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It has been reported that GroEL, a heat shock protein (HSP) produced by the representative periodontopathogenic bacterium, Porphyromonas gingivalis, induces inflammation-induced osteoclastogenesis and promotes alveolar bone resorption. In this study, we demonstrated the efficacy of a mucosal vaccine targeting GroEL against bone resorption induced by P. gingivalis. Female BALB/c mice received sublingual CpG oligodeoxynucleotide as an adjuvant with recombinant GroEL (rGroEL) prior to P. gingivalis exposure. Animals were euthanized 30 days after P. gingivalis inoculation. Sublingual immunization (SLI) with rGroEL elicited significant rGroEL-specific serum immunoglobulin (Ig)G and salivary IgA antibody (Ab) responses, and these responses were sustained for approximately 1 year. Interestingly, 10-fold more GroEL-specific IgA Ab-producing cells were detected in the submandibular glands (SMGs) than in the spleen. Antigen (Ag)-specific cells isolated from the spleen and SMGs induced significantly higher levels of IFN-γ expression after Ag restimulation in vitro. Flow cytometry illustrated that the frequency of CD11b

The incidence of pleomorphic adenoma (PA) of the minor salivary glands is reported to be 10%, and while the histological findings in PA can be diverse, keratin-filled cysts lined by squamous epithelium are rarely reported. The condition can, however, present with cyst formation in some cases. We review a rare case of pleomorphic adenoma in the buccal mucosa that involved the formation of multiple squamous epithelium-lined cysts in a 69-year-old woman. Magnetic resonance imaging (MRI), fine needle aspiration cytology, and histopathological examination were performed. Physical examination revealed a painless, mobile, elastic hard mass in the right buccal mucosa, measuring 2.5 × 1.0 cm. The MRI revealed a well-defined lesion with different signal intensities in the medial and distal regions of the right cheek. The medial side of the lesion showed a low signal intensity on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI), while the distal side showed a low signal intensity on T1WI, and a high signal intensity on T2WI and short tau inversion recovery (STIR) imaging. Fine needle aspiration of the lesion was performed under local anesthesia and a cytological diagnosis of an epidermoid or dermoid cyst was made. The tumor was completely resected under local anesthesia combined with intravenous sedation. The histopathological examination demonstrated the proliferation of atypical tumor cells with poor atypia and the formation of glandular, alveolar, large, and small cysts. The cysts were lined by keratinized squamous epithelial cells, their cavities were filled with keratinous material, and foreign body reaction was observed after rupture. Histopathological evaluation led to the diagnosis of pleomorphic adenoma. The patient had no evidence of recurrence, 2 years and 3 months after the surgery. In conclusion, the presence of multiple cysts lined by squamous epithelium can pose a significant diagnostic challenge in patients with PA. It is important to make the correct diagnosis in order to avoid unnecessarily aggressive therapy.

Secreted IgA (SIgA) plays a central role in preventing bacterial and viral infections on mucosal surfaces by neutralizing toxins and viruses and inhibiting bacterial attachment to epithelial cells. However, the role of salivary SIgA antibodies (Abs) in regulating oral flora is still unknown. This study aimed to evaluate the association among oral bacteria, their metabolites and periodontitis in IgA-deficient (IgA KO) and wild-type (WT) control mice. Microcomputed tomography (micro-CT) analysis was used to assess alveolar bone resorption as a development of periodontitis. The bacterial profiles of saliva were determined using the next-generation sequencing assays. Furthermore, the metabolites in saliva were measured and compared using CE-TOFMS. Salivary microbiota of IgA KO mice revealed a remarkably decreased frequency of Streptococcus, and increased percentages of Aggregatibacer, Actinobacillus, and Prevotella at the genus level when compared with those of WT. Compared to WT control mice of the same age, the level of alveolar bone loss was significantly increased in IgA KO mice, and infiltration of osteoclasts was found on the surface of the alveolar bone. The metabolome profile indicated that the metabolites of IgA KO mice had greater variability in carbon metabolic, urea cycle, and lipid pathways than WT mice. These results suggest that salivary SIgA plays an important role in regulating and maintaining normal oral microflora to prevent the development of periodontal disease.

