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Cytokeratins (CK) are abundant in keratinized cells, particularly CK14 and CK19, which are expressed in stratified squamous epithelial cells. In this study, expression of CK14 and 19 was examined in human epithelial and dysplastic tissues. Surgical specimens from patients with clinically diagnosed oral leukoplakia or early cancer were stained with hematoxylin and eosin and classified into normal, low grade dysplasia (LGD), high grade dysplasia (HGD), or squamous cell carcinoma (SCC). The sections were examined by immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) for CK14 and CK19. Expression and the results of RT-PCR for CK14 showed a decrease in the order of LGD, HGD, and SCC, whereas those of CK19 showed an increase in that order. These results suggest that decreased expression of CK14 and increased expression of CK19 serve as indicators of potential for malignant transformation.

The management of epithelial dysplastic spread around an oral squamous cell carci-noma is very important, particularly intraoperatively. Both cytokeratin (CK) 14 and CK19 are believed to be involved in the development of precancerous lesions, and their expression profiles are quite specific in these and early cancer lesions. Here, expression of CK13, 14, 17, and 19 was investigated in a rat model of 4-nitroquinoline-1-oxide-induced tongue cancer during a series of carcinogenetic processes to determine their value in assessing the features of epithelial dysplastic spread around a cancer. Based on tissue conditions, the results showed that expression levels of CK13 and 14 decreased in the order of no change, dysplasia, and cancer, whereas those of CK17 and 19 increased in the same order. Expression of CK13 showed a significant difference among no change, dysplasia, and cancer. This indicates that comparing the immunohistochemical staining profiles of CKs, especially CK13, could help in assessing the characteristics of epithelial dysplastic spread around a cancer.

The electrical properties of the upper and the lower cancer tissues are about 5 ~ 10 times larger than those of other tissues. These studies have been conducted to detect cervical cancer using the differences in electrical properties, and significant changes in electrical properties have been observed in other organisms when inflammation or dysplasia has occurred. We introduce a new conceptual diagnostic tool that detects the extent, area, and depth of cervical dysplasia and early cervical cancer using noninvasive electrical property measurement and electrical property distribution imaging method and provides clinical diagnostic information.

Objective Maxillo-mandibular advancement (MMA) has attracted attention as a treatment for obstructive sleep apnea syndrome (OSAS) in recent years. We previously evaluated the breathing status during sleep before and after orthognathic surgery and found that maxillary advancement has a greater effect compared with mandibular advancement (J Jaw Deform 2007;17:9–15). The pharyngeal air space, however, exists within the soft tissue surrounded by the jaw bone and the cervical spine, and it can easily be speculated that mandibular advancement will affect its morphology. In this study, changes in the pharyngeal air space before and after periosteal detachment of the inferior and posterior margin of the distal bone fragment of the mandible were investigated. Subjects and methods The subjects were orthognathic surgery patients whose chief complaint was malocclusion. We compared the pharyngeal air space before and after detachment of the periosteum in the same patients. The evaluation method measured the anteroposterior diameter of the pharyngeal air space under endoscopy during anterior traction of the mandible. Results and discussion The anterior range of motion of the mandible increased after the periosteal detachment. Compared with the periosteum before detachment, there was a tendency for the pharyngeal air space not to be enlarged with mandibular advancement after the detachment. These results show that detachment of the periosteum distal bone fragment during mandibular advancement maintains the pharyngeal airway space. Therefore the change would not appear to affect the sleep breathing status.

Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water and bicarbonate toothpaste. However, the effects of an alkaline pH on the oral mucosa had not been elucidated. The purpose of this study was to investigate how basal keratinocytes are actively involved in re-epithelialization after alkaline chemical injury. We generated epithelial defects in the oral mucosa of mice by applying an alkaline chemical, and the localization of cytokeratin 13, cytokeratin 14, PCNA and p63 was investigated during the re-epithelialization process. PCNA- and p63-positive staining was seen in basal cells covering the wound surface at 1 day after the chemical injury. Cytokeratin 14-positive and PCNA-negative basal keratinocytes were localized in a few layers of the wound epithelium during epithelial outgrowth. Cytokeratin 14-positive and PCNA-positive basal keratinocytes, indicating proliferation, were localized over the entire layer of the epithelium at the wound margin. These results imply that basal keratinocytes at the wound margin migrate to the wound surface, provoke differentiation and keratinization during epithelial outgrowth and that epithelial cells are supplied from the wound margin to the epithelial outgrowth after alkaline chemical injury.

Aim It is important to understand dysphagia in patients with dementia, as it is associated with malnutrition and aspiration pneumonia. Particularly in patients with Alzheimer's disease (AD), mortality from pneumonia is high and accounts for 70% of the causes of death. However, the standard swallowing tests are often difficult to use for patients with dementia, and methods to assess daily swallowing function are required. Therefore, the purpose of the present study was to identify signs of dysphagia in AD patients in daily life. Methods A total of 155 AD patients underwent evaluation of their swallowing function (modified water swallowing test), oral status (residual teeth, occlusal contacts), oral functions (lips function, tongue function, rinsing and gargling ability), vital functions (Barthel Index, Vitality Index), nutritional status (serum albumin, body mass index), cognitive function and neurological signs (Mini-Mental State Examination, Clinical Dementia Rating, limb contractures), and diet-related assessments (storing food in the mouth, stuffing food into the mouth, appetite, caloric intake). Results The severity of AD was significantly associated with swallowing function (P

In the pathological diagnosis of oral squamous cell carcinoma, we often confront the difficulty of determining whether it is invasive carcinoma or epithelial dysplasia. Recently, myelin and lymphocyte protein (MAL; T-cell differentiation-related gene) has been reported to be a candidate gene suppressed in esophageal carcinoma. When we performed cDNA microarray analysis, we found that gene expression of MAL was significantly downregulated in oral squamous cell carcinoma (OSCC). We evaluated the expression of the MAL gene by laser microdissection and real-time PCR methods and protein localization by immunohistochemistry. The gene expression of MAL was significantly decreased in OSCC compared with normal epithelium (P < 0.05). Furthermore, protein expression of MAL disappeared gradually in proportion to malignancy. The results suggest that MAL plays an important role during oral carcinogenesis and that the gene may have potential as a biomarker target for OSCC.

OBJECTIVES: To determine the incidence of progressive internal carotid artery (ICA) stenosis by head and neck contrast-enhanced computed tomography (CT) in 82 patients who underwent surgery, chemotherapy, or combination therapy for oral squamous cell carcinoma (OSCC). METHODS: The study included 82 patients who underwent head and neck contrast-enhanced CT after surgery alone or combined surgery and chemotherapy for OSCC at the Department of Oral and Maxillofacial Surgery of Ichikawa General Hospital, Tokyo Dental College, or Tokyo Dental College Oral Cancer Center between December 2002 and March 2010. RESULTS: Comparison with previously obtained head and neck contrast-enhanced CT images revealed progressive arterial stenosis of the ICA in five patients with a mean age of 62.0 years. All five patients were male, and their OSCC sites were the tongue in two, the floor of the mouth in two, and the mandibular gingiva in one. Tumor resection and neck dissection were performed for four patients and tumor resection alone for one patient. Four patients underwent chemotherapy. ICA stenosis occurred on the same side as the tumor in all five patients. CONCLUSIONS: The results of this study suggest that, given the possibility of post-treatment vascular events, attention must be paid to subsequent changes in the ICA over time. The results also indicate the usefulness of head and neck contrast-enhanced CT in identifying such problems.

