||Haruhiko Kashiwazaki, Takae Matsushita, Junichi Sugita, Akio Shigematsu, Kumiko Kasashi, Yutaka Yamazaki, Takashi Kanehira, Takeshi Kondo, Tomoyuki Endo, Junji Tanaka, Satoshi Hashino, Mitsufumi Nishio, Masahiro Imamura, Yoshimasa Kitagawa, Nobuo Inoue, A comparison of oral mucositis in allogeneic hematopoietic stem cell transplantation between conventional and reduced-intensity regimens, Supportive Care in Cancer, 10.1007/s00520-011-1164-2, 20, 5, 933-939, 2012.05, Severe oral mucositis developed in allogeneic hematopoietic stem cell transplantation (HSCT) accompanies intolerable pain and risk for systemic bacteremia infection. Conventional stem cell transplantation (CST) and reduced-intensity regimens for allogeneic HSCT (RIST) may differently affect the occurrence and severity of oral mucositis. Here, we comparatively examined oral mucositis in patients undergoing CST and that in RIST patients to search for measures to alleviate oral mucositis. We retrospectively analyzed the data of 130 consecutive patients undergoing HSCT (conventional, 60; RIST, 70). Oral mucositis was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. We also investigated the risk factors for severe oral mucositis in each regimen. The incidence of oral mucositis was not significantly different between RIST and CST patients. The use of opioid analgesics to control pain due to oral mucositis was significantly less in patients undergoing RIST compared with those receiving CST. The risk factors for severe oral mucositis, determined by univariate and multivariate analyses, were "younger age (<40)" in CST and "longer duration of neutropenia (≥14 days)" in RIST. Although the incidences of oral mucositis were almost the same, the need for opioid analgesics and the risk factors for severe oral mucositis differed between CST and RIST patients..
||Eriko Harada, Shingo Moriya, Ayumi Murata, Masumi Muramatsu, Haruhiko Kashiwazaki, Kunihiko Kobayashi, Kenji Notani, Nobuo Inoue, Relationship between subjective assessment of oral health and medical expenses in community-dwelling elderly persons, Gerodontology, 10.1111/j.1741-2358.2011.00459.x, 29, 2, e246-e252, 2012.06, Objectives: The increasing medical expenses of elderly persons in Japan's rapidly ageing society have become a major concern. It is therefore important to elucidate the factors associated with such escalation. Here, we focused on the relationship between subjective self-assessment of oral health, as an index of general health, and medical expenses (excluding dental repair) under the hypothesis that oral health contributes to general medical expenses. Several studies have shown that oral health status is correlated with general health status among elderly persons. We speculated that oral health status might show a relation with medical costs among elderly persons. However, few studies have investigated this relationship to date. Materials and Methods: Participants were 259 elderly subjects (range: 65-84 years; 120 men, 139 women) residing independently. Subjective assessment of oral health was evaluated by their responses ('Good', 'Not good' and 'Not at all good') on a survey questionnaire. The correlation between subjective assessment of oral health and medical expenditure was analysed using Spearman's rank method, the Mann-Whitney U-test and the Kruskal-Wallis test. Medical expenses were used as the dependent variable in multinomial logistic regression analysis with background and intraoral factors as independent variables. Results: A slight yet statistically significant correlation was observed between subjective assessment of oral health and outpatient treatment fees. Conclusion: The findings revealed that subjective assessment of oral health is significantly and independently related to the medical expenses of community-dwelling elderly persons after adjusting for social background, living environment and physical factors..
