Showa Univ J Med Sci 2（8 4）, 393～420, December 2016

Proceedings of the 63rd General Meeting of the Showa University Society

entity of IgG4-RD, has been reported to give rise to Educational Lecuture malignant neoplasms, including PDAC, and Type Ⅰ AIP Diagnosis and Treatment of Pancreatic Diseases, often relapses, alternative treatments are required and Including Presentation of Latest Concepts are being developed.

Hitoshi YOSHIDA Key words: chronic pancreatitis, autoimmune pancreatitis, Department of Medicine, IgG4-related disease, pancreatic ductal ade- Division of Gastroenterology, nocarcinoma, intraductal papillary mucinous Showa University School of Medicine neoplasm

Pancreatic diseases include pancreatitis and pancreatic Role of Fibroblast Cell Contraction in Wound neoplasms （PN）. Pancreatitis is induced by digestion Healing Processes of the pancreas itself. Japanese clinical criteria for ― Mechanisms of Contractile Responses Using 3-D chronic pancreatitis （CP） distinguish CP from both Reconstituted Fibroblast Fibers― autoimmune pancreatitis（ AIP ; Type Ⅰ, an IgG4-related Koji NOBE disease ［IgG4-RD］; Type Ⅱ, occasionally associated Department of Pharmacology, with inflammatory bowel disease） and conclusive duct Toxicology and Therapeutics, pancreatitis derived from pancreatic cancer. PNs, in Division of Pharmacology, particular pancreatic ductal adenocarcinoma （PDAC）, Showa University School of Pharmacy so-called pancreatic cancer, are mostly associated with fatal outcomes. In July 2016, National Cancer Institute Fibroblast cells play a central role in the proliferation disclosed that results of estimates of five-year survival phase of wound healing processes, contributing to force rate for Japanese people suffering from all malignant development: however, the regulatory mechanisms neoplasms had become first beyond 60％ from 2006 are not well known. We used a reconstituted fiber through 2008. Conversely, the survival rate for （ broblast ber） formed by growing NIH 3T3 broblast pancreatic cancer, including PDAC, was 7.7％, the lowest cells in type-1 collagen to characterize non-muscle value. Classification of Pancreatic Carcinoma, Japan contractility and the intracellular signaling pathway Pancreas Society were revised and published as the 7th involved in wound healing. Addition of calf serum edition in 2016. T-classification representing size of （CS） to the fibers elicited reversible contractures that tumor was classi ed based on in ltration to SMA and were repeated for ＞ 8 h. CS elicited dose-dependent celiac artery according to surgery aspect. Consistency increases in isometric force, with 30％ CS producing with the international standard was clarified about the largest force （106 ± 12 µN ; n ＝ 30）. From this, the staging classification, and pathohistologic classification force per cell cross-sectional area was estimated to be was described as differentiation types. Since intraductal 0.5 mN/mm2. CS （30％） induced a sustained broblast papillary mucinous neoplasm （IPMN） rst put forward fiber contraction that was accompanied by a transient 2＋ from Japan had been investigated and widely studied, increase in intracellular calcium concentration （［Ca ］i）. international consensus guidelines for the management However, pre-treating the fibroblast fibers with of IPMN and mucinous cystic neoplasm （MCN） was calcium channel blockers and protein kinase 2＋ revised 2012. IgG4-RD was assigned as an intractable inhibitors had no effect on contractions or ［Ca ］i. disease because the patient estimation increased and In contrast, Rho kinase, a key element in the reached 26,000 peoples. Because AIP, the representative Ca2＋-independent intracellular signaling pathway, 394 Proceedings of the 63rd General Meeting of the Showa University Society

was involved in CS-induced fibroblast fiber patients are more valuable than Walk-in patients with contraction. The Rho kinase inhibitor Y-27632 regard to management of acute hospitals. depressed the CS-induced contractions in a dose- In this lecture, I will discuss the relationship between 2＋ dependent manner without affecting the ［Ca ］i new hospital patients and hospital management in the response. Rho kinase also enhanced actin stress ber acute hospital setting, and hope I can provide you with （ASF） formation: this was also suppressed by Y-27632. a strategy for gaining more Referred patients. We conclude that Rho kinase activation can regulate Key words: hospital management strategy, patient re - wound healing processes that are mediated by broblast ferral, hospitalized patient cell contraction. These ndings may contribute to the Original Sessions arti cial regulation of wound healing processes in scar tissues. 1． Review of the Showa University Head and Neck Key words: wound healing, broblast cells, collagen, non- Oncology Center 1, 2） 1, 2） muscle contraction, rho kinase Shunya EGAWA , Yukiomi KUSHIHASHI , 1, 2） 1, 3） Kenichiro IKEDA , Yuya KURASAWA , 1, 3） 1, 3） A Strategy for Gaining New Hospital Patients in Atsutoshi YASO , Hideyuki KATSUTA , 4） 2） Acute Hospitals Tatsuo SHIROTA , Hitome KOBAYASHI , 1, 2, 3） Yumi KAMIJO Toshikazu SHIMANE Showa University 1） Head and Neck Oncology Center, Graduate School of Health Sciences Showa University 2） Department of Otorhinolaryngology, There is a positive correlation between increases Showa University School of Medicine in inpatient numbers with improvements in hospital 3） Department of Oral and Maxillofacial Surgery, management ; however, this correlation has not been Division of Oral Oncology, well studied. The purpose of this study was to devise Showa University School of Dentistry a strategy for gaining new hospital patients for acute 4） Department of Oral and Maxillofacial Surgery, hospitals. Division of Craniofacial Surgery, Patients are encouraged to see clinical specialists; Showa University School of Dentistry therefore, collaborations between hospitals and local clinics is important so that continuity in health It has been one year since a team of doctors in the and medical services is maintained for all patients. Otorhinolaryngology and Dentistry and Oral Surgery However, encouraging the transfer of patients from established the Showa University Head and Neck acute hospitals to rehabilitation and chronic hospitals Oncology Center. This center inspects, diagnoses, and has led to shortened lengths of stay at acute hospitals, treats head/neck and oral diseases by cooperating resulting in fewer patients. Due to the high turnover Otorhinolaryngology and Oral Surgery. The Oral rate of hospitalized patients in acute medical institutes, Health Care Center also offers oral rehabilitation it is necessary to admit new patients to keep patient to address pronunciation or swallowing issues in the numbers constant. Here, we propose a strategy for perioperative period as well as treatments focused maintaining patient numbers in the acute hospital on patient quality of life （QOL）. In this study, we setting. compared cases of head and neck tumors between Patients are divided into those with a referral those diagnosed during one year before and after （Referred patients） and those without a referral （Walk- establishing the center. There were 232 cases of head in patients） during their initial medical examination. and neck tumors in 2015 compared with 155 cases in Referred patients are more likely to be admitted into 2014 （increase of 149.7％）; benign tumors increased in hospital than Walk-in patients. Referred patients are number from 68 to 92 cases （135.2％） while malignant more likely to undergo operations and receive highly tumors were increased from 87 to 140 cases （160.9％）. advanced medical treatment. Therefore, Referred The average number of hospitalization days was 20.9 Proceedings of the 63rd General Meeting of the Showa University Society 395 days in 2015 as compared with 25.8 days in 2014. In changes such as sternotomies required in any more detail, there were 60 cases of oral cancer in case. Postoperative pathological diagnosis showed 2015 compared to 8 cases in 2014 （750％ increase）. adenomatous goiter in three patients and follicular With respect to treatment method, 87 cases underwent adenoma in one patient, with all diagnosed as benign. surgery in 2015 compared to 26 cases in 2014 （327％ Surgery with neck dissection was deemed suitable for increase）. In conclusion, oral cancer diagnoses increased the cases presented herein. We therefore recommend in number after establishing this center, and accordingly, consulting with the departments of thoracic surgery the percentage of surgical treatment cases per total and cardiovascular surgery when preparing for similar patients also increased. This outcome could lead to cases such as those with malignant tumors, dif culty in shortened hospitalizations. enucleation, or unexpected bleeding. Key words: oral oncology, team medical care, head and Key words: mediastinal goiter, mediastinal goiter surgery, neck oncology center thyroid surgery, neck dissection

