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Patient A 33-year-old man diagnosed with extranodal natural killer cell/T-cell lymphoma, nasal type (ENKTCL-NT) inducing palatal perforation was referred to the perioperative oral care support center of Tohoku University Hospital for dental care to support cancer treatment including chemotherapy and hematopoietic stem cell transplantation (HSCT). Dental review during chemotherapy revealed mucositis suspected to be caused by mucosal trauma from altered jaw function (chewing and speech) due to palatal perforation. Although the patient was already in the cleanroom, an oral appliance as well as conservative care as recommended in oral management guidelines for HSCT were used to prevent worsening of oral mucositis at subsequent HSCT including High-dose chemotherapy and total body irradiation. After HSCT, a prosthodontist fitted a palatal obturator made by a dental technician and an oral surgeon reviewed the necrotic bone and removed the sequestra according to the changes in the palate. This approach involving a multidisciplinary team including a hematologist improved the impaired oral function and minimized oral complications . Discussion ENKTCL-NT and its treatment have a significant impact on patients' oral status. Hence, it is important to provide customized dental care based on previously endorsed guidelines according to the type of disease, treatment requirements, and oral and systemic status. Conclusions This report indicated the importance of dental care with a customized plan before, during, and after HSCT for ENKTCL-NT with multidisciplinary supportive care for cancer patients to improve the impaired oral function and to minimize oral complications.

One of the most severe complications of lung resection is postoperative pneumonia, and its prevention and prediction are critical. Exhaled acetone and isoprene are thought to be related to metabolism; however, little is known on their relationship with bacteria living in the oral cavity or their meaning in the acute phase in perioperative lung cancer patients. We measured acetone and isoprene in exhaled breath of 13 Japanese patients with lung cancer (3 women and 10 men, age range 62-82 years, mean 72.4 years) before breakfast during hospitalization, and compared with two acute-phase proteins, C-reactive protein (CRP) and albumin in blood serum, as well as the total number of bacteria in saliva and their activity to produce acetone and isoprene. Before operation, intensive oral care was carried out for each patient to prevent postoperative pneumonia, and swallowing and cough reflexes were measured for 12 of 13 patients to assess risk of postoperative pneumonia. Breath and saliva were sampled before intensive oral care (T1), after oral care but before operation (T2), and after operation (T3) during hospitalization. The total number of oral bacteria in saliva decreased significantly from T1 to T2 among 13 patients. No acetone or isoprene was detected from saliva after in vitro incubation under anaerobic or aerobic conditions, but both acetone and isoprene were detected in breath. After operation, breath acetone correlated significantly with CRP (Spearman's ρ = 0.559, P = 0.03), but not with albumin. Breath isoprene correlated significantly with albumin (Spearman's ρ = 0.659, P = 0.008), but not with CRP after operation. Although the number of subjects was small, our results support the hypothesis that breath acetone and isoprene may be related with these acute-phase proteins, which reflect inflammatory reactions and subsequent changes in metabolism in the early postoperative phase of lung resection.

Patients Seventy-one and 73 years-old males visited a perioperative oral care support center to receive perioperative oral management during tongue cancer (T1N0M0) treatment. To improve their quality of life (QOL) during brachytherapy while preventing radiation-related complications including osteoradionecrosis due to 198Au grain brachytherapy, spacers for their maxilla and mandible were designed with consideration of wearing condition at an isolation ward. The spacer was created with unilateral design and with consideration of the tongue mobility during day and night. Then, the spacer was thickened on the plaster model, demonstrating the cancer lesion in the tongue in order to secure the distances from the mandibular body, maxilla and sublingual gland to the radiation sources embedded in the tongue. Discussion Tongue impression made the spacers as small as possible by thickening just around the cancer lesions so that the patients could wear them comfortably, while keeping adequate distance between the radiation sources and peripheral normal tissues. Breakable hard materials were avoided so that the patients were able to utilize the spacers safely without accidentally swallowing a broken fragment. Additionally, considering the upward movement of the tongue in a sleeping posture, the upper spacers were also prepared to protect the maxillae. Computer simulation revealed that the design of our spacers had enough effect on a reduction in radiation to prevent osteoradionecrosis in the maxilla as well as mandibular body. Conclusions This report demonstrated the importance of the spacers created with consideration of patients’ wearing condition to improve their QOL during brachytherapy.

Background Cleft lip and/or palate is among the most prevalent congenital birth defects, and negatively affects maternal psychological status and may consequently result in higher prevalence of child maltreatment. However, the association of childbirths of infants with cleft lip and/or palate with maternal emotional involvement still remains unclear. We examined the association between childbirths of infants with cleft lip and/or palate and mother-to-infant bonding, using data from the Japan Environment and Children’s Study, a nationwide birth cohort study. Methods A cross-sectional study using the jecs-an-20,180,131 dataset was performed. A total 104,065 fetuses in 15 regional centres in Japan were enrolled after obtaining informed written consent. The Mother-to-Infant Bonding Scale, a self-report scale consisting of 10 items, was used to evaluate maternal bonding at one year after childbirth. Finally, the participants consisted of 79,140 mother-infant pairs, of which 211 mothers of infants with cleft lip and/or palate were included in our analyses. Multivariable logistic regression analysis using multiple imputation for missing data was performed to calculate the odds ratio and 95% confidence interval in the estimation of the association between bonding disorders and childbirths with cleft lip and/or palate. Results No increased risk of bonding disorders was observed among all the mothers of infants with cleft lip and/or palate (odds ratio [95% confidence interval]; 0.97 [0.63–1.48], p = 0.880), however, advanced maternal age or multiple parity may adversely affect the associations between bonding disorders and cleft lip and/or palate, respectively. After stratification with a combination of maternal age and parity, a significant association of cleft lip and/or palate with bonding disorders was found only among advanced-age multiparae (odds ratio [95% confidence interval] = 2.51 [1.17–5.37], p = 0.018), but it was weakened after additional adjustment for maternal depression. Conclusions Childbirths of infants with cleft lip and/or palate may increase the risk of bonding disorders among advanced-age multiparae, possibly through maternal depression. This finding provides valuable information for the provision of multidisciplinary cleft care.

