stem spheres (Day 4), mature neural stem spheres (NSS), and neural stem (NS) cells in vitro, using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS-MS). We identified 66 differentially expressed proteins involved in these five differentiation stages. Together with the results of Western blotting, RT-PCR, and a search of metabolic pathways related to the identified proteins, these results indicated that collapsin response mediator protein 2 (CRMP2), its phosphorylated forms, and cellular retinoic acid binding protein 1 (CRABP1) were upregulated from ES cells to Day 4 and NSS cells, to which differentiation stages apoptosis-associated proteins such as caspases were possibly related; Phosphorylated CRMP2s were further upregulated but CRABP1 was downregulated from NSS cells to NS cells, during which differentiation stage considerable axon guidance proteins for development of growth cones, axon attraction, and repulsion were possibly readied; Nonphosphorylated CRMP2 was downregulated but CRABP1 was re-upregulated from NS cells to AstP cells, in which differentiation stage reorganization of actin cytoskeleton linked to focal adhesion was possibly accompanied. These results provide insight into the molecular basis of early astrocytogenesis in monkey.

Relationship between masticatory ability and physical performance in community-dwelling edentulous older adults wearing complete dentures.

OBJECTIVE: This study aimed to elucidate the association between masticatory ability and physical performance in community-dwelling edentulous older adults wearing complete dentures. BACKGROUND: Physical performance parameters are significant predictors of decreased activities of daily living. Previous studies have shown the relationships between oral conditions and these parameters. Here, we focused on complete denture wearers. METHODS: Two hundred and ten edentulous adults aged ≥65 years and wearing complete dentures were enrolled. The following oral conditions were examined: masticatory ability measured by colour-changing chewing gum, number of foods considered chewable, pain when using dentures and denture base fit. Handgrip strength (HG) and one-leg standing time with eyes open (OLST) were used to evaluate muscle strength and static balance. Spearman's rank correlation coefficients were calculated to examine the correlations between oral conditions and physical performance. Forward stepwise linear regression models were applied with each physical performance parameters as the dependent variable and oral conditions as the independent variable. RESULTS: The women did not show significant correlations between oral conditions and the physical performance. In men, significant and positive correlations were found between the number of chewable foods and HG, and between the colour scores and OLST. The significant correlation between the colour scores and OLST was still noted in the stepwise liner regression analysis after adjusting for demographic, social and medical conditions, and other oral conditions. CONCLUSION: In Japanese elderly edentulous men wearing complete dentures, masticatory ability evaluated as the mixing ability may be associated with static balance.

Analysis of moment structures for assessing relationships among perceived chewing ability, dentition status, muscle strength, and balance in community-dwelling older adults.

OBJECTIVE: The aim of this study was to assess relationships among perceived chewing ability, dentition status, muscle strength and balance in community-dwelling older adults using analysis of moment structures (Amos). BACKGROUND: Physical performance parameters such as muscle strength and balance can predict the future onset of disabilities in activities of daily living among older adults. In this context, elucidation of the relationships among oral conditions and physical performance parameters is necessary. MATERIALS AND METHODS: Data on occlusal contact patterns of natural teeth (OPNT), self-assessed masticatory ability (mastication), body mass index (BMI), handgrip strength (HG) and one-leg standing time with eyes open (OLST) were collected from 501 independently living adults aged 65-74 years. The relationships among these parameters were analysed using Spearman's rank correlation coefficients and Amos. RESULTS: Subjects of both genders showed significant correlations among OPNT, mastication, HG and OLST, evaluated using Spearman's rank correlation coefficients. For each Amos model, the goodness-of-fit statistic indicated a good level of fit. In both men and women, OPNT was significantly related to mastication, and mastication was related to HG but not to OLST. OPNT was related to neither HG nor OLST in women and was related to OLST but not HG in men. CONCLUSION: The findings observed in this study present a possible importance of dental status and perceived chewing ability for the onset of disability by influencing physical performance in community-dwelling older adults.

Tumor endothelial cells acquire drug resistance by MDR1 up-regulation via VEGF signaling in tumor microenvironment.

