Updated on 2024/10/25

Information

 

写真a

 
KASHIWAZAKI HARUHIKO
 
Organization
Faculty of Dental Science Department of Dental Science Professor
School of Dentistry Department of Dentistry(Concurrent)
Graduate School of Dental Science (Concurrent)
Graduate School of Dental Science Department of Dental Science(Concurrent)
Title
Professor
Contact information
メールアドレス
Tel
0926426484
External link

Degree

  • PhD

Research History

  • Hokkaido University   

Research Interests・Research Keywords

  • Research theme: Development of Oral Function Improvement Program for Prevention of Frailty Using IoT

    Keyword: Oral Function, Prevention of Frailty

    Research period: 2020.8 - 2022.8

  • Research theme: Studies on relationship between oral and general health

    Keyword: oral health, general health, elderly, oral care, geriatric medicine

    Research period: 2018.6

Papers

  • Oral management for a patient with trismus accompanied by Isaacs' syndrome: a case report

    Tani, A; Mizutani, S; Watanabe, M; Irie, T; Masaki, K; Isobe, N; Kashiwazaki, H

    BMC ORAL HEALTH   24 ( 1 )   716   2024.6   ISSN:1472-6831

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    Language:English   Publisher:BMC Oral Health  

    Background: Isaacs’ syndrome, also known as neuromyotonia or peripheral nerve hyperexcitability, is a rare disorder that affects the peripheral nervous system. Clinical findings include cramps, fasciculations, and myokymia; however, there are few reports of dental treatment for trismus. Case presentation: A patient with trismus due to Isaacs’ syndrome experienced swelling and pain in the gingiva surrounding his right lower first molar. He was diagnosed with chronic apical periodontitis by a dentist near his home. However, the patient was informed that dental treatment and medication could not be administered because of the presence of Isaacs’ syndrome, and he visited the Geriatric Dentistry and Perioperative Oral Care Center at Kyushu University Hospital 2 weeks later. The patient’s painless mouth-opening distance (between incisors) was 20 mm at that time, and medication, including amoxicillin capsules and acetaminophen, was administered because the dental extraction forceps or endodontic instruments were difficult to insert into the oral cavity for treatment. Two months after his initial visit, the patient visited us complaining of pain in the same area. However, he had recently undergone plasmapheresis treatment in neurology to alleviate limited mouth opening and systemic myalgia, resulting in a pain-free mouth-opening distance of approximately 35 mm. During this temporary period in which he had no restriction in mouth opening, we performed tooth extraction and bridge restoration on the mandibular right first molar and created an oral appliance for sleep bruxism. Conclusions: Plasmapheresis therapy transiently reduced trismus, rendering dental interventions feasible, albeit temporarily. This case report underscores the importance of close collaboration between neurologists and dentists who encounter similar cases while furnishing valuable insights to inform dental treatment planning.

    DOI: 10.1186/s12903-024-04485-2

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  • A mixture of extracts from natural ingredients reduces the neurotoxic polarization of microglia via modulating NF-κB/NF-E2-related factor 2 activation