Acetaldehyde is a potential carcinogen for esophageal cancer, and some oral microorganisms produce acetaldehyde from ethanol or glucose. In this prospective study, we examined the influence of professional oral care on acetaldehyde levels in mouth air of esophageal cancer patients. Acetaldehyde concentrations in mouth air and breath were measured by a portable gas chromatograph, and acetaldehyde production from oral microbiota was also evaluated. Samples were taken from 21 esophageal cancer patients (median age 68 years) and 20 age-matched healthy volunteers (control group) before and after oral care. Post-operative samples were also taken from 17 patients who had undergone surgery. All samples (mouth air, breath, and saliva) were collected 2 to 3 hours after lunch. Oral microbial samples were prepared from saliva. Genotype analysis of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes revealed no significant differences in the genotypes between the two groups. In the control group, acetaldehyde levels in mouth air showed no significant changes after oral care, while the amount of microbial acetaldehyde production from ethanol was significantly decreased. By contrast, among the patients, acetaldehyde levels in mouth air were significantly decreased after oral care and after operation, while the amount of microbial acetaldehyde production from ethanol showed no significant changes. Moreover, microbial acetaldehyde production from glucose was significantly decreased after operation. Overall, oral health was poorer in the patient group. In conclusion, professional oral care for esophageal cancer patients is effective for reducing acetaldehyde levels in mouth air due to the reduction of microbial count.

Background Since most oral malodor originates from microbial activities in the mouth, the role of microorganisms in producing malodorous gases has been clarified by numerous studies, accompanied by the development of analytical techniques for treatment of halitosis. Highlight Oral microorganisms should be controlled to prevent aspiration pneumonia, especially for elderly perioperative patients. Malodorous gases from the mouth can be an indicator of oral or systemic conditions among patients in intensive care units. Recently, malodorous gases originating from oral microorganisms have been reported as a causal factor in carcinogenesis. Conclusion Further analysis of oral malodor might be useful in accessing the risk of aspiration pneumonia and oral cancer.

The transcription factor Bach2 regulates both acquired and innate immunity at multiple steps, including antibody class switching and regulatory T cell development in activated B and T cells, respectively. However, little is known about the molecular mechanisms of Bach2 regulation in response to signaling of cytokines and antigen. We show here that mammalian target of rapamycin (mTOR) controls Bach2 along B cell differentiation with two distinct mechanisms in pre-B cells. First, mTOR complex 1 (mTORC1) inhibited accumulation of Bach2 protein in nuclei and reduced its stability. Second, mTOR complex 2 (mTORC2) inhibited FoxO1 to reduce Bach2 mRNA expression. Using expression profiling and chromatin immunoprecipitation assay, the Ccnd3 gene, encoding cyclin D3, was identified as a new direct target of Bach2. A proper cell cycle was lost at pre-B and mature B cell stages in Bach2-deficient mice. Furthermore, AZD8055, an mTOR inhibitor, increased class switch recombination in wild-type mature B cells but not in Bach2-deficient cells. These results suggest that the mTOR-Bach2 cascade regulates proper cell cycle arrest in B cells as well as immunoglobulin gene rearrangement.

Background Most bone metastases are observed in the trunk of the body. Metastasis in the mandibular condyle is rare. In many case reports, temporary common temporomandibular joint disorder-like symptoms can be a sign of relapse and metastasis. Case presentation We report a rare case of breast carcinoma metastatic to the left mandibular condyle in a 55-year-old Japanese woman, who visited our department for a dental check-up prior to chemotherapy. She had almost no symptoms, but radiographs suggested the existence of metastasis. Conclusions In many case reports, patients had some symptoms. In this case report, our patient had slight symptoms, but we were able to confirm the metastasis from the symptoms and panoramic dental radiograph. When patients complain about discomfort of the temporomandibular joint, we need to consider the possibility of metastasis and notice changes on the panoramic dental radiograph.

On March 11, 2011, Japan experienced an earthquake of magnitude 9.0 and subsequent enormous tsunamis. This disaster destroyed many coastal cities and caused nearly 20,000 casualties. In the aftermath of the disaster, many tsunami survivors who lost their homes were forced to live in small temporary apartments. Although all tsunami survivors were at risk of deteriorating health, the elderly people were particularly at a great risk with regard to not only their physical health but also their mental health. In the present study, we performed a longitudinal cohort study to investigate and analyze health conditions and cognitive functions at 28, 32, and 42 months after the disaster in the elderly people who were forced to reside in temporary apartments in Kesennuma, a city severely damaged by the tsunamis. The ratio of people considered to be cognitively impaired significantly increased during the research period. On the other hand, the mean scores of the Kessler Psychological Distress Scale-6 and Athens Insomnia Scale improved based on the comparison between the data at 24 and 42 months. The multiple logistic regression analysis revealed that frequency of “out-of-home activities” and “walking duration” were independently associated with an increase in the ratio of people with cognitive impairment. We concluded that the elderly people living in temporary apartments were at a high risk of cognitive impairment and “out-of-home activities” and “walking” could possibly maintain the stability of cognitive functions.

