Gap junctions are associated with cell growth and differentiation in tissue organization. However, the association of gap junctions with chondrogenesis or chondrogenic differentiation is still unclear. We succeeded in establishing a cartilaginous transplanted tumor in a nude mouse from a human chondroblastic osteosarcoma, and a cell line (USAC) expressing chondrocytic phenotypes from the transplanted tumor. Using these transplanted tumor and USAC cells, we investigated the relationship between the expression of gap junctions and chondrogenesis or chondrogenic differentiation. Gap junctions are observed by immunostaining with connexin 43 (Cx 43) protein, which is an intrinsic component of gap junctions. The results revealed that Cx 43 in the tumor tissue was found both on chondrocytic and hypertrophic cells. In cultured cells, gap junctions composed of Cx 43 appearing as USAC cells were condensed and progressed toward mature chondrocytic cells. A high density micro-mass culture of USAC cells showed that dexamethasone and 1 a, 25 (OH) ₂D₃, which stimulated chondrogenic differentiation, enhanced the expression of Cx 43. These results indicate that expression of gap junctions is closely linked to chondrogenesis and chondrogenic differentiation.

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Lymphatic vessels are distributed directly under the epithelium of the oral mucosal. In the present study, we investigated whether lymphoangiogenseis in tumors occurs in human oral squamous cell carcinoma and whether the density of tumor lympahngiogensis may be related to the risk of lymph node metastasis. Moreover, these analyses identified peritumoral lymphatic vascular density as a novel prognostic indicator for the risk of lymph node metastasis in oral squamous cell carcinoma.
LYVE-1, which was an endothelial cell hyaluronic acid receptor, has been identified as a peculiar protein of endothelial cells of lymphatic vessels. LYVE-1 expression in the carcinoma tissue was divided into two types. In one it appears in contact with the cancer nest. This shows contact with basal-like cells which are located on the outer side of the cancer nest, and observation via light microscope is unable to show intervention of the fibrous connective tissues. The other case is that in which there is intervention of the clear fibrous connective tissues between the cancer nest and LYVE-1-positive cells. The cancer cells showed a high degree of differentiation, increased by the formation of the cancer nest, and in what is called highly-differentiated squamous cell carcinoma whose invasion pattern showed INF alpha, the cells staining positive to the LYVE-1 antibody could be recognized only negligibly in the connective tissue. Positive staining of the LYVE- 1 antibody was seen in the endothelial cells presenting in the lumen formed between each small cancer nest in the case of undifferentiated squamous cell carcinoma in which the cancer nest was very small and composed of undifferentiated cancer cells. In this case the cancer invasion pattern shows INFγ. In addition, the expression of LYVE-1 was recognized in cells which had not formed into the lumen between the cancer nests.
In the meantime, VEGF-C was expressed in endothelial cells which formed the lumen and cancer cells. In the cancer cells which formed the large cancer nest, the expression of VEGF-C was recognized in basal-like cells which located at the periphery of the nest. VEGF-C was expressed in the cancer cells which formed the small nest. The results of this study show that the incidence of VEGF-C expression in the cancer cell is low. However, lymphatic vessels form in carcinoma tissue at a high rate when VEGF-C is expressed. It was shown that in this study, the close proximity of the lymphatic vessel to the cancer nest shows correlation to lymph node metastasis. This should affect the determination of the operation range, and have a direct influence on prognosis. It is also indicated that LYVE-1 can act as a useful marker in oral cancer.

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In skeletal malocclusion cases with marked deformation of maxillofacial morphology, since sufficient functional and esthetic improvement cannot be obtained by orthodontic treatment alone, surgical orthodontic treatment is frequently performed. Therefore, it is important to elucidate the relationship between changes in maxillofacial hard tissue morphology and those in soft tissue when determining the treatment plan.
In this study, regarding the evaluation of frontal facial appearance, which is important from psychological and social aspects, the usefulness of standardized facial photographs was evaluated. Furthermore, the relationship between changes in frontal facial appearance in the standardized photograph and those in hard tissue in frontal and lateral roentgenographic cephalograms after surgery was evaluated.
As a result, after sagittal split ramus osteotomy in skeletal mandibular protrusion cases, the frontal facial appearance became round. Furthermore, it was suggested that mandibular shift with the lateral shift of the proximal bone segment influenced the width, height and symmetry of each facial area, and the inclination of the lips, whereas neither the nasal wing nor the medial angle of the eye was affected. However, our results revealed the limitations of facial photographs. Significant differences after surgery were detected only in part of the measurement items regarding the width and height of the frontal facial appearance, angle in the mental area, SMe deviation, and Go plane when using standardized facial photographs.
Therefore, standardized facial photographs were useful for the evaluation of the measurement items of frontal facial appearance in the horizontal direction. However, it is suggested that the development of new three-dimensional simulation technology is necessary for more precise evaluation.