||Michiko Terada, Kenji Izumi, Hisashi Ohnuki, Taro Saito, Hiroko Kato, Marie Yamamoto, Yoshiro Kawano, Kayoko Nozawa-Inoue, Haruhiko Kashiwazaki, Toshiyuki Ikoma, Junzo Tanaka, Takeyasu Maeda, Construction and characterization of a tissue-engineered oral mucosa equivalent based on a chitosan-fish scale collagen composite, Journal of Biomedical Materials Research - Part B Applied Biomaterials, 10.1002/jbm.b.32746, 100 B, 7, 1792-1802, 2012.10, This study was designed to (1) assess the in vitro biocompatibility of a chitosan-collagen composite scaffold (C3) constructed by blending commercial chitosan and tilapia scale collagen with oral mucosa keratinocytes, (2) histologically and immunohistochemically characterize an ex vivo-produced oral mucosa equivalent constructed using the C3 (EVPOME-C), and (3) compare EVPOME-C with oral mucosa constructs utilizing AlloDerm® (EVPOME-A), BioMend® Extend™ (EVPOME-B), and native oral mucosa. C3 scaffold had a well-developed fibril network and a sufficiently small porosity to prevent keratinocytes from growing inside the scaffold after cell-seeding. The EVPOME oral mucosa constructs were fabricated in a chemically defined culture system. After culture at an air-liquid interface, EVPOME-C and EVPOME-B had multilayered epithelium with keratinization, while EVPOME-A had a more organized stratified epithelium. Ki-67 and p63 immunolabeled cells in the basal layer of all EVPOMEs suggested a regenerative ability. Compared with native oral mucosa, the keratin 15 and 10/13 expression patterns in all EVPOMEs showed a less-organized differentiation pattern. In contrast to the β1-integrin and laminin distribution in EVPOME-A and native oral mucosa, the subcellular deposition in EVPOME-C and EVPOME-B indicated that complete basement membrane formation failed. These findings demonstrated that C3 has a potential application for epithelial tissue engineering and provides a new potential therapeutic device for oral mucosa regenerative medicine. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012..
||Toshiyuki Akazawa, Masaru Murata, Jun Hino, Futami Nagano, Tatsuhiro Shigyo, Takafumi Nomura, Hiroyuki Inano, Kohji Itabashi, Tohru Yamagishi, Katsuo Nakamura, Touru Takahashi, Shunji Iida, Haruhiko Kashiwazaki, Surface structure and biocompatibility of demineralized dentin matrix granules soaked in a simulated body fluid, Applied Surface Science, 10.1016/j.apsusc.2012.01.053, 262, 51-55, 2012.12, Demineralized dentin matrix (DDM) granules with excellent biocompatibility were easily prepared using unnecessary human teeth by a new cooling-pulverizing and demineralizing technique. Extracted human teeth were pulverized together with saline ice at 12,000 rpm-rotation number of a ZrO 2 blade for 30 s in a ZrO 2 vessel. The pulverized granules exhibited the particle size distribution of 0.5-2 mm that was efficient for regeneration of alveolar bone. The (Ca/P) ratios of the granules were 1.60-1.66, which were close to the stoichiometric value of 1.67 for standard hydroxyapatite (HAp). Small amounts of Na + and Mg 2+ ions present at less than 1% were detected. The pulverized granules were dissolved with stirring under 500 rpm for 10-60 min in 2.0%-HNO 3 solutions to obtain partial or complete DDM granules. As the dissolution time increased, crystallinity of HAp phase lowered and asperity on surfaces of the granules became outstanding due to elution of mineral components. At the dissolution of 60 min, the pulverizing granules were completely demineralized and the weight decreased to about one-fifth. To improve surface activity of the DDM granules without denaturation of bone growth factors, the DDM granules were soaked at 309.5 K and pH 7.40 in a simulated body fluid (SBF). HAp microcrystals were gradually precipitated on surfaces of the DDM granules with increasing the soaking time. Different morphology of the precipitates was observed, depending on the demineralization situation of the pulverized granules. For the DDM with low dissolution efficiency of 42%, porous bone-like apatites at 24 h after the soaking and fiber-oriented aggregates at 144 h were recognized. The bioactive DDM granules were implanted into the subcutaneous tissues of the back region of rats. At 4 weeks after the implantation, bio-absorption by comparatively small amounts of multi-giant cells was recognized around the surface layers of DDM granules..