2． A Study on Mediastinal Goiter Patients Who 3． A Prospective Observational Study of Patients’ Had Surgery at Our Newly Established Medical Quality of Life and Risk Factors of Chemotherapy- Center induced Nausea and Vomiting in Patients with 1, 2） 1, 3） Yukiomi KUSHIHASHI , Hideyuki KATSUTA , Breast Cancer Undergoing Highly Emetogenic 1, 2） 1, 3） Kenichirou IKEDA , Atsutoshi YASO , Chemotherapy 1, 2） 2） 1, 2） 2） Syunya EGAWA , Yoichi IKENOYA , Jumpei TOKUMARU , Satoko HANDA , 1, 3） 1, 3） 2） Yuya KURASAWA , Yoshiro SAITO , Yasuhisa KATO 2） 1, 2, 3） 1） Hitome KOBAYASHI , Toshikazu SHIMANE Department of Pharmacy, 1） Head and Neck Oncology Center, Yokohama City University Medical Center Showa University Hospital 2） Department of Drug Information, 2） Department of Otorhinolaryngology, Division of Drug Information Analytics, Showa University School of Medicine Showa University School of Pharmacy 3） Department of Oral and Maxillofacial Surgery, Division of Oral Oncology, Chemotherapy-induced nausea and vomiting （CINV） Showa University School of Dentistry deteriorates patients’ quality of life （QOL）, although newly developed antiemetic drugs have helped We report herein four cases of mediastinal goiter alleviate CINV. Young age, female sex, and a history surgery treated in the one year and 10 months after the of morning sickness, motion sickness, or no alcohol opening of our center to July 31, 2016, comprising 5.9％ consumption are patient-related risk factors associated of all thyroid surgeries during that period. The four with CINV. Most breast cancer patients are young and goiter patients ranged in age from 56 to 68 years old, female and thus have a high risk of CINV ; however, with an average age of 61.8 years and a male to female data are limited regarding the QOL of patients ratio of 1：3. All these patients underwent needle receiving a novel antiemetic regimen and the impact aspiration biopsies, with 3 cases found to be normal or of emetogenic risk factors on QOL. This prospective benign, and one case deemed indeterminable. Surgical observational study therefore investigated patients’ stress can enhance tumor growth, thus we chose prompt QOL and the effect of CINV risk factors on QOL in surgical treatment for all cases using neck dissection. breast cancer patients receiving a novel antiemetic drug We consulted with the departments of thoracic surgery regimen （aprepitant, palonosetron, and dexamethasone） and cardiovascular surgery to prepare for the cases, while undergoing highly emetogenic chemotherapy. The including for the difficulty posed by enucleation or primary endpoint was the proportion of patients with unexpected bleeding. no impact on their QOL during the 120-hour period Postoperative recurrent nerve paralysis was not after chemotherapy. Among the 99 patients evaluated, observed in any cases, nor were surgical procedure 46.5％ showed no change in their QOL. Among the 396 Proceedings of the 63rd General Meeting of the Showa University Society

patients who developed CINV symptoms, the proportion signi cantly higher in CD44＋ cells exposed to paclitaxel of patients with decreased QOL was 89.3％ and 96.8％ than CD44- cells, suggesting that paclitaxel more of those who experienced vomiting and significant strongly induced apoptosis than the other anticancer nausea, respectively. The number of CINV risk factors drugs. The findings suggested that p21 expression is was inversely correlated with the complete response associated with miRNA levels in CD44＋ cells after rate and QOL. The results of this study elucidate the exposure to paclitaxel. effects of nausea and vomiting on QOL, and indicate Key words: TNBC, miRNA, breast cancer, p21 that patients with CINV risk factors may need further symptom management. 5． ADAMTS16 Mutations Sensitize Ovarian Cancer Key words: chemotherapy-induced nausea and vomiting, Cells to Platinum-based Chemotherapy

breast cancer, quality of life, risk factor Maya YASUKAWA Department of Obstetrics and Gynecology, 4． Suppression of p21 Expression by Increased miR- Showa University School of Medicine 93 in CD44-positive MDA-MB-231 Cells after Exposure to Paclitaxel Purpose 1） 1） Kentaro IIJIMA , Akiko SASAKI , Ovarian cancer is one of the most lethal malignant 2） 1） Yuko TSUNODA , Mayumi TSUJI , tumors in women, and the prognosis of affected 1） 1） Hideto OYAMADA , Hiromichi TSUCHIYA , patients depends, in part, on their response to platinum- 1） 1） Yuko UDAKA , Kanji FURUYA , based chemotherapy. Our recent analysis of genomics 1） 1） Hokuto NAMBA , Toshihiko GOCHO , and clinical data from the Cancer Genome Atlas 1） 1） Katsuji OGUCHI , Yuji KIUCHI demonstrated that somatic mutations of ADAMTS16 1） Department of Pharmacology, along with several other members of the ADAMTS Showa University School of Medicine family were associated with improved sensitivity to 2） Kameda Medical Center, Breast Center platinum and better survival in patients with ovarian cancer. However, the functional role of these mutations Breast cancer is the most prevalent cancer in in ovarian cancer cells is largely unknown. women. The hormone receptors, estrogen receptor Experimental design （ER） and progesterone receptor （PgR）, as well as We performed in vitro studies to compare functional epidermal growth factor receptor （HER2） are often effects of the six identified ADAMTS missense highly expressed in breast cancer cells, but are absent in mutations on the platinum sensitivity of ovarian cancer 10-15％ of all cases of breast cancer, known as triple- cells. We also used a well-characterized in vivo mouse negative breast cancer （TNBC）. The prognosis of model to evaluate the response of ovarian cancer cells TNBC patients is poor and 30％ of patients experience with ADAMTS16 mutations to platinum-based therapy. recurrence and distant metastasis. Herein we examined Results the p21 and glutathione metabolic pathways in CD44 Exogenously expressed ADAMTS16 missense mutations -positive or -negative cultured MDA-MB-231 breast inhibited cell growth or sensitized tumor cells to cisplatin cancer cells（ CD44＋ or CD44- cells） after exposure to and inhibited migration and invasion. Orthotopic xenograft tubulin inhibitors, paclitaxel and eribulin, and a platinum experiments showed that mice injected with ovarian cancer agent, cisplatin, to identify microRNA （miRNA）- cells that exogenously expressed ADAMTS16 mutations inhibiting p21 expression, a factor causing treatment had a better response to cisplatin treatment. resistance. After exposure to an anticancer drug at Conclusion 1 nM for 24 hours, CD44＋ cells were extracted to These functional studies indicate that mutations of measure p21, glutathione, caspase-3, and miRNA levels. ADAMTS16 might actively contribute to therapeutic Expression of miRNAs, miR-20a, and miR-93 increased response in ovarian cancer. after exposure to paclitaxel in CD44＋ cells compared Key words: ovarian cancer, platinum sensitivity, with untreated cells. The caspase-3 expression level was ADAMTS16 Proceedings of the 63rd General Meeting of the Showa University Society 397

6． Study of Cognitive Functions Ef caciously Affected Results and discussion by Psychoeducational Program for Patients with Our results showed that psychoeducation program led Schizophrenia to improvements in global functioning, Consciousness of 1, 2） 3） Tomohiro IKEDA , Koji HORI , disease, and medication adherence. And the possibility 1, 4） 1, 5） Atsuko INAMOTO , Takuro NAKATSUBO , that executive function and working memory were 1, 6） 7） Junko KOIKE , Satoru SUGISAWA , related to the improvement of the general function was 1, 2） 8） Toshiaki TSUNEOKA , Masaru MIMURA , suggested. 1, 2） Akira IWANAMI The patients whom a general function did not 1）Department of Psychiatry, improve by a program refused it flatly for a way of Showa University School of Medicine thinking for oneself, and it was inferred that the effect 2）Department of Psychiatry, was hard to be obtained by a characteristic not to be Showa University Karasuyama Hospital able to notice that there were other choices well. 3）Department of Psychiatry, Conclusion St.Marianna University School of Medicine On the basis of these results, future studies are 4）Department of Psychiatry, warranted to improve our program and con rm its long- Showa University Northern Yokohama Hospital term effectiveness. 5）Department of Psychology, ows that cognitive function is the critical factor Shukutoku University School of Welfare affecting readmission. 6） Department of Nursing, Key words: neuropsychological tests, schizophrenia, School of Health Care, psychoeducational programs, cognitive International University of Health and Welfare function 7） Department of Hospital Pharmaceutics, Showa University School of Pharmacy 7． Cilostazol Suppresses Amyloid β （Aβ）-induced 8） Department of Neuropsychiatry, Neuro toxicity by Inhibiting Oxidative Stress Keio University School of Medicine and the Extracellular Signal-regulated Kinase/ Phosphorylated cAMP Response Element-binding Background Protein Pathway