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Orthodontic treatment planning of the cleft lip and palate vary according to the morphology of the alveolar bone and palatal bone. The purpose of this study is to evaluate the three-dimensional anatomy of the alveolar and palatal bone in children with complete unilateral cleft lip and palate.
Thirty-three nonsyndromic consecutive patients with complete unilateral cleft lip and palate were treated by the cleft palate team at Showa University. Each patient had lip and palate surgeries at Showa University. Cone beam CT radiographs (CB MercuRay, Hitachi) were taken prior to secondary bone grafting, and were classified according to the method of Kita et al. 1997.
Cone beam CT radiographs showed multiple types of alveolar and palatal bone morphology, and focused on special types described in the method of Kita et al.
It was most frequently found that bone defects in the alveolar crest showed similar patterns in both buccal and palatal aspects, and the buccal bone defect in the nasal floor was larger than the palatal bone defect in the nasal floor. In 80% of the patients, the palatal bone defect showed similar patterns in both anterior and posterior aspects, and the anterior palatal bone defect was smaller than the posterior palatal bone defect. In addition, inadequate bone bridges were frequently found at the cleft site.
It is suggested that patients with unilateral cleft lip and palate have various types of alveolar and palatal bone morphology, and are required to take three-dimensional radiographic X-rays prior to any orthodontic treatment.

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The cephalogram and dental cast model are the standard records to evaluate the skeletal/dental relationships of asymmetrical jaw deformities. However, this approach is based on records of different dimensions; such as two-dimensional (2D) cephalograms and dental cast models, so there are some difficulties in making diagnosis with those data. Therefore, this study has two purposes : One is to evaluate the 3-dimensional characteristics of asymmetrical jaw deformities, and the other is to evaluate the relationship between morphological characteristics and the position of the bilateral 1st morlar using 2D cephalograms as 2D measurements and cone beam CT (3DCT) as 3D measurements. The subjects were five mature male patients with skeletal class-3 (C1.3) asymmetrical mandibles shifted to the left-hand side. Linear (n= 9) and angular (n=6) measurements of the maxillofacial bone, based upon conventional craniometric anatomical landmarks (n=9) were taken in 2D and 3D. The results showed three key points as listed below.
1. 3D characteristic : The middle point on the posterior surface of the condyle on the affected side was located at the mesio-exterior side of the saggital facial midplane (N-ANS-PNS).
2. 3D characteristic : The vertex of the gonial angle of the affected side was located at the antero-downward of the saggital facial midplane.
3. Conventional lateral/P-A cephalometric analysis seemed to be affected by the position of the head; such as valuation of the condyle and first molar positions. However, 3D analysis could show the details of each landmark's specific position.
These results indicate that 3D skeletal/dental measurement is an appropriate technique for 3D analysis of maxillofacial deformities, thereby overcoming the limitations of 2D imaging.

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Expression of cyclooxygenase-2 (COX-2) in tumors is known to be associated with enhanced angiogenesis, suppression of host immunity, and tumor invasion. In the present study, human oral squamous cell carcinoma (OSCC) cell lines, NA and HSC-4, were used to evaluate the effects of NS-398, a selective inhibitor of COX-2, and COX-2 antisense oligonucleotide (COX-2 AS) on the invasion activity of OSCC cells. Matrigel invasion assay revealed that the invasiveness of NA and HSC-4 was suppressed by treatment with either NS-398 or COX-2 AS. These reagents also down-regulated the expression and secretion of matrix metalloproteinase-9 (MMP-9). Both ets-1 and ets-2, transcriptional factors of MMP-9, were also down-regulated by treatment with these reagents. Furthermore, phosphorylated c-Fos, a negative regulator of MMP-9, was induced by treatment with either NS-398 or COX-2 AS. These findings suggest that COX-2 selective inhibition, either by NS-398 or COX-2 AS, modulates the transcriptional factors and suppresses the invasiveness of OSCC cells via down-regulation of MMP-9. Genetic or pharmacological inhibition of COX-2 may therefore be a beneficial strategy in the treatment of OSCC patients