Tumor endothelial cells (TECs) are therapeutic targets in anti-angiogenic therapy. Contrary to the traditional assumption, TECs can be genetically abnormal and might also acquire drug resistance. In this study, mouse TECs and normal ECs were isolated to investigate the drug resistance of TECs and the mechanism by which it is acquired. TECs were more resistant to paclitaxel with the up-regulation of multidrug resistance (MDR) 1 mRNA, which encodes the P-glycoprotein, compared with normal ECs. Normal human microvascular ECs were cultured in tumor-conditioned medium (CM) and became more resistant to paclitaxel through MDR1 mRNA up-regulation and nuclear translocation of Y-box-binding protein 1, which is an MDR1 transcription factor. Vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and Akt were activated in human microvascular ECs by tumor CM. We observed that tumor CM contained a significantly high level of VEGF. A VEGFR kinase inhibitor, Ki8751, and a phosphatidylinositol 3-kinase-Akt inhibitor, LY294002, blocked tumor CM-induced MDR1 up-regulation. MDR1 up-regulation, via the VEGF-VEGFR pathway in the tumor microenvironment, is one of the mechanisms of drug resistance acquired by TECs. We observed that VEGF secreted from tumors up-regulated MDR1 through the activation of VEGFR2 and Akt. This process is a novel mechanism of the acquisition of drug resistance by TECs in the tumor microenvironment.

Associations between higher-level competence and general intelligence in community-dwelling older adults.

OBJECTIVES: Higher-level competence is crucial for healthy and socially independent living, and general intelligence may underlie heath status. The aim of this study was to elucidate associations between general intelligence and higher-level competence in elderly individuals without dementia. METHODS: A total of 207 community-dwelling elderly persons, aged 70-74 years, were enrolled. A personal interview was performed to obtain data on socio-demographic and medical factors; higher-level competence was evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG index). Raven's Coloured Progressive Matrices (RCPM) test was used to assess general intelligence. Correlations between the TMIG index, its subscale scores and the RCPM score were evaluated by Spearman's rank correlation coefficients. Ordinal regression models were conducted with the TMIG index and its subscales as the dependent variables, RCPM as the principal independent variable, and age, sex, type of household, employment status, educational background, chronic medical conditions and number of natural teeth as the potential independent variables. RESULTS: There were significant but weak positive correlations between total score on the TMIG index, scores on the intellectual activity and social role subscales and RCPM score. In ordinal regression models, RCPM and educational background were significantly associated with total score on the TMIG index and the intellectual activity subscale, and only RCPM was associated with the social role subscale score, after adjusting for other potential variables. CONCLUSION: General intelligence may be significantly associated with higher-level competence, especially with intellectual activity and social role subscales, in community-dwelling older adults.

Relationships between higher-level functional capacity and dental health behaviors in community-dwelling older adults.

OBJECTIVE: The aim of the present study was to elucidate relationships between higher-level functional capacity and dental health behaviours in community-dwelling older adults. BACKGROUND: In ageing society, it is necessary to promote oral health in the elderly, because good oral health is a significant contributing factor to good general health. Higher-level functional capacity has been considered a crucial factor for successful independent living in the elderly. We hypothesised that functional capacity is a significant indicator of dental health behaviours. METHODS: Three hundred and thirty-eight adults aged 65 years or older were enrolled in this study. Higher-level functional capacity was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-index). Univariate and multivariate models were constructed with dental health behaviours, such as regular visits to a dentist, brushing frequency and use of extra cleaning devices, as the dependent variable, and the total TMIG-index score and its subcategory scores as the principal independent variable. RESULTS: Univariate logistic regression analysis demonstrated a significant correlation between low TMIG-index and 'intellectual activity' subcategory scores to lack of regular visits to a dentist and not using extra cleaning devices. Using a multivariate model, significant relationships remained after adjusting for a number of variables including demographics, medical status, lifestyle and number of remaining teeth. CONCLUSION: Intellectual activity of higher-level functional capacity may be an accurate indicator of dental health behaviours in community-dwelling older adults. Intellectual activity should be taken into consideration to effectively promote oral health behaviours and oral hygiene in elderly persons living independently.

Proteomic identification of differentially expressed genes in neural stem cells and neurons differentiated from embryonic stem cells of cynomolgus monkey (Macaca fascicularis) in vitro.