Radiation-induced xerostomia is a frequent consequence of radiotherapy for head and neck cancer, but its mechanisms remain unclear. Osteopontin (OPN), a highly phosphorylated glycoprotein, has been shown to be involved in the modulation of inflammatory and tissue repair processes and to be expressed in the salivary gland. In this study, using a murine model of radiation-induced xerostomia, expression of OPN in the mouse sublingual gland (SLG) and submandibular gland (SMG) after irradiation was determined by quantitative RT-PCR (qRT-PCR) and western blotting. To explore the cellular location of OPN and its relationships with matrix metalloproteinase 3 (MMP3)-positive and CD11b-positive cells, both of which are also involved in radiation-induced tissue responses, immunofluorescence analysis was performed with anti-OPN, anti-MMP3, and anti-CD11b antibodies. In both the SLG and SMG, a transient increase in OPN mRNA expression was observed on day 5 post-irradiation; this subsequently decreased by day 10 post-irradiation. Western blotting and immunofluorescence analysis revealed downregulation of OPN and MMP3 in duct cells on day 10 post-irradiation, whereas CD11b-positive cells, which were not detected in non-irradiated mice, were increased in the stroma after irradiation. The downregulation of OPN and MMP3, together with the concomitant increase in CD11b-positive cells, may modulate radiation-induced inflammatory responses, resulting in salivary gland dysfunction at a later stage after irradiation.

Aim: In elderly patients with dementia, disturbed eating behavior is understood to be a core symptom or a behavioral and psychological symptom of dementia (BPSD). The purpose of the present study was to investigate the factors affecting self-feeding in elderly patients with Alzheimer's disease (AD). Methods: A total of 150 AD patients who were hospitalized in dementia wards, or were residents of institutions or group homes were enrolled. The patients underwent an eating behavior examination, cognitive assessment, neurological examination and vital function tests. The eating behavior examination consisted of observation of the patients at mealtime. Items assessing eating behavior included the number of feeding cycles, stopping of eating or agitation and dysfunction. Results: Logistic regression analysis carried out to identify factors with a significant effect on decreased independence in eating were difficulty in beginning a meal (OR = 14.498, CI = 2.067–101.690), presence of dysphagia signs (OR = 5.214, CI = 1.031–26.377) and the severity of dementia (OR = 4.538, CI = 1.154–17.843). Conclusion: The present study is the first to generate objective data showing that difficulty in beginning a meal is a factor that hinders independence in eating in AD, in addition to the presence of dysphagia signs and the severity of dementia. Assisting AD patients in maintaining eating independence might be effectively achieved by eliminating environmental factors that interfere with beginning a meal, and by providing assistance that will promote beginning a meal. The present results show the necessity of developing effective methods for assisting elderly patients with AD. Geriatr Gerontol Int 2012; 12: 481–490.

With the founding of its Oral Cancer Center at the Ichikawa General Hospital, Tokyo Dental College established a support system for patients and family members that not only provides surgery and other conventional cancer-oriented treatments, but also palliative care, nutritional support, rehabilitation, and discharge support. With this in mind, the present study sought to examine the nature of support for oral cancer patients with postoperative eating and swallowing disorders by investigating these disorders and identifying their risk factors. The study population comprised 75 surviving oral cancer patients (46 men and 29 women) discharged from the Tokyo Dental College Oral Cancer Center following treatment over a 2-year period from April 2009 to March 2011. Risk factors affecting eating and swallowing function were identified by statistical analysis. Mean age of the patients was 67.3±13.7 years. Fifteen patients had stage I cancer, while 25 had stage II, 13 had stage III, and 22 had stage IV. The feeding route at the time of discharge was oral feeding in 74 patients and a combination of oral and gastrostomy tube feeding in 1 patient. The Tokyo Dental College Ichikawa General Hospital has standardized the expert evaluation and rehabilitation of oral cancer patients with eating and swallowing disorders by establishing a multidisciplinary support system from the preoperative stage onwards. In this context, the results of our analysis of factors influencing the ability of oral cancer patients to orally ingest food after treatment suggest that preoperative cancer stage classification, neck dissection, and tracheotomy are all influential factors. Patients affected by these factors require further multidisciplinary treatment, which in turn necessitates more extensive coordination with other medical professionals and community health care providers.