Psychoeducational programs have become relatively Tatsunori OGUCHI, Ran ONO, standardized for patients with schizophrenia, although Mayumi TSUJI, Katsuji OGUCHI, data correlating the effectiveness of such programs Yuji KIUCHI and cognitive function are limited. To the best of Department of Pharmacology, our knowledge, no such studies have been reported in Showa University School of Medicine Japan. Methods Alzheimer’s disease （AD） is characterized by Participants included 91 patients with schizophrenia progressive cognitive impairment. The histopathological （women, n ＝ 46 ; men, n ＝ 45 ; mean age, 43.2 years） hallmarks of an AD brain are deposition of amyloid β admitted to a subacute care unit in Showa University （Aβ） plaques and intracellular neurofibrillary tangles, Karasuyama Hospital and who had given their consent the loss of neurons, and high levels of oxidative stress. to participate. In this study, a new psychoeducation- Cilostazol （CSZ） has been shown to be more bene cial based, psychosocial intervention program （the Program） in the maintenance and improvement of memory was initiated. The effectiveness of the Program was function in AD patients taking donepezil. The aim evaluated by Global Assessment of Functioning （GAF） of the present study was to elucidate the underlying scale and four scales. And we measured a cognitive signaling pathway by which CSZ protects against Aβ function between improvement group and non- （1-42）-induced oxidative stress-mediated apoptosis in improvement group of GAF. SH-SY5Y cells. At a concentration of 2.5 µM, Aβ（1-42） increased 398 Proceedings of the 63rd General Meeting of the Showa University Society

both the generation of reactive oxidative species （ROS） underlying signaling pathway by which propofol, at and the activity of p38 the mitogen-activated protein a clinically relevant concentration, protects against A kinase （p38 MAPK） and extracellular signal-regulated β（1-42）-induced neurotoxicity in SH-SY5Y cells. kinase （ERK）, as well as caspase-3 in the cytosol. SH-SY5Y cells differentiated by retinoic acid were These Aβ（1-42）-induced increases were significantly pretreated with 1 µM propofol for 1 h before being reduced by CSZ （2.5 µM） pretreatment, but not by treated with 2.5 µM Aβ（1-42）. In cells with Aβ- 2＋ 2＋ ERK phosphorylation. Furthermore, CSZ pretreatment induced neurotoxicity, intracellular Ca （［Ca ］i） suppressed Aβ（1-42）-induced apoptosis and improved levels, caspase-3 and MAPKs （c-Jun N-terminal kinase cell viability via downregulation of Bax, a proapoptotic ［JNK］ and p38 MAPK） activity, and tau protein protein, expression of NADPH oxidase 4 （NOX4）, and phosphorylation were all increased. However, propofol upregulation of Bcl-2, an antiapoptotic protein. Thus, pretreatment significantly reduced these effects of A CSZ may attenuate Aβ-induced oxidative stress by β（1-42）. These results demonstrate that propofol 2＋ inhibiting signaling pathways mediated by MAPK. decreases ［Ca ］i and suppresses p38 MAPK and JNK These findings suggest that CSZ could ameliorate activity, as well as tau protein hyperphosphorylation, neurotoxicity through multiple mechanisms, one of which thus preventing the development of Aβ-induced involves attenuation of oxidative stress by suppressing neurotoxicity in SH-SY5Y cells. NOX4 in Aβ-induced apoptosis and another that Key words: propofol, amyloid β protein, p38 MAPK, involves an antiapoptotic effect via the ERK/ intracellular Ca2＋, Alzheimer’s disease phosphorylated cAMP response element-binding protein （pCREB） pathway. 9． Behavioral and Omics Analyses Study on Key words: cilostazol, amyloid β, alzheimer’s disease, Potential Involvement of Dipeptide Balenine oxidative stress, ERK Through Supplementation in Diet of Senescence- accelerated Mouse Prone 8． Propofol Prevents Amyloid β-Induced Neuro- Satoru YAMANAKA toxicity by Suppressing Intracellular Ca2＋ and Depertment of Biochemistry, P38 Mitogen-activated Protein Kinase Activity in Showa University School of Medicine SH-SY5Y Cells

Ran ONO, Tatsunori OGUCHI, The present study investigated the effects of Mayumi TSUJI, Katuji OGUCHI, supplementation with the dipeptide balenine, a major Yuji KIUCHI component of whale meat extract （WME）, in the Department of Pharmacology, senescence-accelerated mouse prone 8 （SAMP8） Showa University School of Medicine mouse line, a model of Alzheimer’s disease （AD）, on learning and memory formation, as well as whole-brain Alzheimer’s disease （AD） is the most prevalent form gene expression profiles. Mice fed an experimental of dementia and is characterized by the accumulation balenine-supplemented （＋WME） diet for 26 weeks and deposition of amyloid β protein （Aβ） in the were subjected to behavioral tests to examine effects brain. Aβ increases mitogen-activated protein kinase on learning and memory. In addition, the brain （MAPK） activity and induces neurotoxicity. Some transcriptome of ＋WME-fed SAMP8 was compared inhalation anesthetics, such as isoflurane, have been with that of mice fed the control low-safflower oil suggested to induce Aβ accumulation and cause （LSO） diet using a 4×44K mouse whole-genome DNA AD-like neuropathology. In contrast, propofol, which microarray chip. The WME diet not only induced is used as intravenous anesthetic, has been reported improvements in learning and memory formation, to have neuroprotective effects. However, the precise but also positively modulated changes in the brain mechanism by which propofol protects against Aβ- of SAMP8 mice; the gene inventories are publicly induced neurotoxicity remains unknown. Therefore, available for analysis by the scientific community. the purpose of the present study was to elucidate the Interestingly, the SAMP8 model presented many Proceedings of the 63rd General Meeting of the Showa University Society 399 genetic characteristics of AD, and DNA microarray inspiratory activity were investigated at concentrations and bioinformatics analyses revealed numerous novel of 1-200 µM. In addition, we also examined the effects molecules （Slc2a5, Treh, Fbp1, Aldob, Ppp1r1a, DNase1, of riluzole on seizure-like activity induced by treatment Agxt2 l1, Cyp2e1, Acsm1, Acsm2, and Pah） that were with 20 µM TBOA （a glutamate uptake blocker） or oppositely regulated or recovered compared with the 10 µM bicuculline plus 10 µM strychnine solution. senescence-accelerated mouse resistant 1 （SAMR1） Results mouse line following feeding of the ＋WME diet. The Riluzole caused a dose-dependent decrease in the C4 present study used an experimental strategy to burst rate. Drive potential of the pre-inspiratory demonstrate the effects of the dipeptide balenine, which neurons decreased in a dose-dependent manner after is contained in whale meat, on SAMP8, providing new the application of 50-100 µM riluzole. We also insights into whole-brain changes in the transcriptome. observed a significant decrease in negative slope

The gene expression data will be a valuable resource in conductance, an indicator of INAP, after the application examining the effects of natural products, and could also of riluzole. Seizure-like activity was significantly serve as a human model for further functional analysis attenuated by pretreatment and co-application of a low and investigation. concentration of riluzole （10 µM）, whereas respiratory Key words: whale meat, balenine, dementia, preventive suppression was not observed. effect Conclusion The present study revealed that riluzole effectively

10． Mechanism of the Inhibitory Effects of Riluzole decreases seizure-like activity by possibly blocking INAP on Neuronal-burst Generation at lower concentrations than those inducing respiratory 1） 1） Shihtien LIN , Noriko KOYAMA , depression. 1） 1） Masayuki OHBAYASHI , Yasuna KOBAYASHI , Key words: riluzole, persistent sodium current, seizure- 1） 2） Toshinori YAMAMOTO , Hiroshi ONIMARU , like activity 1） Mari KOGO 1） Department of Clinical Pharmacy, 1 1．withdrawal Division of Pharmacotherapeutics, Showa University School of Pharmacy 12． Optogenetic Analysis of Respiratory Modulation 2） Department of Physiology, Related to Anxiety 1） 1） Showa University School of Medicine Naoki OKUMA , Mitsuko KANAMARU , 2） 2） Satoru ARATA , Jun WATANABE , 1） 1） Introduction Toshiyuki ENDOU , Akira YOSHIKAWA , ＋ 1） 1） It is known that riluzole blocks persistent Na Makito IIZUKA , Masahiko IZUMIZAKI 1） current （INAP）, inhibits generation of neuronal bursts Department of Physiology, and decreases glutamate-induced excitotoxicity. In the Showa University School of Medicine present study, we examined the effects of riluzole on 2） Center for Biotechnology, Showa University respiratory-burst generation and drug-induced seizure-like activity using isolated brainstem-spinal cord preparations Breathing plays an important role in maintaining from newborn rats. homeostasis in the body. It is well documented that Methods breathing patterns are affected by one’s emotions, such The brainstem and spinal cord were isolated from as anxiety and fear. However, the mechanism by which 0-3-day-old rats after deep anesthesia with isoflurane emotion affects respiration has not yet been clearly and then superfused at a rate of 3.0 ml/min with identified. Conversely, research has contributed to oxygenated artificial cerebrospinal fluid. Inspiratory our understanding of the relationship between anxiety/ activity corresponding to phrenic nerve activity was fear and brain monoaminergic neurons. In recent monitored from the fourth cervical ventral root （C4）. years, it has been reported that selective excitement The effects of a 15-min bath application of riluzole on of serotonin （5-hydroxytryptamine ; 5-HT） neurons in 400 Proceedings of the 63rd General Meeting of the Showa University Society

