Sumio Sakoda

Increased pain sensitivity of the upper extremities of TMD patients with myalgia to experimentally-evoked noxious stimulation: possibility of worsened endogenous opioid systems.

The purpose of this study was to examine whether or not temporomandibular disorder (TMD) patients with chronic masticatory myalgia have increased pain sensitivity at remote sites outside of the head and neck region, and to evaluate whether the endogenous pain inhibitory systems triggered ischemic pain functions favorably in those patients. Twenty female TMD patients with chronic myalgia and 20 controls participated in this study. Ischemic pain was produced to activate endogenous opioids. The pain threshold time, pain tolerance time, pain intensity and pain unpleasantness were compared between the TMD patients and controls. The pressure pain thresholds in the hand were also compared before, between, and immediately after the ischemic pain. The TMD patients showed higher severe pain intensity and unpleasantness values and had lower pressure pain thresholds in the hand. Although both groups showed an increase in the pressure pain threshold, there was less of an increase in the pressure pain threshold in the TMD patients than in the controls. These findings indicate that TMD patients have increased pain sensitivity at remote sites, and also indicate additional evidence that the endogenous opioid systems may become impaired in TMD patients with chronic masticatory myalgia.

An Adult Bimaxillary Protrusion Treated with Corticotomy-Facilitated Orthodontics and Titanium Miniplates

We performed an orthodontic treatment combined with corticotomy and the placement of titanium miniplates in an adult patient who desired a shortened treatment period. The patient had an Angle Class I malocclusion with flaring of the maxillary and mandibular incisors. First, titanium miniplates were placed into the buccal alveolar bone of the maxilla for absolute orthodontic anchorage. Second, an edgewise appliance was applied to the maxillary and mandibular teeth. Then, the maxillary first premolars and mandibular second premolars were extracted. At the same time, a corticotomy was performed on the cortical bone of the lingual and buccal sides in the maxillary anterior as well as the mandibular anterior and posterior regions. Leveling was initiated immediately after the corticotomy. The extraction spaces were closed with conventional orthodontic force (approximately 1 N per side). The edgewise appliance was adjusted once every 2 weeks. The total treatment time was 1 year. Cephalometric superimpositions showed no anchorage loss, and panoramic radiographs showed neither significant reduction in the crest bone height nor marked apical root resorption. A corticotomy-facilitated orthodontic treatment with titanium miniplates might shorten an orthodontic treatment period without any anchorage loss or adverse effects.

NDRG2 is a candidate tumor-suppressor for oral squamous-cell carcinoma

Oral cancer is one of the most common cancers worldwide, and squamous-cell carcinoma (OSCC) is the most common phenotype of oral cancer. Although patients with OSCC have poor survival rates and a high incidence of metastasis, the molecular mechanisms of OSCC development have not yet been elucidated. This study investigated whether N-myc downstream-regulated gene 2 (NDRG2) contributes to the carcinogenesis of OSCC, as NDRG2 is reported to be a candidate tumor-suppressor gene in a wide variety of cancers. The down-regulation of NDRG2 mRNA, which was dependent on promoter methylation, was seen in the majority of OSCC cases and in several cases of precancerous leukoplakia with dysplasia. Induction of NDRG2 expression in an HSC-3/OSCC cell line significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The majority of OSCC cell lines showed an activation of PI3K/Akt signaling, and enforced expression of NDRG2 in HSC-3 cells decreased the level of phosphorylated Akt at Serine 473 (p-Akt). Immunohistochemical p-Akt staining was detected in 56.5% of the OSCC tumors, and 80.4% of the tumors were negative for NDRG2 staining. Moreover, positive p-Akt staining was inversely correlated with decreased NDRG2 expression in OSCC tumors with moderate to poor differentiation (p<0.005). Therefore, NDRG2 is a candidate tumor-suppressor gene for OSCC development and probably contributes to the tumorigenesis of OSCC partly via the modulation of Akt signaling.