Current understanding of the pathogenic etiology of supra- and subgingival plaque assumes dynamic changes of pathogenic potential depending upon the crosstalk among resident biofilm, as well as that among microbial communities and host tissues, called the ecological plaque hypothesis. Manipulation of bacterial and environmental factors, which affect the proportion and virulence potential, has potential for the control of the pathogenicity of biofilm. Most periodontal pathogens, except Actinobacillus actinomycetemcomitans , are oxygen-sensitive, proteolytic species and are thus unable to survive inside the plaque, which is sufficiently thin to allow oxygen exposure, and also lacks a nutritional supply of protein and some other essential factors. A preventive strategy against these pathogenic microbes would be an ecological approach to maintain health-compatible microflora on the surface of teeth. On the other hand, the strategy against A. acinomycetemcomitans , which is the microbe to which Koch's postulate is most applicable, would be employed in an approach to eliminate this pathogen from the microbial community by use of antibiotics or the humoral immune response of the host. For accomplishing both strategies, we discuss the host–parasite interface, not only the interaction but also the ecological and structural factors, for the purpose of preventing the onset and progression of periodontal diseases.

OBJECTIVES CD14, toll-like receptor 4 (TLR4) and MyD88 have been shown to mediate responsiveness in host cells to lipopolysaccharide. We investigated here the regulatory effects of inflammatory cytokines on the expression of membrane CD14 (mCD14), TLR4 and MyD88, and on subsequent responsiveness to lipopolysaccharide from Actinobacillus actinomycetemcomitans in human gingival fibroblasts. MATERIALS AND METHODS Following treatment with either interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha) or gamma-interferon (IFN-gamma), expression of mCD14/TLR4 and MyD88 was determined by flow cytometry and western blotting, respectively. After pretreatment with IFN-gamma, cells were pre-incubated with either anti-CD14 antibody MY4 or anti-TLR4 antibody HTA125 and subsequently treated with A. actinomycetemcomitans lipopolysaccharide. Then, phosphorylation of mitogen-activated protein (MAP) kinases and IkappaBalpha was examined by western blotting, and production of interleukin-6 and interleukin-8 was measured by their respective enzyme-linked immunosorbent assay (ELISA) kits. RESULTS IFN-gamma stimulated expression of mCD14, whereas -1beta and TNF-alpha did not. Expression of MyD88 but not TLR4 was also enhanced by IFN-gamma. The lipopolysaccharide activated MAP kinases, such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, and IkappaBalpha and stimulated production of interleukin-6 and interleukin-8. The lipopolysaccharide-stimulated interleukin-6 and interleukin-8 production was markedly inhibited by MY4 or HTA125. Pretreatment with IFN-gamma augmented the following activation of MAP kinases and IkappaBalpha and production of interleukin-6 and interleukin-8 in response to the lipopolysaccharide. CONCLUSIONS These results suggest that the augmentation by IFN-gamma of the responsiveness to A. actinomycetemcomitans lipopolysaccharide, such as activation of MAP kinases and IkappaBalpha and terminal cytokine production in human gingival fibroblasts, may be partially mediated by up-regulation of CD14 and MyD88 expression.

Human papillomavirus type 16 (HPV16), a causative agent of cervical cancers, encodes the E6 and E7 oncogenes, whose simultaneous expression is pivotal for malignant transformation and maintenance of malignant phenotypes. In the hope of developing a gene-specific therapy for HPV-related cancer, we examined the effects of E6 short-interfering RNA (siRNA) on the expression of these oncogenes and on the cell growth of HPV16-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that E6 siRNA decreased the levels of mRNA encoding E6 as well as that encoding E7 protein and also induced nuclear accumulation of p53, the most important target of E6. E6 siRNA suppressed monolayer and anchorage-independent growth of SiHa cells, which was associated with p21(CIP1/WAF1) induction and hypophosphorylation of retinoblastoma protein. Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA. Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.

Objectives and background: Endothelin-1 (ET-1) is a 21-amino acid peptide with multifunctional regulation. ET-1 expresses in various cells during inflammation. The present study aimed to examine the ET-1 expression in oral epithelial cells after infection with the periodontal pathogen and to investigate the presence of ET-1 in human inflamed and uninflamed gingival tissues. Materials and methods: The KB cells were infected with Porphyromonas gingivalis and the expression level of ET-1 was examined using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The immunohistochemical analysis of ET-1 was performed in gingival tissues obtained from patients. In addition, the ET-1 mRNA expression in each tissue was also investigated by RT-PCR. Results: The expression of ET-1 in KB cells was strongly induced by the P. gingivalis infection. On the other hand, the strong immunoreactivity for ET-1 was observed in the epithelium and vascular endothelial cells of the inflamed gingival tissue. Furthermore, the level of ET-1 mRNA was greater in the inflamed tissues. Conclusion: These results suggested that the expression level of ET-1 in gingival epithelial cells might be enhanced during the periodontal inflammation.

Bone morphogenetic proteins, including growth/differentiation factor-5 (GDF-5), are multifunctional cytokines. Recent studies of intracellular signal transduction mechanisms for the transforming growth factor-beta superfamily have focused on Smad proteins. However, scant attention has been given to the mechanism by which GDF-5 exerts its negative growth effect on immunological competent cells. In the present study, we demonstrated that GDF-5 induced cell cycle arrest in the G1 phase before the appearance of apoptosis in mouse B cell hybridoma HS-72 cells, while the ectopic expression of Smad6 and Smad7 in HS-72 cells suppressed the GDF-5-induced G1 cell cycle arrest by abolishing the expression of p21(CIP-1/WAF-1) and hypophosphorylation of retinoblastoma protein. Moreover, we found that Smad6 and Smad7 suppressed GDF-5-induced apoptosis in HS-72 cells. These findings indicated that Smad6 and Smad7 exhibit inhibitory effects toward GDF-5-mediated signaling in B lineage cells.