Understanding neurogenesis is valuable for the treatment of nervous system disorders. However, there is currently limited information about the molecular events associated with the transition from primate ES cells to neural cells. We therefore sought to identify the proteins involved in neurogenesis, from Macaca fascicularis ES cells (CMK6 cell line) to neural stem (NS) cells to neurons using two-dimensional gel electrophoresis (2-DE), peptide mass fingerprinting (PMF), and liquid chromatography-tandem mass spectrometry (LC-MS-MS). During the differentiation of highly homogeneous ES cells to NS cells, we identified 17 proteins with increased expression, including fatty acid binding protein 7 (FABP7), collapsin response mediator protein 2 (CRMP2), and cellular retinoic acid binding protein 1 (CRABP1), and seven proteins with decreased expression. In the differentiation of NS cells to neurons, we identified three proteins with increased expression, including CRMP2, and 10 proteins with decreased expression. Of these proteins, FABP7 is a marker of NS cells, CRMP2 is involved in axon guidance, and CRABP1 is thought to regulate retinoic acid access to its nuclear receptors. Western blot analysis confirmed the upregulation of FABP7 and CRABP1 in NS cells, and the upregulation of CRMP2 in NS cells and neurons. RT-PCR results showed that CRMP2 and FABP7 mRNAs were also upregulated in NS cells, while CRABP1 mRNA was unchanged. These results provide insight into the molecular basis of monkey neural differentiation.

A comparison of oral mucositis in allogeneic hematopoietic stem cell transplantation between conventional and reduced-intensity regimens.

Severe oral mucositis developed in allogeneic hematopoietic stem cell transplantation (HSCT) accompanies intolerable pain and risk for systemic bacteremia infection. Conventional stem cell transplantation (CST) and reduced-intensity regimens for allogeneic HSCT (RIST) may differently affect the occurrence and severity of oral mucositis. Here, we comparatively examined oral mucositis in patients undergoing CST and that in RIST patients to search for measures to alleviate oral mucositis. We retrospectively analyzed the data of 130 consecutive patients undergoing HSCT (conventional, 60; RIST, 70). Oral mucositis was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. We also investigated the risk factors for severe oral mucositis in each regimen. The incidence of oral mucositis was not significantly different between RIST and CST patients. The use of opioid analgesics to control pain due to oral mucositis was significantly less in patients undergoing RIST compared with those receiving CST. The risk factors for severe oral mucositis, determined by univariate and multivariate analyses, were "younger age (<40)" in CST and "longer duration of neutropenia (≥ 14 days)" in RIST. Although the incidences of oral mucositis were almost the same, the need for opioid analgesics and the risk factors for severe oral mucositis differed between CST and RIST patients.

Professional oral health care reduces oral mucositis and febrile neutropenia in patients treated with allogeneic bone marrow transplantation.

GOAL OF WORK: Little is known about the effects of professional oral health care (POHC) on the outcome of hematopoietic stem cell transplantation (HSCT). We evaluated the effects of POHC given by dentists and dental hygienists on the development of oral mucositis and febrile neutropenia (FN) after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: We retrospectively studied 140 adult patients who had received allogeneic BMT, with or without POHC, in our hospital consecutively between February 2002 and December 2009. Oral mucositis was evaluated according to the World Health Organization scale. MAIN RESULTS: The incidence of oral mucositis was 66.7% (52/78) in the patients who had received POHC, compared to 93.5% (58/62) in the non-POHC group (P < 0.001). The incidence of FN and the maximal level of CRP were also significantly lower in the POHC group. Multivariate analysis revealed that the POHC was significantly associated with the incidence of oral mucositis (odds ratio, 7.58; 95%CI, 2.45-23.34; P < 0.001). CONCLUSIONS: We concluded that POHC reduced the incidences of oral mucositis and FN by upgrading the overall oral hygiene during HSCT.

Relationship between subjective assessment of oral health and medical expenses in community-dwelling elderly persons.

OBJECTIVES: The increasing medical expenses of elderly persons in Japan's rapidly ageing society have become a major concern. It is therefore important to elucidate the factors associated with such escalation. Here, we focused on the relationship between subjective self-assessment of oral health, as an index of general health, and medical expenses (excluding dental repair) under the hypothesis that oral health contributes to general medical expenses. Several studies have shown that oral health status is correlated with general health status among elderly persons. We speculated that oral health status might show a relation with medical costs among elderly persons. However, few studies have investigated this relationship to date. MATERIALS AND METHODS: Participants were 259 elderly subjects (range: 65-84 years; 120 men, 139 women) residing independently. Subjective assessment of oral health was evaluated by their responses ('Good', 'Not good' and 'Not at all good') on a survey questionnaire. The correlation between subjective assessment of oral health and medical expenditure was analysed using Spearman's rank method, the Mann-Whitney U-test and the Kruskal-Wallis test. Medical expenses were used as the dependent variable in multinomial logistic regression analysis with background and intraoral factors as independent variables. RESULTS: A slight yet statistically significant correlation was observed between subjective assessment of oral health and outpatient treatment fees. CONCLUSION: The findings revealed that subjective assessment of oral health is significantly and independently related to the medical expenses of community-dwelling elderly persons after adjusting for social background, living environment and physical factors.