Objective The objective of this study was to evaluate the frequency of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid associated with desquamative gingivitis. Subjects and methods Data from 25 patients were collected by retrospective chart review. Their upper aerodigestive had been evaluated using a conventional flexible fiberscope. Oral disease activity was quantified on the basis of the Mucous Membrane Pemphigoid Disease Area Index activity score. Results Lesions of the upper aerodigestive tract were confirmed in nine symptomatic patients (9/25, 36%), of which five (5/25, 20%) had laryngeal involvement. No lesions were seen in the asymptomatic patients on fiberscope examination. There was a statistically significant difference in the symptoms, high oral disease activity score, and linear IgA deposition on direct immunofluorescence between patients with and without upper aerodigestive tract lesions (p = .001, .001, .002, respectively). Conclusion The high frequency of considerable complications highlights the importance of confirming the presence of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid having desquamative gingivitis. Signs including the presence of symptoms, high oral disease activity score, or linear IgA deposition on direct immunofluorescence might indicate a higher risk of upper aerodigestive tract involvement.

S-1 is an anticancer agent that is comprised of tegafur, gimeracil, and oteracil potassium, and is widely used in various carcinomas including oral squamous cell carcinoma (OSCC). Although an established prediction tool is not available, we aimed to develop prediction models for the sensitivity of primary OSCC cases to the preoperative administration of S-1. We performed DNA microarray analysis of 95 cases with OSCC. Using global gene expression data and the clinical data, we developed two different prediction models, namely, model 1 that comprised the complete response (CR) + the partial response (PR) versus stable disease (SD) + progressive disease (PD), and model 2 that comprised responders versus non-responders. Twelve and 18 genes were designated as feature genes (FGs) in models 1 and 2, respectively, and, of these, six genes were common to both models. The sensitivity was 96.3%, the specificity was 91.2%, and the accuracy was 92.6% for model 1, and the sensitivity was 95.6%, the specificity was 85.2%, and the accuracy was 92.6% for model 2. These models were validated using receiver operating characteristic analysis, and the areas under the curves were 0.967 and 0.949 in models 1 and 2, respectively. The data led to the development of models that can reliably predict the sensitivity of patients with OSCC to the preoperative administration of S-1. The mechanism that regulates S-1 sensitivity remains unclear; however, the prediction models developed provide hope that further functional investigations into the FGs will lead to a greater understanding of drug resistance., Genetics; Clinical Genetics; Surgery; Pharmacology; Oncology; anti-tumor agent; 5-fluorouracil; oral squamous cell carcinoma; OSCC; prediction model; S-1.

Oral squamous cell carcinoma (OSCC) often causes lymphatic metastasis, particularly to the regional cervical lymph nodes. Although lymphatic metastasis is closely associated with lymphangiogenesis in the tumor tissues, the detailed mechanisms are not yet fully understood. The purpose of this study was to examine the morphological association of lymphangiogenesis in the tumor stromal tissue with cervical lymph node metastases in OSCC. The medical records of 13 patients treated for OSCC affecting the tongue at the Department of Oral Surgery of Nihon University School of Dentistry at Matsudo Hospital between November 2003 and March 2011 were reviewed. The 13 cases were divided into two groups, with 7 cases in the metastasis group and 6 cases in the non-metastasis group. Histopathological (hematoxylin-eosin stain) and immunohistochemical (D2-40 antibody) examinations were performed. Lymphatic vascular density and lymphatic vascular area, lymphatic vascular morphology, and the number of lymph vessels were quantified using ImageJ software. The lymphatic vessels in the metastasis group were distributed with higher density and ran irregularly, with more remarkable deformation than those in the non-metastasis group. Cervical lymph node metastasis is one of the factors affecting progression and the prognosis of OSCC patients. In the present study, lymphatic vessels were found in the OSCC stroma, which also suggests that an increased density of lymphatic vessels leads to cervical lymph node metastases.

The nucleus accumbens contains delta-opioid receptors that may decrease inhibitory neurotransmission. As GABA B receptors inhibit dopamine release, decrease in activation of GABA B receptors may be a mediator of delta-opioid receptor-induced accumbal dopamine efflux. If so, accumbal dopamine efflux induced by delta-opioid receptor activation should be suppressed by stimulating GABA B receptors. As delta-opioid receptors are further subdivided into delta1- and delta2-opioid receptors, we analysed the effects of the GABA B receptor agonist baclofen on delta1- and delta2-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds show total amount administered (mol) during 25–50 min infusions. Baclofen (2.5 and 5.0 nmol), which did not alter basal dopamine levels, inhibited the delta1-opioid receptor agonist DPDPE (5.0 nmol)-induced dopamine efflux. Baclofen (2.5 and 5.0 nmol) also inhibited the delta2-opioid receptor agonist deltorphin II (25.0 nmol)-induced dopamine efflux. A low dose of the GABA B receptor antagonist 2-hydroxysaclofen (100.0 pmol), which failed to alter basal accumbal dopamine levels, counteracted the inhibitory effects of baclofen (5.0 nmol) on DPDPE (5.0 nmol)- and deltorphin II (25.0 nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA B receptor-mediated inhibition of accumbal dopaminergic activity facilitates activation of delta1- and delta2-opioid receptor-induced increases in accumbal dopamine efflux. This study suggests that activation of delta1- and delta2-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA B receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux.