Recent studies have revealed that both transforming growth factor-beta (TGF-beta) and activin A play pivotal roles in osteoclastogenesis. In this report, we show that the effect of TGF-beta family members, TGF-beta1 and activin A, but not BMP-2, enhance multinucleated osteoclast-like cell (OCL) formation induced by receptor activator of NF-kappaB ligand (RANKL) in isolated bone marrow macrophages and monocytic cell line, RAW264.7. TGF-beta1 and activin A caused the growth suppression and concomitant expression of tartrate-resistant acid phosphatase (TRAP) and c-Src, without inducing syncytium formation or increasing the survival rate in RAW264.7 cells. Although TGF-beta1 and activin A had no effect on NF-kappaB and JNK activities, these factors enhanced the expression of JunB, a component of the AP-1 transcriptional complex. These results suggest that TGF-beta1 and activin A may function as commitment factors in osteoclastic differentiation, not as a crucial component for terminal differentiation to form multinucleated OCLs nor in OCL survival.

BMPs exert a negative growth effect on various types of cells. We have previously reported that BMP-2 inhibited the growth of HS-72 mouse hybridoma cells by inducing p21(CIP1/WAF1) expression. In the present study, we demonstrated that BMP-2 activated the mouse p21(CIP1/WAF1) promoter in HS-72 cells, and that a 29-base pair (b) region of the promoter (-1928/-1900 relative to the TATA box), conserved between mice and humans, was responsive to BMP-2 as well as expression of Smad1, Smad4, and constitutively active mutants of BMP type I receptors. Furthermore, an oligonucleotide containing the 29-b region was found to be associated with Smad4 and phosphorylated Smad1 in the nuclear extract of BMP-2-stimulated HS-72 cells. These results suggested that BMP-2 might activate p21(CIP1/WAF1) transcription by inducing a binding of Smad4 and Smad1 to the 29-b region in HS-72 cells.

Infection of murine macrophages in vitro with periodontopathic bacterium Actinobacillus actinomycetemcomitans induces apoptotic cell death. In this study, we investigated the involvement of caspases in apoptotic cell death of A. actinomycetemcomitans-infected macrophages. Two peptide inhibitors of caspases, benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) and benzyloxycarbonyl-Asp-Glu-Val-Asp (OMe)-fluoromethyl ketone (Z-DEVD-FMK), inhibited apoptotic cell death of murine macrophage cell line J774.1 infected with A. actinomycetemcomitans. During the process of apoptosis, interleukin-1beta (IL-1beta) was detected in the culture supernatants of J774.1 cells. IL-1beta secretion was blocked by the caspase-1 inhibitor, Z-VAD-FMK, indicating that caspase-1 is involved in not only the induction of apoptosis but also the IL-1beta secretion from A. actinomycetemcomitans-infected J774.1 cells. Immunoblot analysis revealed that the infection of A. actinomycetemcomitans to J774.1 cells induced the cleavage of retinoblastoma protein (Rb), suggesting that caspase-3 was activated by A. actinomycetemcomitans infection. The cytosol from A. actinomycetemcomitans-infected J774.1 cells induced Rb proteolysis in vitro, which was inhibited by the caspase-3 inhibitor, Z-DEVD-FMK. Furthermore, caspase-3-like activity was markedly increased in J774.1 cells infected with A.actinomycetemcomitans between 12 h and 24 h, which was subsequently inhibited by the addition of caspase-3 inhibitor, Z-DEVD-FMK. These findings indicate that caspase-3 induces apoptosis in J774.1 cells infected with A. actinomycetemcomitans. Taken together, these results suggest that caspase-1 and caspase-3 are involved in the induction of apoptosis in A. actinomycetemcomitans-infected macrophages.

Osteoclasts, bone-resorbing multinucleated cells, develop from monocyte-macrophage lineage cells in the presence of osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) and macrophage colony-stimulating factor (M-CSF). M-CSF-dependent bone marrow macrophages (M-BMMPhis) from mouse bone marrow cells have been shown to differentiate into osteoclast-like multinucleated cells (OCLs) in the presence of soluble ODF/RANKL (sODF/RANKL) and M-CSF within 3 days. In this study, we found that stimulation of M-BMMPhis with sODF/RANKL induced a transient expression of cyclin-dependent kinase inhibitors (CDK inhibitors) p21(WAF1/CIP1) and p27(KIP1) by 24 h. The CDK inhibitor proteins disappeared by 48 h. Tumor necrosis factor alpha (TNF-alpha), which is reported to stimulate OCL differentiation, stimulated p21(WAF1/CIP1) and p27(KIP1) expression in M-BMMPhis as well. However, M-CSF alone did not stimulate the expression of the two CDK inhibitors. To clarify the role of p21(WAF1/CIP1) and p27(KIP1) in osteoclastogenesis, accumulation of these CDK inhibitors was aborted by antisense oligonucleotides. Treatment with p21(WAF1/CIP1) antisense oligonucleotide alone, or p27(KIP1) antisense oligonucleotide alone, showed a limited inhibitory effect on OCL formation. However, treatment with a mixture of these two antisense oligonucleotides strongly inhibited OCL formation. These results suggest that a combined modulation of the CDK inhibitors p21(WAF1/CIP1) and p27(KIP1) may be involved in osteoclast differentiation induced by ODF/RANKL.

Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)–β superfamily, are a group of related proteins that are capable of inducing the formation of cartilage and bone but are now regarded as multifunctional cytokines. We show in this report a novel function of BMPs in hematopoietic cells: BMP-2 induces apoptosis not only in human myeloma cell lines (U266, RPMI 8226, HS-Sultan, IM-9, OPM-2, and KMS-12 cells), but also in primary samples from patients with multiple myeloma. The mechanism of BMP-2–induced apoptosis was investigated with the use of U266 cells, which are dependent on the interleukin-6 autocrine loop. We showed that BMP-2 caused cell-cycle arrest in the G1 phase and the subsequent apoptosis of myeloma cells. BMP-2 up-regulated the expression of cyclin-dependent kinase inhibitors (p21CIP1/WAF1 and p27KIP1) and caused hypophosphorylation of retinoblastoma (Rb) protein. In studies of apoptosis-associated proteins, BMP-2 was seen to down-regulate the expression of Bcl-xL; however, BMP-2 had no effects on the expression of Bcl-2, Bax, or Bad. Therefore, BMP-2 induces apoptosis in various human myeloma cells by means of the down-regulation of Bcl-xL and by cell-cycle arrest through the up-regulation of p21CIP1/WAF1 and p27KIP1 and by the hypophosphorylation of Rb. Further analysis showed that the signal transducer and activator of transcription 3 (STAT3) was inactivated immediately after BMP-2 treatment. We conclude that BMP-2 would be useful as a novel therapeutic agent in the treatment of multiple myeloma both by means of its antitumor effect of inducing apoptotis and through its original bone-inducing activity, because bone lesions are frequently seen in myeloma patients.

B-1 cells are physically and functionally unique B cells that produce polyreactive natural antibody. This study examined the activation of B-1 cells in inflamed gingival tissue. Serum IgG antibodies to phosphorylcholine, E. coli LPS, DNA, and some commensal bacteria were examined in adult periodontitis patients and healthy subjects. In addition, the proportion of B-1a (CD20+CD5+) cells and the amount of IL-6 and IL-10 in the inflamed gingival tissues were examined. The serum levels of IgG antibodies to phosphorylcholine, E. coli LPS, and commensal bacteria were significantly higher in the adult periodontitis patients than the healthy subjects. The proportion of B-1a cells and the amount of IL-6 and IL-10 were significantly higher in the inflamed gingival tissues than in peripheral blood from the healthy subjects. These results suggest the activation of B-1 cells in the inflamed gingival tissue of adult periodontitis patients, and that B-1 cells may serve as the first line of defense by producing polyreactive antibodies to phosphorylcholine, LPS, and commensal bacteria.

Objectives To identify factors associated with dry mouth. Background Dry mouth adversely affects oropharyngeal health, particularly in elderly, and can lead to pneumonia. A better understanding of the epidemiology of dry mouth is therefore important in improving treatment strategies and oral health in high-risk elderly patients. Methods We conducted a cross-sectional study involving 383 dependent Japanese elderly individuals (65–84 [n = 167] and ≥85 [n = 216] years) at eight long-term care facilities and hospitals. Thirty-four potential factors associated with dry mouth were examined by multiple logistic regression analysis. The primary outcome was dry mouth, as diagnosed by tongue dorsum moisture. Results We identified that body mass index and severity of physical disability were identified as a potential factors associated with dry mouth in the super-elderly (≥85 years) group, whereas severity of physical disability, outcome measurement time, high daily water consumption, mouth breathing, use of antidepressants and diuretics, and high frequency of daily brushing (≥2 times per day; Odds ratio: 5.56; 95% Confidence Interval: 1.52–20.00) were associated with dry mouth in the 65- to 84-year-old group. Conclusion To our knowledge, this is the first study to identify a link between frequency of daily brushing and dry mouth and suggests that tooth brushing should be encouraged in high-risk dependent Japanese elderly (65–84 years), particularly those taking antidepressants and/or diuretics.

Oral health care is important for the acute hospitalized patients, to avoid and reduce negative effects or discomfort during the intensive medical care and burdensome medical treatment. It was reported by a questionnaire survey that oral health care was performed by nurses and careworkers in almost all hospitals in Sendai city, except some specialized functional facilities. Also, the collaborations with the dental offices were conducted in about two thirds of the hospitals. The major problems which interfered with the oral health care in hospitals were serious shortage of manpower, inadequate medical and technical service payment, and the lack of experienced stuffs. These problems might be caused by the lack of information and supervision from the dental professions on site in hospitals. To promote and reinforce the oral health care in hospitals, further close and community-based ­collaboration between the hospitals and the neighboring dental clinics are necessary.

In this study, we administered EGCG to MRL/lpr mice from age of 8–16 weeks for 57 days, and thereafter examined immunohistochemically the expression of thymidine glycol (TG), heme oxygenase-1 (HO-1) and ssDNA in autoimmune sialadenitis of submandibular glands of ten EGCG-administered MRL/lpr mice compared with those of six no EGCG-conspecifics controls using streptavidin-biotin methods. TG is formed in nuclei when ROS oxidizes deoxy thymidine and HO-1, one of antioxidants, is induced by green tea catechin. We found that EGCG-administered MRL/lpr mice showed attenuated expression of TG and ssDNA and enhanced HO-1 immunostaining in salivary gland duct epithelial cells. Furthermore, the significant positive correlation existed between TG and ssDNA expression, and the significant inverse correlation was noticed between TG and HO-1 expression. In conclusion, our results indicate that EGCG ameliorates the detrimental influences of oxidative stress on salivary gland tissues in autoimmune sialadenitis of MRL/lpr mice.

To provide the intensive oral care to the hospitalized and home-care patients, we discuss the current status and improving measures of promoting oral care in Sendai city. The questionnaire survey among the dentists who are working at the dental offices, revealed that one-fourth of the dentists has experiences of visiting to the patient home, other medical facilities, and the nursing homes for the elderly. Half of the dentists who had no experiences to visit patients out of their dental offices, considered that they had prepared ready to go out from their offices by the requests for oral care on demand. To promote the professional oral care for the hospitalized and home-care patients, it would be helpful to open the liaison offices to share information and to collaborate between the medical and dental facilities each other about the needs of oral care.