Relationship between periodontal status and intellectual function among community-dwelling elderly persons.

OBJECTIVE: The aim of this study was to indicate the relationship between periodontal status and intellectual function in the elderly. BACKGROUND: Periodontal status has been shown to be related to demographic, socioeconomic, and psychological status. Intellectual function is a significant indicator of health status. Nevertheless, the relationship between periodontal status and intellectual function has not been elucidated in detail among the elderly. MATERIALS AND METHODS: A total of 152 community-dwelling elderly persons, aged 70-74 years, were enrolled in the study. Periodontal status was evaluated using the WHO Community Periodontal Index of Treatment Needs (CPITN). Intellectual function was assessed by four neuropsychological tests: Raven's Coloured Progressive Matrices (RCPM) test, the Verbal Paired Associates 1 (VerPA) task and the Visual Paired Associates 1 (VirPA) task, extracted from the Wechsler Memory Scale Revised Edition, and the Block Design subtest, extracted from the Wechsler Adult Intelligence Scales, Third Edition. Correlations between CPITN and each test were examined using Spearman rank correlation coefficients. The ordinal regression model was constructed with CPITN as the dependent variable and neuropsychological test as the principal independent variable to adjust for demographic factors, general health, lifestyle and oral health behaviour. RESULTS: Significant correlations were found between the RCPM test, the VerPA task, the Visual Paired Associates 1 and CPITN. In the ordinal regression model, CPITN was significantly related to measures of RCPM after adjusting for demographic factors, general health status, lifestyle and oral health behaviour. CONCLUSION: Intellectual function is considered a significant indicator of periodontal status among community-dwelling elderly persons.

Influence of dental treatment on physical performance in community-dwelling elderly persons.

OBJECTIVE: The aim of the study was to investigate the influence of dental treatment on physical performance (muscle strength and balance function) among the elderly. BACKGROUND: Oral conditions have been associated with physical performance. We hypothesised that improved oral conditions by dental treatment would lead to improved physical performance. METHODS: A total of 154 persons aged 65 years or over were judged to be in need of dental treatment as a result of dental examination; of these, 121 persons underwent dental treatment. After 1 year, differences in each parameter of physical performance before and after the intervention were evaluated using the Wilcoxon signed rank sum test. The Spearman rank correlation coefficient was calculated to examine correlations between changes in self-assessed masticatory ability (masticatory ability) and each parameter of physical performance, and multivariate logistic regression analysis was performed using changes in each parameter of physical performance as the dependent variable and changes in masticatory ability as the principal independent variable. RESULTS: Improved physical performance was not observed for the total study population with dental treatment; however, in subjects with improved masticatory ability, one-leg standing times with eyes open increased significantly. A significant correlation was established between changes in masticatory ability and each parameter of physical performance. These relationships were not found in those without dental treatment. A significant relationship was also established for one-leg standing time after adjusting for age, gender, dentition status and needs of dental treatments. CONCLUSION: Chewing ability may be a positive contributing factor to balance function among the elderly.

Relationships between Geriatric Oral Health Assessment Index scores and general physical status in community-dwelling older adults.

OBJECTIVE: The aim of this study was to investigate the relationships between Geriatric Oral Health Assessment Index (GOHAI) and general physical status among community-dwelling older adults. BACKGROUND: Geriatric Oral Health Assessment Index is a patient-centred assessment of oral health for older adults. We hypothesised that GOHAI is a significant indicator of general physical status of older adults. METHODS: This study included 354 adults (age, ≥65 years) living independently. Body mass index, handgrip strength and one-leg standing time with eyes open were used to evaluate the general physical status. Spearman's rank correlation coefficients were calculated to examine the relationships between the GOHAI scores, its three subdivided categories (physical function, psychological function and pain and discomfort) and each physical status measurement. A stepwise linear regression model was applied with each physical status measurement as the dependent variable and the GOHAI scores and its subdivisions as the principal independent variable. RESULTS: Positive correlations were found between the GOHAI scores, its three subdivided categories and handgrip strength. The physical function category positively correlated with one-leg standing time. The GOHAI and the pain and discomfort category scores were retained in the final models of stepwise regression for handgrip strength, and significant relationships persisted after adjustments for demographic, psychosocial, medical and dental status. CONCLUSION: The GOHAI scores and its pain and discomfort category score may be significant indicators of body muscle strength.