Background and purpose This investigation aimed to establish the basis of a pharmacotherapy for nifedipine-induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18-α-glycyrrhetinic acid (18α-GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from patients who presented with nifedipine-induced gingival overgrowth. Experimental approach Gingival fibroblasts were cultured in medium containing 1% FBS with/without 10 μM 18α-GA for 24 or 48 h, and the cell number, cell cycle phase distribution, relative DNA content, apoptotic cell number and morphological characteristics of the cells undergoing apoptosis were measured together with the levels of proteins that regulate these processes and the level of caspase activity. Key results 18α-GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G1 and G0 /G1 phases of the cell cycle and the number of apoptotic cells. Nuclear condensation and fragmentation of cells into small apoptotic bodies appeared in the fibroblasts treated with 18α-GA. In addition, 18α-GA significantly decreased the protein levels of cyclins A and D1, CDKs 2 and 6, phosphorylated Rb (ser(780) and ser(807/811)), Bcl-xL and Bcl-2 and increased the protein levels of p27, cytosolic cytochrome c, pro-caspase-3, and cleaved caspase-3 and the activities of caspases 3 and 9. Conclusions and implications 18α-GA inhibited gingival fibroblast growth by suppressing the G1 /S phase transition and inducing apoptosis. In conclusion, 18α-GA may be used as a pharmacotherapy for nifedipine-induced gingival overgrowth.

Basal cell nevus syndrome, also known as Gorlin–Goltz syndrome, shows five main pathological features: nevoid basal cell carcinomas; keratocystic odontogenic tumours; congenital skeletal anomalies; calcification of the falx cerebri; and point skin depressions on the palms and/or soles. We encountered a 62-year-old man with basal cell nevus syndrome appearing as multiple cystic lesions in the mandible and maxilla, along with bifid ribs. The multiple cystic lesions were identified on panoramic radiography and computed tomography. Bifid rib was apparent at the left eighth rib on postero-anterior radiography and computed tomography. The multiple cystic lesions were removed by an oral surgery team. Histopathological examination diagnosed the specimens as keratocystic odontogenic tumours. Findings were ambiguous regarding the diagnosis of basal cell nevus syndrome, so the patched homologue 1 ( PTCH1 ) gene was sequenced, identifying a novel mutation (1346T → A). These results strongly suggested that the phenotype had been caused by mutations in the PTCH1 gene. The patient was diagnosed with basal cell nevus syndrome based on genetic investigations. In addition, our findings suggest that a novel mutation (1346T → A) may cause osteoplasty of the mandible, maxilla and ribs.

Increasing the efficiency of gene transfer using non-viral vectors, which have the potential to be safe and economical, would improve upon available options for gene therapy. We previously reported that the third EGF motif of the extracellular matrix protein Del1 (E3) increases the transfection efficiency of non-viral vector methods. Here, we asked if E3 could increase the in vivo transfection efficiency of a polyplex-based approach. To test this, cDNA encoding a heat-stable alkaline phosphatase (AP) was first injected intravenously into mice along with recombinant E3. After 24 h, exogenous AP activity in serum was measured. We found that the introduction of E3 resulted in 50 % more AP activity as compared to the control. We next tested transfection into a tumour explant of SCCKN cells, an oral carcinoma-derived cell line. To do this, a cDNA encoding yellow fluorescent protein was locally injected into a tumour explant, followed by local injection of recombinant E3. Use of E3 increased the number of transfected cells to 2.5 times that of the control. Histochemical staining revealed that E3-induced apoptosis in a tumour explant. The data suggest that E3 might be a useful tool for cancer gene therapy using non-viral vectors.