In aging society, the life of elderly people should be brighten and be enriched by supporting and maintaining a high standard of their quality of life (QOL). Especially in nursing home, the level of QOL of the residents should be maintained regardless their disability or the degree of care necessary. From our analysis of questionnaire and assessment of the facility-users and care-providers, we proposed an oral health care model referring Maslow’s hierarchy of needs. This model represents the role of oral health care to achieve self-esteem and self-actualization of both facility-users and care-providers. Promoting oral health care in nursing home might create hospitable and humanized workplace and living place. Furthermore, the proposed oral health care model would construct more integrated relation between facility-users and care-givers, and it would provide well-being to both, with high standard of QOL.

Probing to detect calculus on root surfaces in periodontal pockets is the most common and gold-standard technique for the diagnosis and evaluation of treatments of periodontal diseases. However, root surfaces with calculus are always atypical and it is very difficult to identify the exact location of invisible calculus within periodontal pockets. Periodontal probing also encompasses inherent measurement errors from a wide range of clinical source. The average probing forces pushing laterally and axially against the tooth model were significantly gentle in the trained examinees, who identified the two test shape, compared with unpracticed group who identified only one shape. For the accurate detection of the morphology of root surfaces, the optimal lateral and axial probing forces on the probe tip are suggested to be around 20 gramF and examinee might need to take time to concentrate sophisticated and delicate sensing. We need to develop the suitable methods to teach these sophisticated skills in early dental practical educations.

Difference of breath acetone between type 1 and type 2 diabetes mellitus (DM) is examined under informed consent. We measure acetone in mouth air and in deep breath by Gas Analyzer® XG-100V (New Cosmos Electric Co., Ltd., Osaka, Japan) and volatile sulfide compound in mouth air by Breathtron® (New Cosmos Electric Co., Ltd., Osaka, Japan), after meal. The acetone ratio of deep exhaled breath to mouth air and concentration of volatile sulfide compound (VSC) are compared between type 1 and type 2 DM patients. The acetone ratio of deep exhaled breath to mouth air is significantly higher in type 1 DM than type 2 DM patients. The concentration of VSC shows no significant difference. Though more cases should be studied, there is a possibility that the acetone ratio might reflect metabolic disorder of type 1 DM patients.

The oral treponemes were isolated on nine media and classified according to Anaerobe Laboratory Manual (1977) . The four media, which were used with the plate-in-bottle method, were Medium 10 (M10), M10 supplemented with 10% rumen fluid, M10 supplemented with 10% rabbit serum and cocarboxylate, and M10 added with rifampicin. The five media with the anaerobic glove box method were New Oral Spirochetes (NOS) medium, NOS medium added with rifampicin, alternated modified Oral Treponemes Isolation (aOTI) medium, and alternat-ed M10 for anaerobic glove box. The isolation rate of the oral treponemes from 59 subgingival plaque samples of various forms of periodontal diseases was 85 percent. Ninety clinical isolates were subcultured and classified into six groups (I-VI) based on the carbohydrate fermentation and metabolic end products. Three saccaharolytic groups were further divided into nine subgroups by the fermentation patterns of sucrose, lactose, maltose and rhamnose. Two saccaharolytic subgroups were identified as Treponema socranskii, and two asaccharolytic groups were identified as “T. denticola” and “T. vincentii”. However, the other subgroups and group could not be identified according to the characteristics of the presently recognized species.

Oral health examinations were held in summer continuously for 2 years with general health checks in a rural town. We included oral health check, practice of oral cleaning, and measurement of oral malodor in the examination. Aim of this study was to examine the difference of impression in the oral health examination between younger and older participants by questionnaires. No difference was found between male and female ratio in each generation. Also, no difference was seen as for ratio of joiners of oral cleaning and ratio of their satisfaction after the practice. Significant difference between two generations was seen as for strong satisfaction ratio with explanation about the result of oral malodor, and effective motivation ratio for oral hygiene caused by measurement of oral malodor. The oral health examination held with general checks with measurement of oral malodor seemed more impressive to older generation.

Although the mechanism provoking Sjoren’s syndrome has been extensively studied, the pathogenesis remains obscure. We examined immunohistochemically the expression of CD134 ligand, CD137 ligand, glucocorticoid-induced TNF receptor ligand, and B cell-activating factor of the tumor necrosis factor family in autoimmune saialadenitis of submandibular glands of MRL/lpr mice compared with those of MRL/+ control mice to elucidate the pathogenesis of Sjogren’s syndrome. These four molecules are costimulatory factors usually expressed in antigen presenting cells. Unexpectedly, we find that ductal epithelial cells of MRL/lpr mice strongly express the four costimulatory factors, whereas those of MRL/+ control mice show negative or very weak expression.

We have already reported the hardness of the gingiva in young human subjects measured by a tonometer. In this study, the age-related changes in the hardness of the human gingival tissue were examined. The measurement was made on the young and the elder people who had clinically healthy gingival tissue using a tonometer. The labial surfaces of attached gingival site were selected as examination sites. The gingiva was significantly harder with elder subjects than the young subjects. The results indicated the age-related changes of gingival hardness.

The aim of this study is to measure the acoustic characteristics of human extracted teeth with sound or dentine caries lesion by using an ultrasonic device and to compare the readouts to the diagnosis based on the DIAGNOdent (KaVo institution, Germany) and dyed with Caries-Check (Nishika institution, Tokyo).