||Haruhiko Kashiwazaki, Naoki Harada, Toshiyuki Akazawa, Md Arafat Kabir, Yasuhito Minamida, Masaru Murata, Bone augmentation using novel unidirectional porous hydroxyapatite with bone morphogenetic protein-2 on rat skull, Journal of Hard Tissue Biology, 10.2485/jhtb.22.337, 22, 3, 337-342, 2013.07, Unidirectional porous hydroxyapatite (UDPHAp) is a material whose microstructure consists of cross- sectional oval pores with a pore diameter in the range of 100-300 m that penetrate through the material. UDPHAp has proven suitable for osteogenesis and angiogenesis. The present study was designed to evaluate the osteogenic effect of a newly developed UDPHAp as a carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat onlay graft model. UDPHAp was implanted beneath the calvarial periosteum of rats to simulate alveolar bone augmentation in a clinical condition. At 2 weeks after implantation, UDPHAp with rhBMP-2 resulted in active bone formation, and the augmented bone was connected directly with the original bone, whereas commercialized porous hydroxyapatite (PHAp) with rhBMP-2 showed little bone formation. These results suggest that UDPHAp in this model is suitable for onlay graft and is an effective biomaterial for the rhBMP-2 delivery system..
||Naoki Kakudate, Tsukasa Muramatsu, Mami Endoh, Kazuhito Satomura, Takeyoshi Koseki, Yuji Sato, Kayoko Ito, Tadashi Ogasawara, Seiji Nakamura, Etsuo Kishimoto, Haruhiko Kashiwazaki, Yoshihisa Yamashita, Kimio Uchiyama, Tatsuji Nishihara, Yutaka Kiyohara, Yasuaki Kakinoki, Factors associated with dry mouth in dependent Japanese elderly, Gerodontology, 10.1111/j.1741-2358.2012.00685.x, 31, 1, 11-18, 2014.03, 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..
||Aya Yokoi, Takayuki Maruyama, Reiko Yamanaka, Daisuke Ekuni, Takaaki Tomofuji, Haruhiko Kashiwazaki, Yutaka Yamazaki, Manabu Morita, Relationship between acetaldehyde concentration in mouth air and tongue coating volume, Journal of Applied Oral Science, 10.1590/1678-775720140223, 23, 1, 64-70, 2015.01, Objective: Acetaldehyde is the first metabolite of ethanol and is produced in the epithelium by mucosal ALDH, while higher levels are derived from microbial oxidation of ethanol by oral microflora such as Candida species. However, it is uncertain whether acetaldehyde concentration in human breath is related to oral condition or local production of acetaldehyde by oral microflora. The aim of this pilot study was to investigate the relationship between physiological acetaldehyde concentration and oral condition in healthy volunteers. Material and Methods: Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years old) participated in the present study. Acetaldehyde concentration in mouth air was measured using a portable monitor. Oral examination, detection of oral Candida species and assessment of alcohol sensitivity were performed. Results: Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5, 306.3) ppb. Acetaldehyde concentration in participants with a tongue coating status score of 3 was significantly higher than in those with a score of 1 (p<0.017). After removing tongue coating, acetaldehyde concentration decreased significantly (p<0.05). Acetaldehyde concentration was not correlated with other clinical parameters, presence of Candida species, smoking status or alcohol sensitivity. Conclusion: Physiological acetaldehyde concentration in mouth air was associated with tongue coating volume..
||Toshihiro Matsukawa, Daigo Hashimoto, Junichi Sugita, Seitarou Nakazawa, Takae Matsushita, Haruhiko Kashiwazaki, Hideki Goto, Masahiro Onozawa, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Yutaka Yamazaki, Takanori Teshima, Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD, International journal of hematology, 10.1007/s12185-016-1996-0, 104, 1, 117-124, 2016.07, Allogeneic hematopoietic stem cell transplantation is a curable treatment for hematological diseases. Graft-versus-host disease (GVHD) causes morbidity and mortality after HSCT. Methotrexate (MTX) is used for GVHD prophylaxis, but its appropriate dose remains unclear. In the present study, we compared the efficacy and toxicity of 15-10-10 MTX (day +1: 15 mg/m2; days +3 and +6: 10 mg/m2) with 10-7-7 MTX (day +1: 10 mg/m2; day +3 and +6: 7 mg/m2) in combination with tacrolimus. The cumulative incidence rates of grades II–IV acute GVHD, grades III–IV acute GVHD and chronic GVHD in the 15-10-10 MTX and 10-7-7 MTX groups did not differ to a statistically significant extent. The median time for neutrophil engraftment in the 15-10-10 MTX group was 16 days (range, 11–31 days), while that in the 10-7-7 group was 15 days (range, 12–19 days) (P = 0.024). Moreover, the median time for platelet recovery was significantly shorter in the 10-7-7 MTX group (22 days; range, 13–49 days) than that in the 15-10-10 MTX group (27 days; range, 9–405 days) (P = 0.027). The duration of oral mucositis was significantly shorter in the patients who received a reduced dose of MTX (median, 4.5 vs 13.0 days; P = 0.013). In conclusion, GVHD prophylaxis with a reduced dose of MTX was associated with earlier engraftment and earlier recovery from mucositis in comparison to a standard dose of MTX, without affecting the incidence of GVHD..