We studied the prevalence of manidipine-induced gingival overgrowth. The incidence of such overgrowth was 1%, and was found in only one case among the surveyed patients. Together with a review of the literature regarding the pathogenesis and clinical management of drug-induced gingival overgrowth, we describe a case of manidipine-induced gingival overgrowth.

We present a case of ethmoid sinus osteoma. A 66-year-old woman was referred with an asymptomatic mass of the nose. Radiographs showed a rounded homogeneous radiodense lesion in the right ethmoid sinus, suggesting an osseous lesion. Computed tomography demonstrated a multi-lobulated high density lesion (2.0×1.5 cm in size) occupying the ethmoid sinus. The lesion was attached to the nasal septum and extended to the posterior orbit. Total excision of the mass lesion was performed under general anesthesia via the oral vestibular approach with an operating microscope. Histopathological examination revealed eburneous-type osteoma. The postoperative course was uneventful.

We report a case of a large calculus in the parotid duct. A 61-year-old man was referred to us with a painless buccal mucosal swelling. Oral examination showed a hemispheric buccal mucosa swelling around the orifice of the parotid duct in the right cheek. The patient denied intermittent swelling and pain of the right parotid gland at mealtime. Salivary secretion was smooth from the orifice and there was no salivary fistula. An oblique radiograph of the right cheek revealed a single, well-defined, homogenous radiopaque mass. Computed tomography scanning showed a high-density mass, round with a 1-cm diameter. The calculus was removed by an oral approach under local anesthesia. The calculus was an irregular globule in shape, 1×1×1 cm in size, and yellowish white in color. Follow-up examination one year later was uneventful.

The concentrations of fluconazole (FLCZ) in serum and mixed saliva after a single intravenous bolus injection of fosfluconazole (504.5mg) were determined by the paper disc method. The samples of serum and mixed saliva were obtained 0.5, 1, 2, 4, 8, and 24 hours after administration. The peak concentrations of FLCZ in serum and mixed saliva occurred 4 hours after administration of fosfluconazole and were 9.45±1.53 and 9.51±2.16μg/ml, respectively. The ratio of the mean concentration ratio of FLCZ in mixed saliva to that in serum was 0.97±0.17. The highest ratio (1.06) was noted 8 hours after administration. There was a significant correlation between the concentration of fluconazole in serum and that in mixed saliva (r=0.8466, p

A rare case of an osteosarcoma of the mandible in a 75-year-old person was reported, and the literature on those 75 years and older were reviewed. The clinical, radiological and histopathological findings were similar to those of cases in younger people. In accordance with an increase in the older population, the number of secondary osteosarcomas has increased, but osteosarcoma of the jawbone in those 75 years and older is still very rare.

Papillary cystadenocarcinoma is an uncommon neoplasm of salivary gland origin that rarely occurs in the major salivary glands. This report describes a rare case of papillary cystadenocarcinoma of submandibular gland origin that was diagnosed on a fine needle aspiration biopsy. A 73-year-old woman was referred to us because of a painless swelling of the submandibular gland. A fine needle aspiration biopsy revealed a malignant tumor of the salivary gland. The submandibular gland containing the tumor was dissected free, together with three associated lymph nodes. The histological diagnosis was papillary cystadenocarcinoma. The postoperative course was uneventful.

Three cases of tuberculous cervical lymphadenitis are presented. All patients presented without positive chest x-ray, fluctuant mass and discharging pus because these cases were all primary and early stage. The diagnoses were very difficult, and histopathological examination was most reliable and only one method.

Haemangioma is a common benign tumour of the oral cavity, with the tongue, lips, and buccal mucous membranes being the most common sites. However, pedunculated haemangioma of the oral cavity is extremely rare. This report is of a 75-year-old woman with pedunculated haemangioma of the hard palate. A 15 × 15 × 5 mm-tumour was found to the right of the hard palate on examination, which increased in size after 2 months to 25 × 20 × 10 mm. The lesion was excised under local anaesthesia. Histopathological examination revealed vascular differentiation, with small and large vascular channels separated by thin-walled vessels, in the tumour. The diagnosis was capillary haemangioma. Interestingly, the tumour displayed a peduncle leading to the hard palate.

A case of a peripheral ameloblastoma of the lower lingual gingiva is reported with a discussion. A 23-year-old woman with epulis- like mass in the lower lingual gingiva was seen in 2001. Excision of the mass was performed and pathological diagnosis of the surgical specimen was peripheral ameloblastoma.