Against a background of a rapidly aging society, the number of patients with oral cancers in Japan is increasing yearly. The number of double-cancers with oral cancer as the first malignancy is also reportedly on the rise. Esophageal and gastric cancers are the most common second malignancies. At our institution, our policy is to proactively perform upper gastroin- testinal (GI) fiberscopy (GIF) in patients with oral cancer. In anticipation of a probable further increase in the number of patients with double-cancers consisting of oral and GI tract malignancies, we retrospectively analyzed the occurrence of upper GI tract cancers in patients with oral squamous cell carcinoma (OSCC). The cohort consisted of 171 patients in whom OSCC had been diagnosed and who had undergone upper GIF between March 1996 and August 2008. Multivariate analysis was performed. Upper GIF identified 8 patients (7 men, 1 woman, totaling 4.7% of 171 patients) with double-cancer in the upper GI tract. One patient had a triple malignancy consisting of oral, esophageal and gastric cancers. Seven patients had esophageal cancer, while two had gastric cancer. An age of over 65 years was significantly higher in patients with double-cancers including esophageal cancer than in patients without esophageal cancer (OR=10.454, 95% CI=1.143-95.621). None of the other analyzed patient factors (sex, smoking habit, drinking habit, site of OSCC, TNM classification, staging results) showed a significant difference. These results indicate that, when treating elderly patients with oral cancers, physicians need to devise suitable treatment plans which take into account the possibility of upper GI tract cancer, particularly esophageal cancer, as a double-cancer.

The aim of the present study was to investigate the osteogenic capability of rat calvarial periosteal cells in hypoxic conditions in vitro. Periosteum was obtained from the calvarial bone of Sprague-Dawley rats. Following primary tissue culture, subcultured cells were used in hypoxic or normal conditions. On days 1, 2, 3 and 4 following the cell culture, cell proliferation and mRNA and protein expression levels were evaluated. No significant difference in the cell proliferation rate was found between the normal and hypoxic condition groups. The hypoxic condition group exhibited a stronger expression of hypoxia-inducible factor (HIF)1α, vascular endothelial growth factor (VEGF), Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN) and periostin at the mRNA level compared to that of the normal condition group. The hypoxic condition group also exhibited a stronger expression of HIF1α, VEGF, bone morphogenetic protein (BMP)2, Runx2, ALP and BSP at the protein level compared to that of the normal condition group. In conclusion, periosteal cells cultured in hypoxic conditions demonstrated activated osteogenic capability in vitro.

Background: Hyposalivation may affect respiratory disease because the mouth serves as the entrance to the respiratory apparatus, as well as to the digestive tract. Patients with acute respiratory infection generally have a favorable prognosis and a short natural course. However, in cases in which the host has lowered resistance, such as in elderly patients, the infection may develop into pneumonia. Objectives: A prospective study was performed to examine the relationship between hyposalivation, which is common in elderly patients, and acute respiratory infection, which tends to become severe in elderly patients. Methods: The subjects were 323 male and female patients ≥40 years old who lived in Utsunomiya City and surrounding areas and regularly visited the Department of Dentistry and Oral Surgery, Tochigi National Hospital. A 6-month follow-up survey was performed to examine development of acute respiratory infection. Age, sex, and known risk factors were also investigated. Hyposalivation was defined as a saliva production (saliva secretion rate) of ≤0.6 ml/min. Multivariate analysis adjusted for age and sex was performed to examine potential risk factors associated with the development of acute respiratory infection. Results: Data were analyzed for 278 subjects who completed the follow-up survey. The incidence of acute respiratory infection was 60.4%, while hyposalivation was present in 96 subjects (35.5%). Multivariate analysis showed that the incidence of acute respiratory infection was higher in subjects with hyposalivation than in those without hyposalivation (adjusted odds ratio 1.761, p = 0.048). Conclusion: The results of this study suggest that hyposalivation may be a risk factor for acute respiratory infection. This also suggests that improvement of hyposalivation might prevent acute respiratory infection.