the median raphe nucleus （MRN） increases innate volume in one second （FEV1）, ％FEV1, FEV1％, a anxiety. Consequently, we studied the effects of forced expiratory flow at the FVC 50％（％50）, selective activation of 5-HT neurons in the MRN on and a forced expiratory flow at the FVC 25％（25） respiration as well as on innate anxiety. Experiments were measured using spirometry. In addition, using were performed in genetically modi ed mice expressing MostGraph, resistance was measured at 5 and 20 Hz a channelrhodopsin-2 variant （ChR2 ［C128S］; a （R5 and R20, respectively）, R5-R20, and reactance at 5 step-function opsin） in central 5-HT neurons. Light Hz （X5）, the frequency of resonance （Fres）, and low- stimulation of free-moving mice was applied using a frequency reactance area （ALX） were determined. The Teleopto stimulator through an optical fiber inserted relationship between the spirometry and Mostgraph in the MRN. The innate anxiety was evaluated by was assessed. time spent in the open arm of an elevated plus maze, Results and respiratory variables were measured using a whole The FOT parameters measured by MostGraph were body plethysmograph. With optical stimulation of 5-HT signi cantly correlated with ％FEV1 and FEV1％ （p ＜ neurons in the MRN, time spent in the open arm of 0.001）, with Fres showing the strongest association. We the elevated plus maze was shortened and respiratory found the ratio of the anteroposterior values of FEV1％ rate increased, without a change in tidal volume. These and Fres during an observation period on the basis of results suggest that 5-HT neurons in the MRN elicit a first inspection level. Consequently, the correlation innate anxiety accompanying increased respiratory rate. between FEV1％ and Fres was the highest（ p ＜ 0.001）. Key words: anxiety, respiration, optogenetics, serotonin, Conclusion channelrhodopsin-2 In the asthmatic patients Fres changed more

thanFEVl％．Fres at initial diagnosis is ≤15 Hz in 13． Usefulness of Forced Oscillation Technique in patients with mild asthma, suggesting that changes in Adult Patients with Bronchial Asthma the ratio of the before and after values of Fres during 1） 1） Yosuke HAGIWARA , Keita KASAHARA , observation are a useful indicator for the evaluation of 1） 1） Yusuke KURODA , Haruna MOROHOSHI , asthma. 1） 1） Kyoko FUJISAKI , Kazuya HORIUCHI , Key words: asthma, forced oscillation technique, most- 1） 1） Shigeru TANZAWA , Gen ISHII , graph, spirometry 2） Yusuke SHIKAMA 1） Respiratory Disease Center, 14． Experience of Combined Therapy with Pulmonary Showa University Northern Yokohama Hospital Rehabilitation and Waon Therapy in Patient with 2） Department of Respirology, Chronic Respiratory Failure 1） 2） Showa University Fujigaoka Hospital Hidetsugu TATENO , Yoshitaka ISO , 1） 3） Etsushi KYUNO , Naoko IKEDA , 1） 1） In recent years there has been a focus on the use Go KOIZUMI , Ayaka NOGI , 1） 1） of the forced oscillation technique （FOT） method to Eri KAWASHIMA , Kazuhiro ITAYA , 1） 4） analyze respiratory resistance and reactance. The release Hiroo ICHIKAWA , Yusuke SHIKAMA , 2） of a new FOT machine, the MostGraph, has increased Takeyuki SANBE the ability to conduct FOT analysis in the treatment 1） Department of Internal Medicine, of asthma. The present study evaluated correlations Showa University Fujigaoka between spirometry and respiratory resistance, revealing Rehabilitation Hospital a useful indicator of FOT for the control of asthma. 2） Showa University Methods Research Institute for Sport and Exercise Sciences The medical records of 55 asthma patients who 3） Department of Cardiology, attended Showa University Northern Yokohama Showa University Koto Toyosu Hospital Hospital were evaluated. In each subject, respiratory 4） Department of Respirology, function, vital capacity （VC）, ％VC, forced expiratory Showa University Fujigaoka Hospital Proceedings of the 63rd General Meeting of the Showa University Society 401

In Showa University Fujigaoka Rehabilitation hospital, correlated with changes in quality of life（ QOL）. comprehensive rehabilitation is provided, including Purpose exercise therapy, physical therapy, diet therapy, and The present study was aimed to clarify effects of patient education. Pulmonary rehabilitation for patients cardiac rehabilitation on physical capacity and QOL in with chronic respiratory failure is one of the main patients with acute coronary syndrome（ ACS）. medical treatments. Methods Waon therapy has been reported to be an effective The study enrolled 17 male patients with ACS and safe non-medicinal therapy for patients with aged of 65.9 ＋/- 12.9 years, who participated in a chronic heart failure. By raising core body temperature 5-month outpatient cardiac rehabilitation program. by approximately 1°C using a 60°C dry sauna, it is Cardiopulmonary exercise capacity was measured by possible to reduce the anterior and posterior load of cardiopulmonary exercise tests and QOL was evaluated the heart, to increase cardiac output because of the by subjective health values using the SF-36v2 before peripheral vasodilation, and to improve peripheral and after the cardiac rehabilitation program. vascular endothelial function. However, there are few Results reports regarding Waon therapy in diseases other than Age-adjusted predicted values of exercise capacity chronic heart failure, and its effects in other diseases significantly increased from 67.9％ to 75.6％. Both have not been established. Thus, we trialed combination physical and mental components of QOL significantly treatment with pulmonary rehabilitation and Waon increased （from 38.9 to 45.8, and from 51.7 to 56.6, therapy in a patient with chronic respiratory disease. respectively）, whereas social components significantly The patient was an 84-year-old man with chronic and unexpectedly decreased （from 54.7 to 36.5）. No obstructive pulmonary disease （COPD）. The patient significant relationship was observed between increases had been diagnosed with COPD at 69 years of in exercise capacity and changes in any components of age and, thus far, had undergone several rounds of the QOL. pulmonary rehabilitation. Physical and mental changes Conclusion were evaluated in this patient after combined treatment We should pay much attention to care the with pulmonary rehabilitation and Waon therapy. psychosocial components of QOL as well as exercise As a result, physical change was not clear, but it was capacity and physical and mental subjective health suggested that there may be a good effect mentally. values in comprehensive cardiac rehabilitation programs. Key words: pulmonary rehabilitation, waon therapy, Key words: cardiac rehabilitation，SF-36v2，QOL， chronic respiratory failure exercise tolerance

15． Effects of Cardiac Rehabilitation on Physical 16． Determination of Meropenem in Human Plasma Capacity and Subjective Health Values in Patients by HPLC-UV 1） 1） with Acute Coronary Syndrome（ ACS） Tatsuro TAMATSUKURI , Masayuki OHBAYASHI , 1） 1） 1） 1） Ryu ARAI , Eiichi GESHI , Anri SASAKI , Noriko KOYAMA , 2） 2） 2） Shinji KOBA Ryo HIGUCHI , Kenichiro FUKUDA , 1） 2） 1） Showa University Shusuke MONMA , Yasuna KOBAYASHI , 2） 1） Graduate School of Health Sciences Kenji DOHI , Toshinori YAMAMOTO , 2） 1） Department of Medicine, Mari KOGO Division of Cardiology, 1） Division of Pharmacotherapeutics, Showa University School of Medicine Department of Clinical Pharmacy, Showa University School of Pharmacy Background 2） Department of Emergency and Although it is well-established that cardiac rehabilitation Critical Care Medicine, has beneficial effects on exercise tolerance, it remains Showa University School of Medicine to be determined how an elevated exercise capacity is 402 Proceedings of the 63rd General Meeting of the Showa University Society