    Gui, SG; Ni, JJ; Mizutani, S; Shigematsu, N; Nakanishi, H; Kashiwazaki, H; Wu, Z

    FOOD SCIENCE & NUTRITION   12 ( 5 )   3745 - 3758   2024.5   ISSN:2048-7177

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    Neurotoxic microglia-provoked neuroinflammation is implicated in cognitive decline in Alzheimer's disease (AD). Supplementation with Ginkgo biloba, phosphatidylserine, Curcuma longa, and propolis is reported to improve the cognitive functions of elderly people; however, the underlying mechanisms of this combination of natural ingredients are unknown. We investigated the effects of a mixture of extracts from propolis, Coffea arabica, Gotu kola, phosphatidylserine, Ginkgo biloba, and Curcuma longa (mixture) on microglia polarization after exposure to amyloid β1-42 (Aβ1-42, 1 μM) and lipopolysaccharide from Porphyromonas gingivalis (PgLPS, 1 μg/mL), using MG6 and BV2 microglial cells. Exposure to Aβ1-42 and PgLPS (AL) raised the mRNA expression of IL-1β, TNF-α, and IL-6, nuclear translocation of p65 NF-κB in MG6 cells and BV2 cells, and mitochondrial reactive oxygen species (ROS) production in MG6 cells. The mixture dramatically suppressed the mRNA expression of IL-1β, TNF-α, and IL-6, but significantly promoted that of IL-10, TGFβ1, and BDNF in AL-exposed MG6 and BV2 cells. Furthermore, the mixture significantly suppressed the nuclear translocation of p65 NF-κB but significantly promoted that of NF-E2-related factor 2 (Nrf2) in AL-exposed MG6 and BV2 cells. Furthermore, the mixture significantly ameliorated mitochondrial ROS production but increased mitochondrial membrane potential in MG6 cells. These observations strongly suggest that the mixture demotes the neuropathic polarization of microglia by modulating NF-κB/Nrf2 activation and improving mitochondrial functions. This study supplies the potential mechanisms of the efficacy of a combination of natural ingredients that can be applied in the prevention of cognitive decline in AD and aging by targeting microglia-mediated neuroinflammation.

    DOI: 10.1002/fsn3.4045

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  • A Case of Rehabilitation for an Older Patient with Eating and Swallowing Dysfunction Due to Parkinsonism

    Oike Asami, Yamazoe Junichi, Kashiwazaki Haruhiko

    Ronen Shika Igaku   38 ( supplement )   64 - 68   2024.1   ISSN:09143866 eISSN:18847323

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    Language:Japanese   Publisher:Japanese Society of Gerodontology  

    <p> 緒言:水頭症に対するシャント術後の中脳下垂によって生じたパーキンソニズムによる摂食嚥下障害の高齢者に対して,経口摂取再開を目的とした摂食嚥下リハビリテーションを行った症例を報告する。</p><p> 症例:65歳,女性。X年4月頃から固形物の飲み込みにくさを自覚した。その後,水分摂取も困難となり,6月に当院脳神経内科に入院となった。パーキンソニズムおよび嚥下失行と診断され,入院8日後に摂食嚥下リハビリテーションならびに口腔健康管理の依頼を受け,当科初診となった。初診時の口腔機能精密検査の結果,咀嚼能力の極度な低下を認めた。</p><p> 経過:入院12日後よりゼリーを用いた直接訓練を開始し,入院28日後には昼のみ嚥下調整食3(日本摂食嚥下リハビリテーション学会嚥下調整食分類2021に準ずる)を開始することができた。しかしその2日後にL-dopaの副作用による不随意運動が悪化し,再度ゼリーを用いた直接訓練に変更した。入院40日後には再度昼のみ嚥下調整食3を開始することができた。入院60日後に転院となるまで直接訓練を継続し,最終的に3食とも嚥下調整食4を摂取できるようになった。転院前に行った口腔機能精密検査では咀嚼能力の大幅な上昇を認めた。</p><p> 考察:本症例では,悪化傾向のパーキンソニズムを呈する患者でありながら,可及的早期に,かつ継続的に患者の口腔機能の変化に寄り添った医療を提供することで,摂食状況の改善に貢献することができた。</p>

    DOI: 10.11259/jsg.38.supplement_64

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  • A Case of Improvement of Mastication Ability in a Patient with Osteoporosis Taking Bisphosphonate for a Long Time by Treatment Overdenture

    Inoue Subaru, Yamazoe Junichi, Kashiwazaki Haruhiko

    Ronen Shika Igaku   38 ( supplement )   69 - 73   2024.1   ISSN:09143866 eISSN:18847323

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    Language:Japanese   Publisher:Japanese Society of Gerodontology  