Aim: We conducted a survey to investigate the status regarding the implementation of oral health care for inpatients aged 65 years and older who were in the acute stages of stroke and to examine the factors related to the details of excellent model hospitals. Methods: We sent a questionnaire on oral health care targeting all 8089 hospitals in Japan. On the basis of the responses obtained from the hospitals, we conducted a survey to analyze the factors defining what are known to be excellent model hospitals. We then conducted a logistic regression analysis using a stepwise procedure. Results: Replies were received from 2444 of the 8089 hospitals (30.2%): 91.8% of the hospitals reported that oral health care was a part of the daily nursing routine while 91.2% of the hospitals considered that aspiration pneumonia could be prevented by appropriate oral health care. Only 30% of the nurses had undergone oral hygiene training. Among the factors involved in excellent model hospitals, we observed a strong correlation with a sense of the necessity for oral health care, oral hygiene training for nurses and a large number of hospital beds. Conclusion: Large scale hospitals tend to be more interested in oral health care than smaller hospitals. Providing oral health care is already common in acute hospitals in Japan. There is a great demand for oral hygiene training and obtaining information from dental professionals. It is important to promote the cooperation between dental and nursing personnel within hospitals regarding oral hygiene training. Geriatr Gerontol Int 2011; 11: 460–466.

Objective We have searched for the factor to diagnose malignant potential of epithelial dysplasia. Recent studies have suggested that determination of the expression of cytokeratin 13 and 17 would be useful for the early diagnosis of oral squamous cell carcinoma. In this study, we focused on the diagnosis based on the malignant potential of epithelial dysplasia and evaluated the feasibility of combined assessment of cytokeratin 13 and 17. Patients and methods The expression of cytokeratin 13 and 17 observed in 8 patients with clinically diagnosed T1 or T2 tongue squamous cell carcinoma was analyzed using real-time PCR and immunohistochemical staining of resected specimens. Areas in each specimen were identified as Normal, Dysplasia and Cancer. Results Real-time PCR showed that the expression of cytokeratin 13 decreased beginning with Dysplasia, whereas the expression of cytokeratin 17 increased beginning with Dysplasia. Immunohistochemical staining revealed that cytokeratin 13-positive cells decreased beginning with Dysplasia, while there were almost no cytokeratin 13-positive cells in Cancer. Conversely, cytokeratin 17-positive cells increased beginning with Dysplasia, and almost all cells were cytokeratin 17-positive in Cancer. These results thus indicate that the expression of cytokeratin 13 and 17 is associated with carcinogenesis in epithelial dysplasia. Conclusions The findings of this study indicate that assessment of the expression of cytokeratin 13 and 17 might be useful in the diagnosis of malignant potential in epithelial dysplasia. Moreover, evaluating changes in the expression of cytokeratin 13 and 17 could be effective in evaluating surgical margins.

Metals used in the oral cavity have been reported to cause various allergic diseases of the skin and mucosa. Skin manifestations due to dental restorations appear not only in the oral cavity, but also on the hands, feet or the whole body, as in the cases of pustulosis palmoplantaris and lichen planus. These phenomena implicate different pathogeneses from that of conventional skin sensitization and tolerance. Therefore, we compared skin and oral mucosa sensitization with nickel and oral tolerance for nickel in a mouse model. Female C57BL/6J mice were sensitized by injection of NiSO(4) into the skin or oral mucosa. Allergic reactions were evaluated by the mouse ear swelling test and splenocyte proliferation and cytokine profiles. Skin and oral mucosa sensitization succeeded in all mice. Ear swelling was significantly greater in the skin- than in the oral mucosa-sensitized mice at 48 hr after challenge. Ear swelling was also suppressed by single oral administration of NiSO(4) in both the skin- and oral mucosa-sensitized mice to the level of that in nonsensitized mice. Splenocytes from skin-sensitized mice proliferated similarly to those from oral mucosa-sensitized mice. Splenocytes from orally-tolerized mice also showed similar proliferation activity to those from skin and oral mucosa-sensitized mice. In the challenge phase, IL-2, IFN-γ, and IL-10 production was induced in splenocytes from both skin- and oral mucosa-sensitized mice. However, IL-4 was induced only in those from skin-sensitized mice. In addition, IL-4 in splenocytes from oral mucosa-sensitized mice was up-regulated to the level in those from skin-sensitized mice by oral tolerance. These results suggest that sensitization sites in mice influence not only the degree of excitation, but also Th-1 and Th-2 balance in the challenge phase and oral tolerance.