Introduction faecium NCGM16 was isolated 59 days after the Meropenem （MEPM） is a broad-spectrum antibiotic transfer of a hospitalized patient from the United States used to treat serious infections such as sepsis. to Tokyo. VRE had not been isolated at the U.S. Augmented renal clearance （ARC） （＞ 130 ml/min/1.73 hospital, and the patient was not screened for VRE m2） is often observed in patients with sepsis, and upon admission to the hospital in Tokyo. Patients at MEPM clearance is reportedly increased in patients the latter hospital were subsequently screened for VRE with ARC. It would therefore be useful to determine to determine if an outbreak had occurred, and three the ideal drug dose in these patients using population other VRE carriers were detected. The VRE isolates pharmacokinetic analysis. The purpose of this study （NCGM17, 18, and 20） from these three carriers were was to establish an analytical method for determining identical to each other in drug susceptibility profiles, MEPM concentration by HPLC. patterns on pulsed-field gel electrophoresis, and multi- Methods locus sequence types, but differed from the NCGM16 A standard HPLC apparatus （Shimadzu） with a isolate from the original carrier. NCGM16 and 17 also Capcell Pak C18 UG120 （4.6 mm×150 mm） column had different types of Tn1546-like elements containing （SHISEIDO） was used throughout this study. The van A. These molecular epidemiology results indicate mobile phase was a mixture of 10 mM phosphate that an underlying outbreak of VRE occurred once the buffer （pH 7.4） and acetonitrile （90：10, v/v）, and transferred patient was in the Tokyo hospital, but that the ow rate was 1.0 ml/min. The MEPM peak was NCGM16 did not cause an outbreak in that hospital. detected at 300 nm. Restricted infection control measures were performed Results and discussion to contain the outbreak. This case report indicates that We used doripenem as an internal standard, and the active surveillance for VRE and molecular epidemiology retention time of MEPM exhibited at 4.7 min. High are useful in detecting VRE outbreaks. linearity was observed between 0.025 and 50 µg/ml （r2 Key words: vancomycin-resistant enterococci （VRE）, ＝ 0.9999）, and the limits of detection and quantitation VRE outbreak, active surveillance, Tn1546- were exhibited at 0.025 µg/ml （S/N ≧ 5） and 0.05 µg/ like element ml, respectively. Accuracy of 0.025 µg/ml and 0.05 µg/ ml demonstrated 21.6％ and -1.8％, respectively. The 18． Investigation of Streptococcus mutans（ S. mutans） coefficients of variation for those two concentrations in Caries Dentin Identified by a Visible Light- were 14％ and 4.8％, respectively. induced Fluorescence 1） 2） Conclusion Michi YAMADA , Takafumi ARIMOTO , 2） 2） We established a suitable HPLC method with an Hirobumi MORISAKI , Hirotaka KUWATA , 1） 1） internal standard for determining MEPM levels. Katsuhiko ISATSU , Tokuji HASEGAWA Key words: meropenem, HPLC, ARC 1） Department of Conservative Dentistry, Division of Comprehensive Dentistry, 17． Active Surveillance Revealing an Underlying Showa University School of Dentistry Nosocomial Outbreak of Vancomycin-Resistant 2） Department of Oral Microbiology Enterococcus faecium and Immunology,

Tomoki WATANABE, Satoko HANDA, Showa University School of Dentistry Yasuhisa KATO Department of Drug Information, Currently, clinical techniques based on the concept of Division of Drug Information Analytics, minimal intervention dentistry are recommended for the Showa University School of Pharmacy removal of caries-infected tooth substances during the treatment of dental caries. Conservative pulp therapy Japan is one of the countries with low prevalence which leaves infected dentin in the caries region does rates of vancomycin-resistant enterococci （VRE） not sterilize the cariogenic bacteria in the infected nosocomial infections. Vancomycin-resistant Enterococcus dentin. For this reason, to accurately remove the Proceedings of the 63rd General Meeting of the Showa University Society 403

infected dentin, re-entry of the caries region is necessary mass spectrometry microbial-identification system after a certain period of time. We have reported which uses matrix-assisted laser desorption ionization that a blue light, with wavelength of about 405 nm, time-of-ight. distinguishes between infected and sound dentin by their This study included 19 patients who underwent HSCT light-induced uorescence. In this study, the relationship for hematological malignancies in our hospital. All between the caries region distinguished by blue light, were treated in reverse isolation in a laminar airow- and the pathological structure of dental caries observed equipped room and received drugs to prevent bacterial, on thinly-sliced specimens, was investigated in extracted fungal, and herpes virus infection. OM was diagnosed human teeth with caries. In addition, immunostaining according to NCI-CTCAEv4.0 and the WHO scale. was employed for visualization of Streptococcus mutans Samples were obtained using swabs from bilateral buccal （S. mutans）, and real-time polymerase chain reaction mucosa, palate, and tongue. We evaluated the patients （RT-PCR） was used to determine the quantitative before the preparative regimen （1st）, day -1 before distribution of S. mutans. It was difficult to clearly HSCT （2nd）, and 7 days （3rd）, 14 days （4th）, and 30 distinguish a pioneer bacteria layer and a turbid layer days after HSCT（ 5th）. in the pathological specimens. In contrast, blue light The percentage of patients with high-grade OM showed a different fluorescence between the pioneer increased on days 7-14 and decreased at day 30. The bacteria layer and the turbid layer. Furthermore, a mean number of isolated species gradually decreased boundary between the two layers was observed in the from day -1 through to day 30. Many Streptococcus immunostaining study, and the amount of S. mutans in spp could be detected at the 1st or 2nd time point, but the pioneer bacteria layer was signi cantly higher than these species gradually decreased and were replaced in the turbid layer in the RT-PCR study （P ＜ 0.05 ; with coagulase-negative staphylococci. Before HSCT, Kruskal-Wallis test）. We concluded that this blue light Prevotella sp and Veillonella sp were detected in the can accurately detect caries-infected dentin. oral ora of many patients. Candida sp was detected Key words: light-induced fluorescence, S. mutans, after the preparative regimen. immunostaining, real-time PCR, caries- We found that the oral bacterial species changed infected dentin from Streptococcus sp, Prevotella sp, or Veillonella sp to coagulase-negative staphylococci or Candida sp 19． Detection of Microbial Substitution in the Oral after HSCT. Our results suggest that oral microbial Cavity of Patients Undergoing Hematopoietic substitution possibly underlies high-grade OM after HSCT. Stem Cell Transplantation Key words: oral mucositis, hematopoietic stem cell trans- 1） 1） Luna OSAKABE , Akemi UTSUMI , plantation, bacteria 2） 2） Bungo SAITO , Tsuyoshi NAKAMAKI , 1） Shouji HIRONAKA 1） Department of Special Needs Dentistry, Division of Hygiene and Oral Health, Showa University School of Dentistry 2） Departmen of Medicine, Division of Hematology, Showa University School of Medicine

Hematopoietic stem cell transplantation （HSCT）- induced oral mucositis （OM） is a major complication of preparative regimens. However, the precise bacterial substitution occurring in HSCT patients with OM remains unclear. We prospectively examined oral bacterial ora changes using VITEK MS, an automated 404 Proceedings of the 63rd General Meeting of the Showa University Society

20． Oral Cavity Function Management, Choking, and was then focused on management of the patient`s Aspiration Pneumonia Recurrence Prevention in dental hygiene and oral cavity function. a Neuropsychiatry Hospital Inpatient Eating bread was prohibited, owing to the associated 1） 2） Asako YAMAGUCHI , Toshiaki TSUNEOKA , high risk of aspiration and choking. The patient was 3） 4） Satoshi SUGISAWA , Aya SUZUKI , advised not to put too much food in his mouth when 1） 5） Kunie HIYAMA , Yuta UESUGI , eating. 5） 6） Shinji NOZUE , Mitsuhiko MATSUURA , However, one month later the patient was readmitted 7） 8） Yasubumi MARUOKA , Syouji HIRONAKA , to hospital having choked on his food ; 2 days later he 5） Koji TAKAHASHI was diagnosed with aspiration pneumonia. 1） Dental and Oral Surgery, After improvement in the patient’s mental state, he Showa University Karasuyama Hospital became receptive to following medical advice concerning 2） Department of Psychiatry, his problem, and a partial set of dentures was made for Showa University School of Medicine him. 3） Department of Hospital Pharmaceutics, Twenty-four months from this last choking episode, Showa University School of Pharmacy the patient has had no recurrence of choking or 4） Department of Notation, aspiration pneumonia. He is receiving medical Showa University Karasuyama Hospital treatment at the outpatient clinic. 5） Department of Special Needs Dentistry, Key words: o ra l c av i t y f u n c t i o n m a n a g e m e n t , Division of Oral Rehabilitation Medicine, team medical care, choking, nutritional Showa University School of Dentistry management, neuropsychiatric hospital 6） Dental and Oral Surgery, inpatient Showa University Fujigaoka Hospital 7） Department of Special Needs Dentistry, 21． Inhibitory Effect of Oxethazaine on CYP3A- Division of Community Based Comprehensive Dentistry, mediated Midazolam Metabolism in Rats 1） 1） Showa University School of Dentistry Hokuto NAMBA , Yuki NISHIMURA , 8） 1） 2） Department of Special Needs Dentistry, Mariko IWASE , Norimitsu KURATA , 1） 1） Division of Hygine and Oral Health, Takahito HIRAI , Katsuji OGUCHI , 1） Showa University School of Dentistry Yuji KIUCHI 1） Department of Pharmacology, Patients with mental disorders are reported to be at a Showa University School of Medicine high risk of choking. 2） Faculty of Arts and Sciences at Fujiyoshida, After providing provision of health education by Showa University the medical team to a patient, including oral cavity and nutritional management, self-regulated oral cavity Objective management was facilitated and the prevention of There have been few reports concerning drug- recurrence of choking and aspiration pneumonia drug interactions （DDI） with over-the-counter drugs. resulting from these steps is reported here. The current study was conducted to clarify DDI The patient was a 65-year-old man admitted to the through cytochrome P450 3A （CYP3A） inhibition by acute stage ward for treatment of bipolar emotional oxethazaine（ OXZ）, an antacid available as an over-the- disorder and an alcohol dependence syndrome. The counter drug. patient underwent a dental checkup to be assessed Methods for risk regarding food-related aspiration and choking. Midazolam （MDZ） was used as a probe drug for We diagnosed eating/swallowing dysfunction owing CYP3A activity. The inhibitory effect of OXZ on to masticatory disturbance caused by lowering of his MDZ 1’-hydroxylation activity was investigated in vitro consciousness levels, and mental state. Symptoms of using rat liver and intestinal microsomes. In an in extrapyramidal tract disorder were noted, and attention vivo study, rats were treated with a single oral dose of Proceedings of the 63rd General Meeting of the Showa University Society 405