    <p> 緒言:ビスフォスフォネート(BP)製剤の長期服用は顎骨壊死リスクがあり,抜歯後合併症のハイリスク要因となるが,咀嚼の妨げになる不良な歯の残存は口腔機能低下,低栄養の要因となる。今回,BP製剤長期服用の骨粗鬆症患者に対し,残根上義歯作製により咀嚼能力が改善し,食品摂取状況の改善がみられた症例を経験したので報告する。</p><p> 症例:87歳,女性。上顎臼歯部の動揺による食事摂取困難を主訴に歯科受診。既往歴に骨粗鬆症があり,BP製剤を長期服用。口腔衛生状態不良であり,残根歯,動揺歯を多数認めた。</p><p> 経過:初診時,咀嚼能力を「内田らの摂食状況調査表」にて評価したところ,食品摂取可能率は45%であった。口腔機能検査では5項目で口腔機能低下症を認めた。抜歯適応歯を認めたが,全身状態や栄養状態,早期摂食改善の希望を考慮し抜歯は行わず,上下顎残根上義歯を作製し,咀嚼能力改善を図ることとした。義歯装着から約1カ月後には,食品摂取可能率は60%に増加し,口腔機能検査でも数値改善が認められた。</p><p> 考察:今回,残根上義歯作製により咀嚼能力が改善したことで,経口摂取可能な食事のバリエーションが増加し,効率的な栄養摂取が可能となったと考える。また,患者の主訴を改善することができたことで,食事に対するモチベーション向上にも寄与できたと考える。</p>

    DOI: 10.11259/jsg.38.supplement_69

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  • Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning

    Oku, S; Futatsuki, T; Imamura, Y; Hikita, H; Inada, A; Mizutani, S; Mori, Y; Kashiwazaki, H

    SUPPORTIVE CARE IN CANCER   31 ( 9 )   521   2023.9   ISSN:0941-4355 eISSN:1433-7339

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    Purpose: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. Methods: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. Results: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085–13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41–23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (β = 0.515; 95% CI, 9.712–21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. Conclusion: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

    DOI: 10.1007/s00520-023-07989-9

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  • The Impact of Nutrition and Oral Function Exercise on among Community-Dwelling Older People

    Tani, A; Mizutani, S; Kishimoto, H; Oku, S; Iyota, K; Chu, TS; Liu, X; Kashiwazaki, H

    NUTRIENTS   15 ( 7 )   2023.4   eISSN:2072-6643

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    Oral function (OF) decline in older people is associated with nutritional deficiencies, which increases frailty risk and the need for nursing care. We investigated whether the delivery of an oral function improvement program on a tablet device was as effective as delivery through a paper-based program. We also investigated the association between tongue pressure (TP) improvement and nutritional status at the baseline. The participants involved in the study were 26 community-dwelling older people with low TP, <30 kPa, aged ≥65 years, who were enrolled in a randomized controlled trial for a month in Itoshima City, Fukuoka, Japan. Oral and physical functions and body composition were measured at the baseline and at follow-up. Two-way analysis of variance revealed that body mass index (p = 0.004) increased, and maximum masticatory performance (p = 0.010), maximum TP (p = 0.035), and oral diadochokinesis /pa/ and /ka/ (p = 0.009 and 0.017, respectively) improved in a month. Participants with higher TP improvement showed an increased intake of animal proteins at the baseline: fish (p = 0.022), meat (p = 0.029), and egg (p = 0.009). OF exercises for improving TP were associated with higher animal protein intake at the baseline. This study has been registered with the UMIN Clinical Trials Registry (UMIN 000050292).