Platinum nanoparticles suppress osteoclastogenesis through scavenging of reactive oxygen species produced in RAW264.7 cells.

Recent research has shown that platinum nanoparticles (nano-Pt) efficiently quench reactive oxygen species (ROS) as a reducing catalyst. ROS have been suggested to regulate receptor activator of NF-κB ligand (RANKL)-stimulated osteoclast differentiation. In the present study, we examined the direct effects of platinum nano-Pt on RANKL-induced osteoclast differentiation of murine pre-osteoclastic RAW 264.7 cells. The effect of the nano-Pt on the number of osteoclasts was measured and their effect on the mRNA expression for osteoclast differentiation was assayed using real-time PCR. Nano-Pt appeared to have a ROS-scavenging activity. Nano-Pt decreased the number of osteoclasts (2+ nuclei) and large osteoclasts (8+ nuclei) in a dose-dependent manner without affecting cell viability. In addition, this agent significantly blocked RANKL-induced mRNA expression of osteoclastic differentiation genes such as c-fms, NFATc1, NFATc2, and DC-STAMP as well as that of osteoclast-specific marker genes including MMP-9, Cath-K, CLC7, ATP6i, CTR, and TRAP. Although nano-Pt attenuated expression of the ROS-producing NOX-family oxidases, Nox1 and Nox4, they up-regulated expression of Nox2, the major Nox enzyme in macrophages. These findings suggest that the nano-Pt inhibit RANKL-stimulated osteoclast differentiation via their ROS scavenging property. The use of nano-Pt as scavengers of ROS that is generated by RANKL may be a novel and innovative therapy for bone diseases.

Analysis of the expression and function of BRINP family genes during neuronal differentiation in mouse embryonic stem cell-derived neural stem cells.

We previously identified a novel family of genes, BRINP1, 2, and 3, that are predominantly and widely expressed in both the central nervous system (CNS) and peripheral nervous system (PNS). In the present study, we analyzed the expression pattern of three BRINP genes during differentiation of mouse embryonic stem (ES) cell-derived neural stem cells (NSCs) and their effects on the cell-cycle regulation of NSCs. While there was no significant expression of any BRINP-mRNA expressed in mouse ES cells, BRINP 1 and 2-mRNAs was expressed at high levels in the ES cell-derived neural stem cells. Upon differentiation into neuronal cells in the presence of retinoic acid and BDNF, all three types of BRINP-mRNA were induced with a similar time course peaking at day three of treatment. Upon differentiation into astroglial cells in the presence of serum, BRINP1-mRNA was slightly up-regulated, while BRINP2- and BRINP3-mRNAs were almost abolished in the astrocytes. While 69.2, 26.1, and 7.7% of cells in a population of NSCs in the exponentially growing phase were in the G1, S and G2 phases, respectively, over-expression of any one of the three BRINP genes completely abolished cells in the G2 phase and significantly reduced the cells in S phase to 11.8-13.8%. Based on these results, the physiological roles of induced BRINP genes in the cell-cycle suppression of terminally differentiated post-mitotic neurons are discussed.

Monocortical mandibular bone grafting for reconstruction of alveolar cleft.

OBJECTIVE: To assess and develop a monocortical mandibular bone grafting procedure for reconstruction of alveolar cleft. DESIGN: Prospective study. SETTING: Hokkaido University Hospital. PATIENTS: Forty-two consecutive Japanese patients who had been treated for a total of 48 clefts according to a strict clinical protocol. Mean age at bone grafting was 6 years 11 months. INTERVENTIONS: Bone grafting was performed by harvesting lateral cortical bone plates from the symphysis and/or body and then placing them on the labial and palatal openings of the alveolar process defect. No particulate bone grafts were packed into the bony cavity. Mean follow-up after bone grafting was 37 months. MAIN OUTCOME MEASURES: Status of the grafted area and eruption of cleft-adjacent teeth were assessed prospectively using computed tomography and periapical radiography. RESULTS: At 6 months postoperatively, computed tomography showed sufficient bone bridge formation at the cleft site in 85.4% of clefts. Periapical radiography showed ≥75% of the root surfaces of cleft-adjacent teeth were covered with spanning bone in 83.3% of clefts. In 92.6% of clefts in which the cleft-adjacent canine was uncovered with bone during follow-up, the canines erupted spontaneously. CONCLUSIONS: Monocortical mandibular bone grafting appears extremely effective for sufficient bone bridge formation and facilitation of cleft-adjacent teeth eruption. The procedure is advantageous in that the quantity of bone required per unit volume of cleft defect is relatively reduced, and larger clefts can thus be treated.