||Seitaro Nakazawa, Ken Ichiro Sakata, Shanshan Liang, Kazuhito Yoshikawa, Hisashi Iizasa, Mitsuhiro Tada, Jun Ichi Hamada, Haruhiko Kashiwazaki, Yoshimasa Kitagawa, Yutaka Yamazaki, Dominant-negative p53 mutant R248Q increases the motile and invasive activities of oral squamous cell carcinoma cells, Biomedical research (Tokyo, Japan), 10.2220/biomedres.40.37, 40, 1, 37-49, 2019.01, The tumor suppressor gene TP53 (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. TP53 is well known to be the most frequent target of genetic mutations in nearly half of human cancers including oral squamous cell carcinoma (OSCC). Many p53 mutants including R248Q and R248W not only lose its tumor-suppressor activities, but also interfere with the functions of wild-type p53; this is so-called dominant-negative (DN) mutation. The DN p53 mutation is a predictor of poor outcome in patients with various cancers, and also a risk factor for metastatic recurrence in patients with OSCC. Recently it has been reported that DN p53 mutants acquire new oncogenic activities, which is named gain-of-function (GOF). This study aimed at determining whether R248Q and R248W were involved in OSCC cells' acquiring aggressive phenotypes, using SAS, HSC4 and Ca9-22 cell lines. First, two mutants p53, R248Q and R248W, were respectively transfected into SAS cells harboring recessive-type p53 (E336X). As a result, SAS cells expressing R248Q showed highly spreading, motile and invasive activities compared to parent or mock-transfected cells whereas those expressing R248W did not increase those activities. Secondly, in HSC4 cells harboring R248Q and Ca9-22 cells harboring R248W, expressions of the mutants p53 were inhibited by the transfection with siRNAs targeting p53. The inhibition of the mutants p53 decreased spreading, motile and invasive activities of HSC4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, induces more motile and invasive potentials in human OSCC cells..
||Kiyomi Iyota, Shinsuke Mizutani, Saori Oku, Misa Asao, Toshiko Futatsuki, Ryosuke Inoue, Yuko Imai, Haruhiko Kashiwazaki, A cross-sectional study of age-related changes in oral function in healthy Japanese individuals, International journal of environmental research and public health, 10.3390/ijerph17041376, 17, 4, 2020.02, Background: Oral function deterioration is related to a variety of factors, including aging, decline in activities of daily living, malnutrition, and cognitive decline. This cross-sectional study examined the effects of aging on oral function in healthy individuals. Methods: A retrospective study was conducted on 175 healthy, independent patients aged 40–89 years, without dementia and with ≥20 teeth, who visited a local dental clinic in Japan. Patients were compared with 92 university students aged 20–29 years. The seven criteria proposed by the Japanese Society of Gerodontology to diagnose “oral hypofunction” were observed and statistically analyzed. Results: Compared with those in the control group, the degree of tongue coating was increased in the group aged over 80 years, occlusal force was decreased in the group aged 70–79 years, tongue motor function was decreased in the groups aged 60–69 years and older, and tongue pressure was decreased in the groups aged 70–79 years and older. Conclusions: Healthy, independent individuals maintained several oral function criteria across aging, including oral mucosal wetness, occlusal force, lip motor function, masticatory function, and swallowing function. Tongue motor function and tongue pressure decreased with aging, indicating that these may be rehabilitation targets..