    DOI: 10.3390/nu15071607

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  • Association between oral function and physical pre-frailty in community-dwelling older people: a cross-sectional study

    Tani, A; Mizutani, S; Oku, S; Yatsugi, H; Chu, TS; Liu, X; Iyota, K; Kishimoto, H; Kashiwazaki, H

    BMC GERIATRICS   22 ( 1 )   726   2022.9   eISSN:1471-2318

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    Background: Few studies have examined the relationship between oral functions and the physical pre-frailty status, classified using physical function tests. This cross-sectional study aimed to clarify this association among community-dwelling older people from the Itoshima Frail Study in Itoshima Fukuoka Prefecture. Methods: Of the 1,555 individuals invited to join the study, 381 (188 males and 193 females) enrolled. Their physical pre-frailty was assessed with a classification system consisting of two physical indicators (fatigue and unintentional weight loss, determined with a questionnaire), two functional components (declined walking speed and muscle weakness, determined using a body function measuring instrument), and declined physical activity (examined using a triaxial accelerometer). Subsequently, the individuals were classified into three groups: robust, pre-frailty, and frailty. Along with the number of teeth remaining, oral functions, such as masticatory performance, tongue pressure strength, and oral diadochokinesis (ODK), were examined. Data regarding social activity and exercise habits were collected, and the individuals’ body compositions were measured. Odds ratios (ORs) and 95% confidence intervals (CIs) for the physical pre-frailty were calculated using logistic regression models. Results: In this study, 126 (33%) participants presented with physical pre-frailty. The participants in the robust group were younger, had stronger maximum handgrip strength, and walked faster than those in the physical pre-frailty group (p < 0.001). The robust group presented with better oral functions (masticatory performance, p = 0.015; oral ODK /ta/, p = 0.004). The physical pre-frailty status was significantly associated with age (OR, 1.111; 95% CI, 1.048–1.178; p < 0.001), masticatory performance (OR, 0.819; 95% CI, 0.680–0.986; p = 0.035), low ODK/ta/ (OR, 1.864; 95% CI, 1.069–3.250; p = 0.028), and low social activity (OR, 2.273; 95% CI, 1.308–3.951; p = 0.004). Conclusion: This study indicated that older people with higher age, lower anterior tongue movement, lower masticatory performance, and lower social activity are positively associated with physical pre-frailty.

    DOI: 10.1186/s12877-022-03409-5

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  • Primary Teeth-Derived Demineralized Dentin Matrix Autograft for Unilateral Maxillary Alveolar Cleft during Mixed Dentition

    Matsuzawa, Y; Okubo, N; Tanaka, S; Kashiwazaki, H; Kitagawa, Y; Ohiro, Y; Mikoya, T; Akazawa, T; Murata, M

    JOURNAL OF FUNCTIONAL BIOMATERIALS   13 ( 3 )   2022.9   ISSN:2079-4983 eISSN:2079-4983

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    Language:English   Publisher:Journal of Functional Biomaterials  

    This clinical report describes the immediate autograft of primary (milk) teeth-derived demineralized dentin matrix (DDM) granules for a 6-year-old boy with unilateral alveolar cleft. First, four primary teeth were extracted, crushed in an electric mill for 1 min, and the crushed granules were demineralized in 2% HNO3 solution for 20 min. Simultaneously, the nasal mucoperiosteum was pushed upwards above the apices of the permanent central incisor adjacent to the cleft. The nasal and palatal openings were closed by suturing the mucoperiosteum on both sides of the cleft with absorbable threads. The wet DDM granules were grafted into the managed cleft triangle space, and a labial flap was repositioned. The radiographic images at 6 months showed the continuous hard tissues in the cleft area and DDM granules onto lateral incisor (22) and impacted canine (23). The 3D-CT views at 2 years showed impacted tooth (22) blocked by primary canine and the replacement of DDM granules by bone near teeth (22,23). At 4 years, tooth crown (22) was situated just under the mucous membrane, and teeth (22,23) erupted spontaneously until 6 years without a maxillary expansion and a tow guidance of canine. The DDM granules contributed to bone formation without the inhibition of spontaneous tooth eruption. We concluded that autogenous primary teeth DDM graft should become a minimally invasive procedure without bone harvesting and morbidities for unilateral alveolar cleft.