The patch test is the most reliable method for diagnosing a metal allergy. However, interpretation of patch test results depends on the experience of the investigator and on the conditions of the individual patient. In the case of patch tests for metal salts, irritant reactions such as pustular or follicular reactions are quite common. Therefore, one must be careful not to interpret irritant reactions as allergic responses, and objective standards to evaluate erythema in patch tests need to be established. In the present study, we attempted to objectively evaluate patch test results for metal salts using an erythema index meter. We used the Erythema Index Difference (EID) (patch test site erythema index (EI) minus the mean EI of healthy skin outside the patch test area and at the unit tape site) rather than the EI itself in order to eliminate the effects of the patch test unit and individual differences. We measured the EID over time in patients with suspected metal allergies to various metals. Significant differences in EID were observed among ++ assessments, + assessments and irritant reactions based on International Contact Dermatitis Research Group (ICDRG) standards. In considering changes in EID over time, allergic and irritant reactions can be discriminated with high sensitivity (73.3%) and specificity (91.2%). These results suggest that the measurement of erythema over time with an erythema index meter is useful for the objective assessment of metal patch test reactions.

The present study analyzed stress distributions in craniofacial structures around implant-supported maxillary prostheses. Using post-hemimaxillectomy computed tomography (CT) of a patient, the authors constructed a three-dimensional (3D) solid model using Digital Imaging and Communications in Medicine data (DICOM data) for maxillofacial and cranial bones. The effects of different prosthesis designs on stress distributions in craniofacial bones and osseous tissues around the implants were biomechanically investigated using 3D finite-element analysis. Maxillary prostheses were designed with 2 implants in the zygoma on the affected side and 2-3 implants in the maxillary alveolar bone on the unaffected side, without using a cantilever. Zygomatic implants provided suitable stress dispersal to the zygomatic and craniofacial bones on the affected side. This information is useful for designing maxillary prostheses.

We report herein two cases of bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ). Case 1 involved a 72-year-old man diagnosed with osteoporosis who was referred to our clinic for evaluation of swelling of the right mandibular gingiva. Clinical examination revealed a fistulous tract with pus discharge that had developed after extraction of the right mandibular first molar by his dentist. Clinical diagnosis was an infectious bone lesion associated with BP therapy. Risedronate sodium hydrate was administered orally at 2.5 mg/day from July 2005 through April 2007. Radiography revealed osteonecrosis of the jaw and a well-demarcated interface between necrotic and vital bone. BRONJ was completely removed with sequestrectomy of the mandible. The patient has been followed for 9 months since surgery and continues to do well. Case 2 involved a 62-year-old woman diagnosed with bone metastases from breast cancer who was referred to our clinic for evaluation of necrotic bone and pus discharge from the left maxillary molar region. The second maxillary left molar had been extracted by her dentist. Pamidronate sodium hydrate was administered parenterally at 90 mg/month from September 2004 through April 2006, and then zoledronate sodium hydrate at 4 mg/month from May 2006 through October 2007. Radiography revealed osteonecrosis of the jaw and maxillary sinusitis. BRONJ was completely removed with sequestrectomy of the maxilla. The patient has been followed for 5 months since surgery and continues to do well. Surgical intervention thus appears warranted to remove necrotic bone in cases of BRONJ.