Correlation of mandibular bone quality with neurosensory disturbance after sagittal split ramus osteotomy

Our aim was to find out whether the quality of bone around the inferior alveolar nerve is correlated with neurosensory disturbance to the nerve after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Computed tomograms (CT) were taken of 35 patients with mandibular prognathism and 35 without. To assess the density of bone around the inferior alveolar nerve, the width of the buccal cortical bone in the mandibular second molar regions was measured on CT. The Hounsfield units (HU) in the same regions were also measured. The number of HU in the mandible around the second molar regions was significantly higher (p<0.01) in those with neurosensory disturbance (p<0.01). The quality of bone measured by HU is associated with an increased risk of neurosensory disturbance, but the width of buccal bone is not.

Effect of bone quality and position of the inferior alveolar nerve canal in continuous, long-term, neurosensory disturbance after sagittal split ramus osteotomy

OBJECTIVES To examine the relationship between the anatomical position and the bone quality of the inferior alveolar nerve (IFAN) canal and long-term neurosensory disturbance (NSD) of the IFAN after a sagittal split ramus osteotomy (SSRO). MATERIAL AND METHODS CT images were taken of patients with mandibular prognathism. The location of the IFAN and the bone density around the IFAN were measured on CT images. Whether NSD at 6 months and 1 year after SSRO was related to the position and bone quality of the IFAN canal was analyzed. RESULTS Significant correlations were found between the anatomical position and the bone quality of the IFAN canal and the period to the resolution of NSD of the IFAN from 3 months to 1 year after SSRO. If the HU values around the IFAN were greater than 300 HU and/or the distance from the buccal aspect of the IFAN canal to the outer buccal cortical margin was less than 6 mm, NSD of the IFAN at 1 year after SSRO was significantly increased. CONCLUSION It is important to pay particular attention to the anatomical position of the IFAN and the bone quality around the IFAN to predict long-term NSD of the IFAN after SSRO.

Loss of membrane‐bound serine protease inhibitor HAI‐1 induces oral squamous cell carcinoma cells' invasiveness

A loss of balance between cell membrane‐associated proteases and their inhibitors may underlie cancer invasion and metastasis. We analysed the roles of a membrane‐ associated serine protease inhibitor, HAI‐1, in oral squamous cell carcinoma (OSCC). While membranous HAI‐1 was widely observed in cancer cells of human OSCC tissues, this was significantly reduced at the infiltrative invasion front. In vitro, HAI‐1 was detected in all eight OSCC cell lines examined, in which its cognate membrane protease, matriptase was also expressed. HAI‐1 expression knock‐down (KD) in OSCC lines, SAS and HSC‐3, reduced the growth of both lines in vitro but significantly enhanced SAS tumourigenicity in vivo, which was accompanied by histological changes suggestive of the epithelial‐mesenchymal transition. Both HAI‐1‐KD lines also exhibited significantly enhanced migratory capability, and membrane‐associated but not truncated HAI‐1 was required to rescue this phenotype. Other OSCC lines (HSC‐2, Sa3, Ca9‐22) also showed enhanced migration in response to HAI‐1 KD. The enhanced migration is partly attributed to dysregulation of matriptase, as simultaneous matriptase KD alleviated the migration of HAI‐1‐KD cells. HAI‐1 deficiency also altered the expression of CD24, S100A4, CCND2 and DUSP6, all of which are involved in tumour progression. While matriptase was involved in the increased CD24 expression associated with HAI‐1 deficiency, the protease appeared to be not responsible for the altered expression of other genes. Therefore, a matriptase‐independent mechanism for the invasiveness associated with HAI‐1 KD is also present. Together, these observations suggest that HAI‐1 has a crucial suppressive role in OSCC cell invasiveness. Copyright

Overexpression of the DNA sensor proteins, absent in melanoma 2 and interferon-inducible 16, contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation

The development of oral squamous cell carcinoma (OSCC) is a multistep process that requires the accumulation of genetic alterations. To identify genes responsible for OSCC development, we performed high‐density single nucleotide polymorphism array analysis and genome‐wide gene expression profiling on OSCC tumors. These analyses indicated that the absent in melanoma 2 (AIM2) gene and the interferon‐inducible gene 16 (IFI16) mapped to the hematopoietic interferon‐inducible nuclear proteins. The 200‐amino‐acid repeat gene cluster in the amplified region of chromosome 1q23 is overexpressed in OSCC. Both AIM2 and IFI16 are cytoplasmic double‐stranded DNA sensors for innate immunity and act as tumor suppressors in several human cancers. Knockdown of AIM2 or IFI16 in OSCC cells results in the suppression of cell growth and apoptosis, accompanied by the downregulation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells activation. Because all OSCC cell lines have reduced p53 activity, wild‐type p53 was introduced in p53‐deficient OSCC cells. The expression of wild‐type p53 suppressed cell growth and induced apoptosis via suppression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells activity. Finally, the co‐expression of AIM2 and IFI16 significantly enhanced cell growth in p53‐deficient cells; in contrast, the expression of AIM2 and/or IFI16 in cells bearing wild‐type p53 suppressed cell growth. Moreover, AIM2 and IFI16 synergistically enhanced nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling in p53‐deficient cells. Thus, expression of AIM2 and IFI16 may have oncogenic activities in the OSCC cells that have inactivated the p53 system. (Cancer Sci 2012; 103: 782–790)

Lymphoepithelial cyst of oral cavity: Report of a case and review of the literature

A rare case of the oral lymphoepithelial cyst in the ventral surface of the tongue is reported. Histological findings show the same appearance as reported previously, and the continuity of the cyst wall to the oral mucosa in the specimen is suspected. Some aspects of the lesion are reviewed, and its pathogenesis, as reported in the literature, is discussed.

Differential expression of Fos protein after transection of the rat infraorbital nerve in the trigeminal nucleus caudalis.

To determine the effects of nerve injury on Fos expression, temporal and spatial distributions of Fos-positive neurons in the trigeminal nucleus caudalis were examined after tissue injury for isolation of the infraorbital nerve as controls and transection of this nerve as well as noxious chemical stimulation by formalin injection in adult rats. Fos immunoreactivity was markedly elevated in laminae I and II of the only ipsilateral nucleus caudalis 2 h after these surgical procedures and noxious chemical stimulation. The distributions of Fos-positive neurons were restricted rostro-caudally following formalin injection and tissue injury compared to transection of the infraorbital nerve. One day after tissue injury and nerve transection, however, Fos-positive neurons were distributed bilaterally in laminae III and IV extending rostro-caudally and medio-laterally in this nucleus, and this persisted over the 2-week study period. The number of Fos-positive neurons in the side ipsilateral to nerve transection was markedly less than that in the contralateral side whereas positive neurons in the tissue injured rats were distributed symmetrically along the rostro-caudal axis. There was no difference in the contralateral sides between nerve transection and tissue injury groups. The rostro-caudal level showing reduction in Fos expression corresponded roughly to the sites of central termination of the injured nerve in this nucleus, suggesting a role for the primary afferents in the reduction of Fos expression in laminae III and IV neurons of the ipsilateral nucleus caudalis.

Comparison of Material-Related Complications After Bilateral Sagittal Split Mandibular Setback Surgery: Biodegradable Versus Titanium Miniplates

PURPOSE The aim of the present prospective study was to compare material-related complications using biodegradable and titanium miniplates after bilateral sagittal split mandibular setback surgery. PATIENTS AND METHODS The subjects included 200 Japanese adults (67 men and 133 women, age range 18 to 45 years) with jaw deformities diagnosed as mandibular prognathism. All patients were prospectively and consecutively randomized to 2 study groups, receiving biodegradable or titanium fixation plates. Of the 200 patients, 110 underwent bilateral sagittal split ramus osteotomy with a biodegradable fixation plate and 90 underwent bilateral sagittal split ramus osteotomy with a titanium metal plate. The clinical records and radiologic findings of the patients were reviewed, and the incidence of material-related complications was compared. RESULTS The incidence of postoperative complications and breakage in the biodegradable group was 8.2% (9 cases) and in the titanium group was 3.3% (3 cases). No statistically significant difference in the incidence of complications was found between the 2 groups. Fractures of the biodegradable plate occurred at a significantly greater frequency in patients with asymmetry than in patients without asymmetry. CONCLUSION Biodegradable plates were reliable with minimal material-related complications. However, the use of biodegradable plates should be recommended for minimally loaded situations.