OXZ （50 mg/kg） 15, 30, 60, 120 or 240 min before oral were collected for analysis following the treatments. MDZ administration （15 mg/kg）. The pharmacokinetic LF-TENS significantly increased plasma β-endorphin parameters of MDZ were compared with the water- levels compared to non-treated rats. In the second treated control group. experiment, formalin-induced inflammatory pain was Results and discussion induced immediately after treatment with LF-TENS The in vitro study showed that OXZ inhibited for 30 minutes, and the time spent licking, flinching MDZ 1’-hydroxylation activity in a concentration- and lifting the inamed hind paw was recorded for 60 dependent manner in the intestine as well as the liver. minutes. The frequency of pain-related behaviors was Pretreatment of rats with OXZ 120 min before MDZ increased by acute inammation; however, the signs of administration increased AUC 0-∞ of MDZ significantly distress were significantly reduced in LF-TENS-treated by 6 times compared to the control group without a rats. In addition, L4-5 spinal cords were removed and change in t1/2. In contrast, OXZ pretreatment 15, 30, processed for immunofluorescent staining to examine 60 or 240 min before MDZ administration did not whether or not the extracellular signal-regulated show any remarkable change in MDZ pharmacokinetic kinase （ERK） signaling pathway was involved in the parameters. These results suggest that OXZ increases analgesic effect of LF-TENS. We found the number serum MDZ concentration mainly by inhibition of of pERK（＋） cells in lamina Ⅰ-Ⅱ of the spinal cord intestinal CYP3A activity, however, this effect depends dorsal horn increased due to inflammation, and these on the dose interval. increases were signi cantly inhibited following LF-TENS. Conclusion These results suggest that the analgesic mechanism of OXZ was predicted to cause the DDI mediated by LF-TENS is mediated by inactivation of ERK via the CYP3A inhibition. It is necessary to consider the drug endogenous opioid system. interval when OXZ is co-administered with other drugs Key words: transcutaneous electrical nerve stimulation metabolized by CYP3A. （TENS）, antinociceptive effect, β-endorphin, Key words: over-the-counter drug, oxethazaine, drug-drug endogenous opioid, acute inammatory pain interaction, CYP3A 23．E liciting the Inammatory Regulation Mechanism 22． The Antinociceptive Effect of Transcutaneous Through the Innate Immune System by Melatonin 1） 2） Electrical Nerve Stimulation （TENS） via an Miki KADENA , Hitomi MATSUSHIMA , 3） 3） Opioid Mechanism in a Rat Model of Acute Hideo KATAOKA , Haruka FUKAMACHI , 3） 3） Inammation Takafumi ARIMOTO , Hirobumi MORISAKI , 1） 3） Yoshiyuki KOBAYASHI, Masataka SUNAGAWA, Takahiro FUNATSU , Hirotaka KUWATA 1） Hideshi IKEMOTO, Takeshi HIGUCHI, Department of Special Needs Dentistry, Tadashi HISAMITSU Division of Dentistry for Persons with Disabilities, Department of Physiology, Showa University School of Dentistry Showa University School of Medicine 2） Department of Pediatric Dentistry, Showa University School of Dentistry Transcutaneous electrical nerve stimulation （TENS） 3） Department of Oral Microbiology and Immunology, is a noninvasive physiotherapy method used to provide Showa University School of Dentistry pain relief by stimulating sensory nerves. Electrodes are attached directly to the skin, and electrical currents Various tissues in the body produce melatonin of varying frequency and intensity are delivered. The to elicit physiological functions such as circadian present study was performed to elucidate the analgesic rhythm. Past studies also implicated a role for effect and the mechanism of low-frequency （LF） TENS melatonin in inhibiting inflammatory induction by the on acute inflammatory pain. In the first experiment, immune system. Moreover, melatonin was recently LF （4 Hz） and high-frequency （HF, 100 Hz） TENS shown to suppress activation of a novel helper T were applied to intact rats, and blood samples cell subpopulation （Th17）, which are responsible for 406 Proceedings of the 63rd General Meeting of the Showa University Society causing inflammation in autoimmune diseases such as have attracted attention. We examined the protective multiple sclerosis, although the molecular mechanism effects of （-）-epigallocatechin gallate （EGCG） and （-）- underlying such immune suppression by melatonin is not epigallocatechin-3-（3”-O-methyl） gallate （EGCG3”Me） fully understood. This study sought to elucidate this on UV-induced cytotoxicity in cultured human corneal mechanism by characterizing the effect of melatonin on epithelial cells. cytokine regulation in macrophage cell lines induced by Methods lipopolysaccharide （LPS）, a cell-surface ligand for Toll- Cells were irradiated under UV lamps emitting 312 like receptors. nm radiation （4.94 mW/cm2, 296 mJ/cm2）. The UV We observed that melatonin treatment for 1 hour spectrum of the catechin was measured from 250 significantly reduced the LPS-dependent gene to 400 nm. After UV irradiation, membrane lipid induction of speci c cytokines including IL-6 and IFN- peroxide, tumor necrosis factor-α, reactive oxygen beta, despite the induction of TNF-alpha also being species generation, caspase-3, -8, and -9 activities, and suppressed. We also found by uorescence microscopic mitochondrial membrane potential were measured. analysis that the melatonin treatment decreased the Results macrophage ratio of F-actin to G-actin, which indicates Both EGCG and EGCG3”Me had an absorption the cellular responsiveness to LPS signaling. Finally, we maximum of approximately 275 nm. Membrane lipid found that melatonin treatment suppressed the activation peroxide, tumor necrosis factor-α and reactive oxygen of splenic innate immune cells and subsequently species production, and caspase-3, -8 and -9 activities suppressed Th17 activation in splenic lymphocytes, which were significantly increased after UV irradiation. require the innate immune induction via TLR-dependent However, these increases were signi cantly decreased by signaling. pretreatment with EGCG and EGCG3”Me, while there Taken together, these ndings suggest that melatonin was no change in mitochondrial membrane potential can regulate the innate immune response resulting after UV irradiation. in downstream effects on systemic immunological Conclusion homeostasis. Oxidative stress occurred in response to UV irra- Key words: melatonin, neuroimmunology, autoimmune diation and activated caspase-3 and -8 （without disease, cytokine regulation, innate immunity mitochondria） and also seemed to induce apoptosis. These findings suggest that EGCG and EGCG3”Me 24． Preventive Effects of Green Tea Catechins on absorb UV radiation and inhibit UV-induced membrane UV-induced Cytotoxicity in Human Corneal lipid hyperoxidation, and possibly suppress the apoptotic Epithelial Cells pathway through caspase-8. 1） 1） Akiko TOJU , Yuko UDAKA , Key words: cornea, catechin, UV, oxidative stress 1） 1） Mayumi TSUJI , Hideto OYAMADA , 1） 2） Akiko SASAKI , Junichiro KIZAKI , 25． Comprehensive Evaluation of Vehicles Difference 2） 1） Eiji TOMOYORI , Katsuji OGUCHI , and Strain Background Data on Results of Local 1） Yuji KIUCHI Lymph Node Assay 1） Department of Pharmacology, Showa University, Masamichi KAMINISHI, Takayuki ANZAI, School of Medicine Keizo SATO, Masaya FUJISHIRO, 2） Department of Ophthalmology, Showa University, Xiao-Pen LEE School of Medicine Department of Legal Medicine, Showa University School of Medicine Purpose The ocular surface is in direct contact with oxygen The local lymph node assay （LLNA）, which is and ultraviolet rays（ UV）, and exposed to strong photo- globally referred to as OECD Test Guideline 429, has oxidation stress, which can result in photokeratitis. In several advantages with regard to data objectivity and recent years, the antioxidant effects of tea catechins animal welfare. Advantages include the provision of Proceedings of the 63rd General Meeting of the Showa University Society 407 suitable quantitative data and the use of fewer animals. skills and risk management. This study aimed to clarify The purpose of this study was to comprehensively the educational effects of different learning tools on evaluate the effects of different mouse strains and orthodontic bonding practice and to investigate the vehicles on LLNA skin sensitization results. We usefulness of the patient robot. determined the background data in 6 mouse strains by Methods measuring 3H-methyl thymidine （3HTdR） incorporation Nine dentists participated in training that focused on as disintegrations per minute （dpm/LN level） and bonding orthodontic brackets to 5 teeth （31-35）. This also analyzed the effects of different vehicles on the involved using a mannequin and a patient robot, a local lymph node response. Under the conditions of lecture, and mutual training. Four items were analyzed this study, a large difference in the dpm/LN level was to determine the educational effectiveness of each noted between CBA/CaOlaHsd mice, which had the training tool : the examiner’s score, the bonding time, lowest background, and NMRI mice, which had the the bracket mounting position, and questionnaire results. highest background. This suggests that the Stimulation Results and discussion Index （SI） for reporting allergy activation may differ When training involved using the patient robot twice depending on the strain of animal tested. We also on the same day, the examiner’s score rose and the observed differences in the local lymph node response bonding time decreased. In addition, the examiner’s when CBA/CaHsdRcc （SPF） mice were exposed to 6 score did not decrease after a 14-day interval. In different vehicles : AOO, 70％ EtOH, DMF, BN, PG contrast, the examiner’s score decreased markedly when and DMSO. The dpm/LN level was lowest in the training using the patient robot was performed only 70％ EtOH group and highest in the DMSO group. once followed by a 14-day interval. Training using the When alpha-hexylcinnamaldehyde （HCA） was used patient robot led to signi cantly lower bracket heights as a sensitizer, EC3 values showed that HCA was a of 32 and 35 when compared to the bracket heights weak sensitizer when AOO and DMSO were used as obtained using a mannequin, which increased the vehicles but a moderate sensitizer when the other 4 deviation from the target value. The lecture and mutual vehicles were used. These results suggest that the dpm/ training had little immediate effects on orthodontic LN levels differ depending on the vehicle used and bonding practice. that the sensitization potency of a given sensitizer may Conclusion be classi ed in different categories when using different We demonstrated that using a patient robot to train vehicles. dentists is more difficult than using a mannequin. Key words: animal strain, local lymph node assay, Educational effects were influenced markedly when OECD test guideline, skin sensitization, feedback was received immediately after training and vehicle effect with iterative learning. We suggest that a patient robot is a useful educational tool for orthodontic bonding 26． The Utility of a Patient Robot in Orthodontic practice. Practice Key words: dental education, orthodontic practice,