    DOI: 10.3390/jfb13030153

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  • Histological Evidences of Autograft of Dentin/Cementum Granules into Unhealed Socket at 5 Months after Tooth Extraction for Implant Placement

    Murata, M; Kabir, MA; Hirose, Y; Ochi, M; Okubo, N; Akazawa, T; Kashiwazaki, H

    JOURNAL OF FUNCTIONAL BIOMATERIALS   13 ( 2 )   2022.6   ISSN:2079-4983 eISSN:2079-4983

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    The aim of this clinical case study was to observe biopsy tissues at 5 months after an autograft of a partially demineralized dentin/cementum matrix (pDDM) into a tooth-extracted socket exhibiting healing failure. A 66-year-old female presented with healing failure in the cavity for 2 months after the extraction (#36). Initial X-ray photos showed a clear remainder of lamina dura (#36), a residual root (#37), and a horizontal impaction (#38). The vital tooth (#38) was selected for pDDM. The third molar crushed by electric mill was decalcified in 1.0 L of 2.0% HNO3 for 20 min and rinsed in cold distilled water. The pDDM granules (size: 0.5–2.0 mm) were grafted immediately into the treated socket. X-ray views just after pDDM graft showed radio-opaque granules. At 5 months after pDDM graft, the surface of regenerated bone was harmonized with the mandibular line, and bone-like radio-opacity was found in the graft region. The biopsy tissue (diameter: 3.0 mm) at 5 months after pDDM graft showed that mature bone was interconnected with the remaining pDDM. The novel histological evidence highlighted that newly formed bone was connected directly with both dentin-area and cementum-area matrix of pDDM. We concluded that pDDM contributed to the regeneration of bone in the unhealed socket, and this regeneration prepared the socket for implant placement. Autogenous pDDM could be immediately recycled as an innovative biomaterial for local bone regeneration.

    DOI: 10.3390/jfb13020066

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  • Effect of Isometric Tongue Lifting Exercise on Oral Function, Physical Function, and Body Composition in Community-Dwelling Older Individuals: A Pilot Study

    Iyota, K; Mizutani, S; Kishimoto, H; Oku, S; Tani, A; Yatsugi, H; Chu, TS; Liu, X; Kashiwazaki, H

    GERONTOLOGY   68 ( 6 )   644 - 654   2022.6   ISSN:0304-324X eISSN:1423-0003

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    Introduction: It is known that oral frailty is one of the risk factors for physical frailty. Therefore, early detection, appropriate treatment, and prevention of oral frailty are really important. Tongue lifting exercise has been identified as a well-known method for improving decreased tongue pressure, one of the factors for oral frailty. However, few reports have investigated how tongue-strengthening exercises affect physical function and body composition. The aim of this study was to investigate the effects of isometric tongue lifting exercises on oral function, physical function, and body composition. Methods: Participants were 49 elderly people aged 68-79 years, who had previously participated in the "Itoshima Frail Study."Participants performed isometric tongue lift exercises for 3 months. Oral function (tongue pressure and oral diadocokinesis), physical function (grip strength, open-eyed one-leg standing, sit-to-stand motion time, 5-m gait speed, and 3-m Timed up and go [TUG]), and body composition were measured at baseline and post-intervention, and the extent of changes in each item was statistically analyzed. Furthermore, participants were divided into physical frailty/pre-frailty and robust groups based on the Japanese version of the frail scale proposed by [BMC Geriatr. 2015 Apr;15:36] and were compared in terms of the extent of changes in each item baseline and the post-intervention. Results: After the intervention, oral function increased significantly together with a significant improvement in physical function, open-eyed one-leg standing time, sit-to-stand motion, and 3-m TUG. For body composition, visceral fat level and basal metabolic rate decreased significantly. Although no significant change in body composition was observed in the physical frailty/pre-frailty group after the intervention, significant improvements in several items were observed in the robust group. Conclusion: Isometric tongue lifting exercise can effectively improve oral function. Furthermore, it might affect physical function and body composition.