Swallowing, which is important for eating and drinking for survival, is one of the basic functions of the mouth. The purpose of this study was to develop a safe and easily-handleable measuring device to evaluate swallowing processes in younger generations. An intra-oral pressure-measuring device estimated the intra-oral positive and negative pressures produced by sucking or blowing. The results indicated that the maximal positive pressure or minimal negative pressure increased or decreased depending upon age. This suggests that the function to produce intra-oral negative pressure, which was made with lip and faucial isthmus closure for sucking, and positive pressure, which was made with lip closure for blowing, was developed with age or physical strength. This simple measuring system of oral pressure was useful in fieldworks for screening oral dysfunction among all generations, not depending upon the condition of tooth or dentition.

The purpose of this study is to clarify the spread conditions of the school-based fluoride mouth rinsing (s-FMR) program since 1983 and to estimate the total number of schools and children who would be participating in the s-FMR for proposition regarding final assessment of Healthy Japan 21 in 2010, and to calculate the estimated number in 2020. In 2008, the total number of schools and children who participated in the program were 6,433 and 674,141, respectively. It shows that the number of children participating in the program corresponds to 5.1% of the same-aged population. The estimated number of schools and children participating in the program would approximately be 7,262 and 7,386,231 in 2010, and 14,770, and 1,523,632 in 2020, respectively, calculated on basis of data from 1983 to 2008. We need the cooperation of dental organizations, dental schools, and municipal corporations to achieve the goals in the s-FMR.

“8020” Movement (retain 20 natural teeth at the age of 80) has proposed from 1989 for prolonging the life span of teeth. The purpose of this study is to predict the attainment time “8020”. We analyze the data of the nine national surveys of dental diseases in Japan conducted every 6 years from 1957 through 2005 to determine the actual trend of retention of natural teeth. The average numbers of remaining teeth of ten 6-year stratified age groups are determined by calculating the rates of tooth loss in 6 years of corresponding age groups for the period 1957 through 2005. Future rates of tooth loss are then estimated using regression analysis on the assumption that the present rate of improvements in dental care, preventive measures, and public awareness for oral health would continue. Our estimation suggests that the “8020” goal would not be attained until after 2029 or 2035.

In the present study, we examined the applicability of tonometer to evaluate the hardness of human gingival tissue. For this purpose, induction-based impact method for measuring intraocular pressure was applied. The measurement was made on the young male subjects (n = 7, aver. 24.8 years) who had clinically healthy gingival tissue. The labial surfaces of attached gingival site between teeth were selected as examination. The gingival pressure ranged between 18 and 77 (n = 70, mean ± SD; 44.4 ± 8.1 mmHg). The results indicated that tonometric measurement of the gingival tissue could give quantitative information of the gingival inflammation.

To diagnose the activities and progressions of dental caries lesions, we developed nondestructive measuring device to detect and quantify the mineral loss in the early stage of caries. This novel device with ultrasonic technology measures acoustic frequency characteristics of the tooth surface. Extracted human tooth were embedded in polymethylmethacrylate and polished. The results of the repeated measurements indicated the sufficient reproducibility of acoustic measurements in same samples. Since this acoustic measurement was influenced by the moist condition of tooth surfaces, tooth surfaces should be air-dried and quickly measured for the reproducibility in clinics. We developed the nondestructive ultrasonic measuring device to detect the mineral loss from tooth surfaces and diagnose the initial change of progression of dental caries lesions in enamel and dentine.

Halitosis is a common oral concern and patients often seek help from dentists. The purpose of this study is to evaluate psychological characteristics of halitosis patients and their changes with treatment. The subjects consisted of 150 halitosis patients and 64 non-halitosis patients. They were requested to complete Egogram and the halitosis scale questionnaires, before and after treatment. The results indicated that halitosis patients improved in the objective recognition of their malodor level, their obsession with halitosis, and interpersonal communication after treatment. Therefore, the ideal dentist attitude for halitosis treatment is to help patients overcome their obsession by examining their breath level repeatedly and encourage them to develop social skills. However, these subjects had a tendency for social phobia, and its removal was not easy. Therefore, it would be essential that dentists continue to accept their complaints and relapse of their obsession with bad breath sincerely.

We carried out residents-attractive dental health examinations by increasing the learning contents with systemic health examination of a rural town in Japan. Town staffs or some residents who had finished training programs participated in the dental examinations as staffs. Oral malodor was measured to motivate oral hygiene of examinees. We prepared questionnaires and asked the impression of examinees about “the dental examination with learning” 7 months after the examination. Questionnaires showed that 85% of dental examinees recognized it as satisfactory. This fact indicates the possibility that the new dental examination can be a model for oral health promotion in the community.

We investigated the effects of Glycosaminoglycans (GAGs) on mouse monocytic cell line in regard to their differentiation, proliferation, and function in vitro. RAW 264.7 cells were cultured with receptor activator of NF-kappaB ligand (RANKL) and various GAGs. Osteoclastic cells were visualized by staining for tartrate-resistant acid phosphatase (TRAP) and detected using a phenyl-phosphate substrate method. RAW 264.7 cells were also cultured with stimulants contained in BD BioCoat OSTEOLOGIC(TM) kit, and bone resorption activity was assessed by counting the numbers of resorption pits. We also examined the effect of heparin on cell growth using MTT assay, while the expression level of c-Src protein was determined by immunoblot analysis. Heparin suppressed TRAP-positive multinucleated cell formation and TRAP activity induced by RANKL, whereas the other GAGs showed no effects on osteoclast differentiation. Heparin also inhibited the formation of resorption pits, while the others did not. In the MTT assay, none of the tested GAGs had an influence on RAW 264.7 cell proliferation. However, heparin reduced the level of c-Src protein in RAW 264.7 cells stimulated with RANKL. To determine the affinity of heparin and RANKL, they were subjected by HiTrap heparin column chromatography and each fraction was collected. Western blotting analysis revealed the expression of RANKL in the fraction bound to heparin. The binding of RANKL and heparin was confirmed by quartz-crystal microbalance. These results indicate that the inhibitory effect of heparin toward osteoclastogenesis induced by RANKL is due to the binding of heparin to RANKL.