Katsuyoshi FUTAKI, Tetsutaro YAMAGUCHI, patient robot, simulation Kousyu KATAYAMA, Ayumi KURIHARA, Wakana YANAGISAWA, Ayako YAGI, Mutsuko NAKAYAMA, Noriko MARUYAMA, Koutaro MAKI Department of Orthodontics, Showa University School of Dentistry

Objectives Simulation education that closely mimics actual practice is a valuable tool for teaching students clinical 408 Proceedings of the 63rd General Meeting of the Showa University Society

27． Effectiveness of Inter-professional Education for effectiveness of inter-professional education at our Medical Students university. 1, 2） 2） Megumi ENOKIDA , Eiichi GESHI , Key words: inter-professional education, competency, 3） Hisayoshi SUZUKI inter-professional work 1） Showa University Graduate School of Health Sciences 28． Consideration of a Patient’s Family Background 2） Department of Nursing, in Determining Organ Donation 1） 2） Showa University School of Nursing and Michihiro TSUBAKI , Eiichi GESHI , 1, 2） 2） Rehabilitation Sciences Megumi ENOKIDA , Satoko ABE 3） Department of Occupational Therapy, 1） Showa University Graduate School of Health Showa University School of Nursing and Sciences Rehabilitation Sciences 2） Department of Nursing, Showa University School of Nursing and Rehabilitation Sciences Purpose The purpose of this study was to clarify the Objective effectiveness of inter-professional education （IPE） for This study sought to clarify the decision-making medical students by conducting a qualitative study of support system related to organ donation for patients’ systematic IPE which has been introduced through all families at a tertiary emergency outpatient clinic. undergraduate years at Showa university. Methods Methods This study used survey forms concerning organ A qualitative study was conducted on the portfolio donation that were distributed to patients’ family of students’ inter-professional team medical practice members assembled at the tertiary emergency outpatient in hospital wards. This portfolio comprised the final clinic of a university hospital during the year from stage of IPE with the purpose of training students to October 2014. Family members completed the forms contribute to forth-coming inter-professional work. immediately after arrival at the clinic. This research Results and discussion also targeted nursing records of the same clinic Themes included : 1） Patient-centered team-based covering the same period. The survey results were medicine （students can understand the whole context analyzed to determine the subjects’ attitudes through for each patient and prioritise patient problems）, 2） statistical analysis. We also analyzed the nursing records Values/ethics for inter-professional practice （students qualitatively and inductively. can communicate with patients with respect for dignity Results and can evaluate the need for team medical services）, In total, 1,548 survey forms were collected. The 59 3） Roles/responsibilities （students can explain to other respondents （3.8％） answered positively to the question team members how the their roles and expertise can as to whether they recognized that the transported be utilized within the medical team and can proactively patient had indicated their wish to donate his/her seek understanding of all other areas）, 4） Inter- organs in his/her donor card, driver’s license, etc.. The professional communication （students can proactively rate of those who wanted an interview with the organ express their professional opinions after all team transport coordinator was significantly higher in the members have contributed to the team discussion）, and family members who recognized that the patient was 5） teams and teamwork （all team members understand willing to donate（ P＜0.001）. Regarding the qualitative viewpoints from other professionals to understand the consideration of nursing records, the circumstances under complete patient picture in order to develop the best which family members decided to donate the patient’s treatment plan）. organ had been influenced by “whether the patients Conclusion themselves had clearly indicated their wishes.” These five levels of achievement in medical Conclusion team education can be evaluated to determine the Family members’ decision-regarding the donation of a Proceedings of the 63rd General Meeting of the Showa University Society 409 patient’s organ is inuenced by whether they recognize 30． Clinical Characteristics of Adults with the patient’s wishes. Neurodevelopmental Disorders Admitted to Key words: transplantation, decision-making support, Emergency Psychiatric Wards

emergency medicine, family, organ donation Teppei MORITA, Marie OTA, Nobuyuki SAGA, Gousuke ARAI, 29． A Cohort Study of The Geographical Movement Daisuke IKUSE, Akira YOSHIZAWA, of Physicians after Japanese Postgraduate Clinical Masayuki TANI, Hiroki YAMADA, Training Programs Osamu TAKASHIO, Akira IWANAMI Takaya SHIMIZU, Tadahiro OHTSU, Department of Psychiatry, Hirotaka OCHIAI, Takako SHIRASAWA, Showa University School of Medicine Hinako NANRI, Akatsuki KOKAZE Department of Public Health, Objective Showa University School of Medicine Showa University Karasuyama Hospital is a mental health hospital with two emergency psychiatric wards. A new postgraduate clinical training system was This hospital has an outpatient department for adults initiated in 2004. This study aims to explore how with neurodevelopmental disorders, such as pervasive physicians are distributed across prefectures after developmental disorders （PDD） and attention deficit completing this training program. hyperactivity disorder （ADHD）. Individuals with The physicians targeted in this study are those who neurodevelopmental disorders often have comorbid graduated from medical universities in Japan in 2008 mental health disorders and show problematic behaviors, and went through the program for two years. All and short-term hospitalization is sometimes required. prefectures in Japan were grouped according to the The purpose of this study is to clarify the clinical number of medical universities in the prefecture. The characteristics and treatment outcome of adults with in-flow and out-flow of physicians between each neurodevelopmental disorders admitted to the emergency prefecture was calculated before and after the training psychiatric wards at Showa University Karasuyama program. The figures from each group are compared Hospital. to national averages. The data were obtained from the Methods Ministry of Health, Labour, and Welfare. We investigated the sociodemographic data, diagnosis, The results show that the rates of both in-flow medication status, and clinicaloutcomes of patients with and out-ow are 30％ at the national level. The rate neurodevelopmental disorders who were admitted to of out-flow from Tokyo is about 31％. There is no the emergency psychiatric wards between 1st of January, tatistically significant difference between this figure 2010 and 31st of December, 2013. Patientinformation and the national figure. However, when it comes to was gathered retrospectively from the medical records. the ratio of in-ow into Tokyo when compared to the Results national average, the ratio is 34％ which is statistically Fifty-eight patients with neurodevelopmental disorders signi cant （95％ CI 1.05-1.26）. Further analysis shows （mean age, 28.0 years SD, 9.6, 44 males and 14 that prefectures with only one medical university have a females） were admitted to the emergency psychiatric higher ratio of out-ow than the national average, and wards, including forty-nine patients with PDD （mean this rate is statistically signi cant（ 95％ CI 1.02-1.16）. age 27.2 years, 41 males and 8 females）, and nine This study demonstrates that following the completion patients with ADHD （mean age 32.4 years, 3 males of postgraduate clinical training programs, the outow of and 6 females）. The mean dose of chlorpromazine physicians from rural areas to Tokyo is above the national equivalent at discharge was 309.2 mg （SD 312.5）. The average, while outow from Tokyo is equal to the national mean duration of hospitalization in the acute wards was average. 54.7 days, and 84.5％ of patients returned home. Key words: post-graduate clinical training, geographical, Conclusion movement The results of this study show that emergency 410 Proceedings of the 63rd General Meeting of the Showa University Society hospi talization is available for the treatment of some nighttime-wearing of dentures, a lower frequency of adult patients with neurodevelopmental disorders. denture cleanser usage, and a coarser denture surface Key words: neurodevelopmental disorders, pervasive than the non-DC group（ P ＜ 0.05）. developmental disorders, attention deficit Discussion hyperactivity disorder, admit These results suggest the importance of proper denture usage/management for the prevention of DC 31． Effects of Denture Usage/Management on formation. Denture Calculus Formation Key words: denture calculus, denture usage, denture 1） 1） Keisuke MATSUMURA , Yuji SATO , management, surface roughness of denture 1） 1） Noboru KITAGAWA , Toshiharu SHICHITA , 1） 2） Daisuke KAWATA , Mariko ISHIKAWA 32． Factors Affecting the Maximum Torque Value of 1） Department of Geriatric Dentistry, Implant Drivers