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The hydroxyl radical (OH·) has been implicated in the pathogenesis of temporomandibular disorders. In this study, the effects of hydrogen peroxide (H₂O₂) producing OH ? by Fenton reaction on proliferation, cell cycle and apoptosis of a chondrocytic cell line (USAC) were examined.
H₂O₂ inhibited cell proliferation dose-dependently. Catalase and antioxidants such as glutathione ameliorated the inhibitory effects of H₂O₂. However, superoxide dismutase did not exhibit the scavenging activity like catalase. An analysis of cell cycles showed that H₂O₂ decreased the ratio of cells in the G0/G1 phase at the concentration of 50, u M and in the G2/M phase at the concentration of 100, u M, whereas the ratio of S-phase cells increased. The studies on Annexin V staining, morphological observation and caspase-3 activity indicated that H₂O₂ induced apoptosis of USAC.
These results might indicate that the reduction in cell numbers following the addition of H₂O₂ was due to the induction of apoptosis through cell cycle arrest in the G0/G1 and G2/M phases.

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This study was designed to objectively differentiate dysphagic swallow from safe swallow using acoustic characteristics of swallowing and expiratory sounds. Twenty-six postsurgical head and neck cancer patients with swallowing disorder were served as subjects. During VF examination, swallowing sounds and voluntary expiratory sounds after the swallows were detected using our method and fed to a digital video recorder with VF images of these swallows and expiratory events. Acoustic signals of swallowing and expiratory sounds were analyzed by our computed acoustic analyzing system to obtain the duration of swallowing sounds and the averaged revised levels of the six target bands from 63 Hz to 200 Hz of expiratory sounds using the 1/3 octave band analyses. Both 92 swallowing sounds and 46 voluntary expiratory sounds after the swallows were analyzed and compared with the VF findings. Compared with the abnormal group (aspiration or penetration was found on VF image), the safety group without these findings was longer in duration of swallowing sound signals and greater in revised levels of the expiratory sound signals. Zero point eightyeight seconds was set as the critical duration of swallowing sound signals in order to differentiate dysphagic swallows from safe swallows. Seventeen point two dB was also set as the critical revised levels of the expiratory sound signals for differentiating dysphagic from safe swallows. If the both analyzed data of swallowing and expiratory sound signals were over these critical values, the swallows were assessed to be dysphagic. Comparison of these assessments with the differentiations from the VF findings showed significant agreement. Sensitivity was 82.6% (38/46), specificity was 100% (46/46), positive predictive value was 100% (38/38), negative predictive value was 85.2% (46/54) and percent agreement was 91.3% (84/92). These results suggest that duration of the swallowing sounds and revised levels of the expiratory sounds can be used for detecting dysphagic swallow.

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As a department specialized in treating with oral dysfunction, the department of oral rehabilitation was established in Showa University Dental Hospital in June 2004. The clinico-statistical analysis was performed for the aim to investigate the clinical view of registered patients and treatments in this new department from June 2004 to May 2005.
The following results were obtained.
1. The total number of registered patients was 527. The number of 0 to 6 years patients is the most and that of 7 to 12 years patients was second. There was no significant difference of the number between males and females although the dominance of male in forties and that of female over eighties were found.
2. One hundred sixtythree patients were referred from other departments of our dental hospital and 275 patients were referred from other hospitals, clinics, or facilities.
3. Head and neck cancer patients were 16.9%, functional articulation disorder patients 9.1%, and mental retardation patients were 7.8% respectively in the distribution of the primary diseases.
4. Dysphagia was 49.3%, speech disorder 28.5%, and respiratory disorder was 5.3% respectively in the distribution of functional disorders.
5. Swallowing therapy was 36.8%, speech therapy 29.9%, and prosthesis was 9.1% respectively in the distribution of treatment methods.
6. Videofluorography was 106, and respiratory examination for Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) was 22 respectively in the number of examinations.
7. Total number of prosthesis was 84. Maxillary prosthesis was 29.8%, palatal augmentation prosthesis 19.0%, and oral appliance for OSAHS was 19.0%.

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