    DOI: 10.1159/000518270

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  • A Case of Dependent Older Adult with Antiresorptive Agent-Related Osteonecrosis of the Jaw Managed by Home-visit Dental Treatment Including Dentures

    Tsutsumi Koshiro, Kashiwazaki Haruhiko

    Ronen Shika Igaku   36 ( supplement )   109 - 113   2022.3   ISSN:09143866 eISSN:18847323

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    Language:Japanese   Publisher:Japanese Society of Gerodontology  

    <p> 緒言:乳癌術後再発骨転移に対してデノスマブを使用し,骨吸収抑制薬関連顎骨壊死(Antiresorptive Agent-Related Osteonecrosis of the Jaw:ARONJ)による腐骨形成を発症した患者に対して,大学病院専門外来と連携して歯科訪問診療にて義歯を作製し,良好な経過を得た1例を経験したので報告する。</p><p> 症例:初診時69歳女性。2016年11月,患者を担当しているケアマネジャーより依頼を受け歯科訪問診療を開始した。同年12月,<img align="middle" src="./Graphics/abst-36-109-5.png"/>相当部周囲歯肉に発赤・排膿を認め,義歯調整・消炎処置を行ったが改善されず,2017年1月,精査加療目的で福岡歯科大学医科歯科総合病院口腔外科(以後,福歯大口腔外科と略す)を紹介受診した。</p><p> 経過:2017年1月,福歯大口腔外科外来にてARONJの診断の下,消炎を目的に左側下顎骨の腐骨を開放創とした。その後,週1回の歯科訪問診療と月1回の福歯大口腔外科受診を並行して義歯調整と消炎処置を継続した。同年6月,露出した腐骨をリリーフする形態で下顎義歯を新製した。9月,福歯大口腔外科入院下で腐骨除去術を実施した。退院後も歯科訪問診療を継続し,2018年5月,下顎義歯をリライニングしてさらなる適合改善を図った。その結果,以前より摂取可能な食物が増えて体重増加を認めた。</p><p> 考察:ARONJを伴う要介護高齢者に対して,地域歯科医院による歯科訪問診療と大学病院の専門外来との連携を取ることで,義歯作製および腐骨除去は可能であった。適切な病診連携により要介護高齢者のQuality of Lifeを維持できることが示唆された。</p>

    DOI: 10.11259/jsg.36.supplement_109

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  • A cross-sectional study of age-related changes in oral function in healthy Japanese individuals Reviewed

    Kiyomi Iyota, Shinsuke Mizutani, Saori Oku, Misa Asao, Toshiko Futatsuki, Ryosuke Inoue, Yuko Imai, Haruhiko Kashiwazaki

    International journal of environmental research and public health   17 ( 4 )   2020.2

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    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.

    DOI: 10.3390/ijerph17041376

  • Dominant-negative p53 mutant R248Q increases the motile and invasive activities of oral squamous cell carcinoma cells Reviewed

    Seitaro Nakazawa, Ken Ichiro Sakata, Shanshan Liang, Kazuhito Yoshikawa, Hisashi Iizasa, Mitsuhiro Tada, Jun Ichi Hamada, Haruhiko Kashiwazaki, Yoshimasa Kitagawa, Yutaka Yamazaki

    Biomedical research (Tokyo, Japan)   40 ( 1 )   37 - 49   2019.1

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    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.

    DOI: 10.2220/biomedres.40.37

  • Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD Reviewed

    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

    International journal of hematology   104 ( 1 )   117 - 124   2016.7

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    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.

    DOI: 10.1007/s12185-016-1996-0

  • Relationship between acetaldehyde concentration in mouth air and tongue coating volume Reviewed

    Aya Yokoi, Takayuki Maruyama, Reiko Yamanaka, Daisuke Ekuni, Takaaki Tomofuji, Haruhiko Kashiwazaki, Yutaka Yamazaki, Manabu Morita

    Journal of Applied Oral Science   23 ( 1 )   64 - 70   2015.1

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    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.

    DOI: 10.1590/1678-775720140223

  • Factors associated with dry mouth in dependent Japanese elderly Reviewed

    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

    Gerodontology   31 ( 1 )   11 - 18   2014.3

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    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.