Comparison of Postoperative Stability Between BSSRO and Le Fort 1 Osteotomy with BSSRO in Skeletal Class III Malocclusion with Severe Open Bite.

INTRODUCTION: We aimed to investigate postoperative stability after orthognathic surgery in patients with skeletal class III malocclusion with severe open bite by comparison between bilateral sagittal splitting osteotomy (BSSRO) and BSSRO with Le Fort 1 osteotomy. MATERIALS AND METHODS: Seventeen patients with skeletal class III malocclusion with severe open bite who were needed more than 6 degree counterclockwise rotation of distal segment by only BSSRO in preoperative cephalometric prediction. The subjects were divided into group A, where 9 patients were treated by BSSRO, and group B, where 8 patients were treated by BSSRO with Le Fort 1 osteotomy. Patient's characteristics of age, gender, preoperative over jet (OJ) and over bite (OB) were not found to be significantly different between the two groups. Counterclockwise rotation of distal segment in preoperative cephalometric prediction by only BSSRO was not found to be significantly different between group A of 7.6 (6-10.6) degree and group B of 9 (6-13) degree. The amount of rotation was reduced to 5.4 (3-10) degree by bimaxillary surgery using BSSRO and Le Fort 1 osteotomy in group B. OJ and OB were measured as occlusal stability factor. Distance between ANS-to-PNS plane and the edge of upper incisor (NF-U1Ed), and distance between Menton and edge of lower incisor (Me-L1Ed) were measured as skeletal stability factor using cephalometric analysis. These lengths were measured at pre-surgery (T0), 2 weeks after surgery (T1) and 1 year after surgery (T2), and these differences between the two groups were statistically analyzed. RESULTS: OJ and OB kept a good relation at any experimental periods. The change of Me-L1Ed was significantly larger in group A (1.21 mm at T0-T1, 1.02 mm at T0-T2) than in group B (0.14 mm at T0-T1, 0.16 mm at T0-T2). The change of NF-U1Ed was not significantly different between group A (1.07 mm at T0-T1, 0.57 mm at T0-T2) and group B (0.51 mm at T0-T1, - 0.05 mm at T0-T2). CONCLUSION: In case with more than 6 degree counterclockwise rotation of distal segment, skeletal stability was better after bimaxillary surgery than only BSSRO; however, OJ and OB kept a good relation.

Proteomic identification of differentially expressed genes in mouse neural stem cells and neurons differentiated from embryonic stem cells in vitro.

Embryonic stem (ES) cells are pluripotent stem cells and give rise to a variety of differentiated cell types including neurons. To study a molecular basis for differentiation from ES cells to neural cells, we searched for proteins involved in mouse neurogenesis from ES cells to neural stem (NS) cells and neurons by two-dimensional gel electrophoresis (2-DE) and peptide mass fingerprinting, using highly homogeneous cells differentiated from ES cells in vitro. We newly identified seven proteins with increased expression and one protein with decreased expression from ES cells to NS cells, and eight proteins with decreased expression from NS cells to neurons. Western blot analysis confirmed that a tumor-specific transplantation antigen, HS90B, decreased, and an extracellular matrix and membrane glycoprotein (such as laminin)-binding protein, galectin 1 (LEG1), increased in NS cells, and LEG1 and a cell adhesion receptor, laminin receptor (RSSA), decreased in neurons. The results of RT-PCR showed that mRNA of LEG1 was also up-regulated in NS cells and down-regulated in neurons, implying an important role of LEG1 in regulating the differentiation. The differentially expressed proteins identified here provide insight into the molecular basis of neurogenesis from ES cells to NS cells and neurons.

Multitracer assessment of dopamine function after transplantation of embryonic stem cell-derived neural stem cells in a primate model of Parkinson's disease.

The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)-synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M-1 and M-2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA-specific functions, we used multiple [(11)C]-labeled positron emission tomography (PET) tracers, including [beta-(11)C]L-3,4-dihydroxyphenylalanine (L-[beta-(11)C]DOPA, DA precursor ligand), [(11)C]-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane ([(11)C]beta-CFT, DA transporter ligand) and [(11)C]raclopride (D(2) receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of L-[beta-(11)C]DOPA (M-1:41%, M-2:61%) and [(11)C]beta-CFT (M-1:31%, M-2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M-2 induced reduced [(11)C]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell-based therapies against PD.