Candida albicans is both a commensal and a pathogen in the oral mucosa. Previous studies have indicated that epithelial cell-associated carbohydrate moiety can inhibit C. albicans growth. In the present study, the mechanisms by which epithelial cells inhibit Candida growth were studied by examining the effect of hyaluronan (HA). A coculture of C. albicans and KB cells or COS-7 cells inhibited in vitro growth of the fungus by 50-87% at an effector-to-target (E:T) ratio of 80:1. Removing extracellular HA by hyaluronidase caused a significant decrease in the anti-Candida activity of the cells. In addition anti-Candida activity was observed at 1 micro g/ml HA (2000 kDa). The antifungal activity of extracellular HA was further studied by transiently transfecting COS-7 cells with human HSA1, HSA2, or HSA3 in order to produce high levels of extracellular HA. All of the transfectants inhibited C. albicans growth in vitro by 51-65% compared to 38% inhibition by the vector control (P

The aims of this study were to identify hydrogen sulfide (H2S)-producing bacteria among tongue biofilm microflora and to investigate the relationship between bacterial flora and H2S levels in mouth air. Oral malodour levels in 10 subjects (age 21–56 years) were assessed by gas chromatography, and Breathtron and organoleptic scores. Based on these assessments, subjects were divided into two groups: an odour group and a no/low odour group. Tongue coatings were sampled and spread onto Fastidious Anaerobe Agar plates containing 0.05 % cysteine, 0.12 % glutathione and 0.02 % lead acetate, and were then incubated anaerobically at 37 °C for 2 weeks. Bacteria forming black or grey colonies were selected as H2S-producing phenotypes. The numbers of total bacteria (P < 0.005) and H2S-producing bacteria (P < 0.05) in the odour group were significantly larger than those in the no/low odour group. Bacteria forming black or grey colonies (126 isolates from the odour group; 242 isolates from the no/low odour group) were subcultured, confirmed as producing H2S and identified according to 16S rRNA gene sequencing. Species of Veillonella (38.1 % in odour group; 46.3 % in no/low odour group), Actinomyces (25.4 %; 17.7 %) and Prevotella (10.3 %; 7.8 %) were the predominant H2S-producing bacteria in both the odour and no/low odour groups. These results suggest that an increase in the number of H2S-producing bacteria in the tongue biofilm is responsible for oral malodour, although the bacterial composition of tongue biofilm was similar between the two groups.

Hyaluronic acid (HA) is a component of the extracellular matrix that has been shown to play an important role in bone formation, resorption, and mineralization both in vivo and in vitro. We examined the effects of HA at several molecular weights on osteoclast formation and function induced by RANKL (receptor activator of NF-kappa B ligand) in a mouse monocyte cell line (RAW 264.7). HA at M(r)8,000 (low molecular weight HA (LMW-HA)) enhanced tartrate-resistant acid phosphatase-positive multinucleated cell formation and tartrate-resistant acid phosphatase activity induced by RANKL in a dose-dependent manner, whereas HA at M(r)900,000 (high molecular weight HA (HMW-HA)) showed no effect on osteoclast differentiation. LMW-HA enhanced pit formation induced by RAW 264.7 cells, whereas HMW-HA did not, and LMW-HA stimulated the expression of RANK (receptor activator of NF-kappa B) protein in RAW 264.7 cells. In addition, we found that LMW-HA enhanced the levels of c-Src protein and phosphorylation of ERKs and p38 MAPK in RAW 264.7 cells stimulated with RANKL, whereas the p38 MAPK inhibitor SB203580 inhibited RANKL-induced osteoclast differentiation. This enhancement of c-Src and RANK proteins induced by LMW-HA was inhibited by CD44 function-blocking monoclonal antibody. These results indicate that LMW-HA plays an important role in osteoclast differentiation and function through the interaction of RANKL and RANK.

Ketone bodies including acetone are disease biomarkers for diabetes that sometimes causes severe ketoacidosis. The present study was undertaken to clarify the significance of exhaled acetone and plasma ketone bodies at bedside in a clinical setting. The oral glucose tolerance test (OGTT) was performed in 10 healthy Japanese volunteers (five females and five males). Exhaled breath acetone and volatile sulfide compounds (VSCs) in mouth air were measured simultaneously with blood sampling during the OGTT using a portable gas chromatograph equipped with an In2O3 thick-film type gas sensor and a VSC monitor. Acetone, β-hydroxybutyrate (β-OHB) and acetoacetate (AcAc) in blood plasma as well as glucose and insulin were examined. Oral conditions were examined based on the Community Periodontal Index (CPI) by one dentist. In addition, the same type of analysis was applied to two uncontrolled type 2 diabetes mellitus patients hospitalized at Tohoku University Hospital. Exhaled acetone was measured at the same time as blood withdrawal in the morning before breakfast and at night before bed at the beginning, the middle, and the end of hospitalization. All volunteers showed normal OGTT patterns with no ketonuria and periodontitis; however, there were significant correlations between breath acetone and plasma β-ΟΗΒ and between breath acetone and plasma AcAc under fasting conditions. Breath acetone of the type 2 diabetes mellitus patients showed positive correlations with plasma glucose when the level of plasma glucose tended to decrease during hospitalization. In spite of a very limited number of cases, our results support the idea that exhaled breath acetone may be related to plasma β-OHB and AcAc, which reflect glucose metabolism in the body.