    DOI: 10.1111/j.1741-2358.2012.00685.x

  • Bone augmentation using novel unidirectional porous hydroxyapatite with bone morphogenetic protein-2 on rat skull Reviewed

    Haruhiko Kashiwazaki, Naoki Harada, Toshiyuki Akazawa, Md Arafat Kabir, Yasuhito Minamida, Masaru Murata

    Journal of Hard Tissue Biology   22 ( 3 )   337 - 342   2013.7

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    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.

    DOI: 10.2485/jhtb.22.337

  • Surface structure and biocompatibility of demineralized dentin matrix granules soaked in a simulated body fluid Reviewed

    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

    Applied Surface Science   262   51 - 55   2012.12

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    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.

    DOI: 10.1016/j.apsusc.2012.01.053

  • Construction and characterization of a tissue-engineered oral mucosa equivalent based on a chitosan-fish scale collagen composite Reviewed

    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

    Journal of Biomedical Materials Research - Part B Applied Biomaterials   100 B ( 7 )   1792 - 1802   2012.10

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    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.

    DOI: 10.1002/jbm.b.32746

  • Relationship between subjective assessment of oral health and medical expenses in community-dwelling elderly persons Reviewed

    Eriko Harada, Shingo Moriya, Ayumi Murata, Masumi Muramatsu, Haruhiko Kashiwazaki, Kunihiko Kobayashi, Kenji Notani, Nobuo Inoue

    Gerodontology   29 ( 2 )   e246 - e252   2012.6

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    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.

    DOI: 10.1111/j.1741-2358.2011.00459.x

  • A comparison of oral mucositis in allogeneic hematopoietic stem cell transplantation between conventional and reduced-intensity regimens Reviewed

    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

    Supportive Care in Cancer   20 ( 5 )   933 - 939   2012.5

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    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.

    DOI: 10.1007/s00520-011-1164-2

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MISC

  • Oral disease and malnutrition in the elderly - impact of oral cancer.

    Hassan NMM, Akhter R, Staudinger L, Tarpey N, Basha S, Cox S and Kashiwazaki H.

    Curr Oral Health Rep   2017.4

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

Professional Memberships

  • Japanese Society of Gerodontology

Committee Memberships

  • 国際口腔ケア学会   Executive   Foreign country

    2021.6 - 2023.6   

  • 日本老年歯科医学会   Executive   Domestic

    2018.7 - 2020.7   

Academic Activities

  • 日本老年歯科医学

    2019.7 - 2021.7

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    Type:Academic society, research group, etc. 

Research Projects

  • データ駆動型解析を用いた口腔からアプローチするフレイル・生活習慣病予防法の開発

    Grant number:24K02766  2024 - 2027

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • Development of Oral Function Improvement Program for Prevention of Frail Using IoT

    Grant number:20K10269  2020 - 2022

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kashiwazaki Haruhiko

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    Authorship:Principal investigator  Grant type:Scientific research funding

    From the viewpoint of extending healthy life expectancy, it is an urgent issue in Japan to prevent frailty. Though the improvement of oral frailty seems to make the aid of the frailty prevention, there is no clear evidence. The purpose of this study is to develop a "Oral rail prevention and improvement program" to prevent frailty, to construct a training and guidance system using IoT, and to verify the frailty preventive effect of the new program for local elderly residents. It aims at the establishment of the evidence that the health of the oral cavity is connected with the extension of healthy life.

    CiNii Research

Educational Activities

  • 高齢者歯科学・全身管理歯科学に関する教育活動を行っている。

Class subject

  • 高齢者歯科学

    2024.10 - 2025.3   Second semester

  • 歯科全身管理学1

    2018.4 - 2018.9   First semester

Other educational activity and Special note

  • 2023  Class Teacher  学部

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Dentistry / Social Dentistry

Clinician qualification

  • Preceptor

    日本口腔外科学会

  • Preceptor

    日本老年歯科医学会

  • Preceptor

    Japanese Stomatological Society(JSS)

Year of medical license acquisition

  • 2018