Showa University School of Dentistry Tomoki NISHIUCHI, Yuji SATO, 2） Department of Special Needs Dentistry, Noboru KITAGAWA, Tokiko OSAWA, Division of Hygiene and Oral Health, Akio ISOBE Showa University School of Dentistry Department of Geriatric Dentistry, Showa University School of Dentistry Purpose A poor oral environment is caused by poor oral Purpose hygiene and inadequate denture management. Denture For xing a screw to the abutment and superstructure, plaque easily attaches to rough denture surfaces tightening the screw by hand is recommended before and becomes denture calculus （DC） with salivary using a torque wrench, as the torque force specified components. The rough surface of DC becomes the by implant manufacturers ranges from 15 to 35 starting point for tongue discomfort and breeding of N. Tightening an implant screw by hand allows for new bacteria, causing denture stomatitis. estimating the sensed torque force applied, preventing Self-care of dentures is dif cult because DC is rmly problems due to excessive or insuf cient torque. This attached to the denture surface. Denture plaque should study aimed to identify the factors that affect the be removed before calcification occurs. The purpose maximum torque value of implant drivers. of this study was to verify the effects of denture usage Methods and surface roughness of dentures on DC formation. Sixteen dentists （male and female） participated in Methods this study. Maximum torque values were measured with Fifty-three patients （average age, 79 years） who had a torque gauge and two kinds of hand drivers （Nobel used mandibular dentures, with at least an inter-canine Biocare Co. and Zimmer Co.）. The measurement denture base, for 3 months or more participated in the conditions were the rotation direction （clockwise or study. After cleaning with a sponge brush, the denture counterclockwise）, and whether gloves were worn or surface was stained with a plaque-staining solution. The not. The pain threshold and skin thickness at the participants were assigned to either the DC group （n thumb and forefinger were measured with a strain ＝ 18） or the non-DC group （n ＝ 35）. Denture usage gauge and an ultrasonic thickness gauge probe. The was recorded with a questionnaire. Surface roughness grip strength was measured with a hand dynamometer. of dentures was measured on 3 target areas after Results were analyzed with analysis of variance and t removal of DC. tests. The Chi-square test was used for differences in Results denture usage, and the Mann-Whitney U test was used Torque values were higher for males, clockwise for differences in surface roughness of dentures. rotation, and wearing of gloves （P ＜ 0.05）. The Results Zimmer Co. driver showed higher torque without The DC group had a higher frequency of gloves, than with gloves （P ＜ 0.05）. The maximum Proceedings of the 63rd General Meeting of the Showa University Society 411 torque value was correlated with grip strength and pain molar region significantly increased during the three threshold; however, skin thickness had no correlation months since placement compared to baseline, but with the torque value. showed no signi cant change at the implant-supported Discussion and conclusion prosthesis. These results suggest that sex, rotation direction, Conclusion wearing of gloves, driver shape, and pain threshold of These results suggest that the occlusal contact area the finger skin affect the maximum torque value of and occlusal load of the molar region, including that implant drivers. of the implant-supported prosthesis, increased with Key words: implant, torque, drivers, maximum increasing maximum clenching strength within three months after the implant-supported prosthesis placement. 33． Time-dependent Changes in Occlusal Status with Key words: occlusal load, occlusal contact area, implant, an Implant-supported Prosthesis clenching strength

Mayumi TERAZAWA, Yuji SATO, Noboru KITAGAWA, Tokiko OSAWA, 34． Predicting the Outcomes of Dental Implant Yoshiki IMAMURA, Yukihiko OKADA Treatment Using Four Sub-Domains of the Oral Department of Geriatric Dentistry, Health Impact Pro le

Showa University School of Dentistry Kayo MUKAWA, Daisuke HIGUCHI, Takashi MATSUMOTO, Maoko HARA, Purpose Kazuyoshi BABA Overload of the implant-supported prosthesis regarded Department of Prosthodontics, as important, because complications with implant Showa University School of Dentistry treatment usually arise after a year since implant- supported prosthesis placement. It hasn’t been clear Objective what kind of time-dependent change does occur Oral Health Impact Profile （OHIP） is one of the since implant-supported prosthesis placement. This most popular questionnaires to evaluate oral health- study aimed to clarify the time-dependent changes in related quality of life （OHRQoL）. We recently occlusal status of an implant-supported prosthesis at the reported that the OHIP contains four sub-domains, mandibular first molar, from baseline to three months comprising “Oral Function“, “Orofacial Pain”, “Orofacial after implant-supported prosthesis placement. Appearance”, and “Psychosocial Impact”, and that these Methods sub-domains could serve as a framework to understand The subjects comprised six patients with no and measure the impact of oral conditions. The aim of missing teeth other than the implant, and an implant- this study was to explore the factors inuencing dental supported prosthesis on the mandibular rst molar. implant treatment outcomes as evaluated by the OHIP. Electromyograms were obtained during maximum Methods clenching in the intercuspal position and recorded as Subjects were recruited at the Department of Pros- 100％ of the maximum voluntary contraction （MVC）. thodontics and Implant Center at Showa University Next, occlusal load and contact area were recorded between April 2008 and August 2015. In total, 152 three times each at MVC clenching levels of 40, 60, 80, subjects with a mean age of 57.9 ± 11.6 years par- and 100％ using a pressure-sensitive sheet and bite-force ticipated in this study after giving informed consent. measurement system. Occlusal contact area was also OHIP scores were collected before and after treatment. recorded once at the MVC clenching levels of 20, 40, Stepwise multiple regression analyses and the paired and 60％ by an occlusal contact-checking material and t-test were used for statistical analysis （SPSS 22.0, P ＜ bite-area measurement system. The results at baseline 0.05）. and at three months after placement were compared. Results and conclusion Results The average OHIP summary score as well as each of The occlusal contact area and occlusal load on the the four sub-domain scores were signi cantly improved 412 Proceedings of the 63rd General Meeting of the Showa University Society after treatment （P ＜ 0.01）. Patients with a large was accompanied by the meningeal vein. number of missing teeth showed a significantly larger Conclusion improvement in the OHIP summary score （P ＜ 0.01）. The bony canal is located around the pterion and Patients with implant embedded in both jaws and no is formed during bone growth. The MMA is covered occlusal support exhibited significant improvements in with collagen brous tissues and accompanied by small all sub-domain scores （P ＜ 0.05）. Our results suggest arterial branches and the meningeal vein inside the that the dental implant is effective treatment to improve bony canal. It is possible to safely expose and preserve OHRQoL, and that these pre-treatment factors could the MMA during craniotomy with careful drilling. predict the treatment outcome of the dental implant. Key words: microsurgical anatomy, meningeal arteries, Key words: dental implants, oral health-related quality of bony canal, craniotomy life, treatment outcomes 36． IRF6 Variants are Associated with Nasolabial 35． Intracranial Bony Canal of the Middle Meningeal Morphology Artery : Morphological and Histological Analysis Daisuke TOMITA, Tetsutaro YAMAGUCHI, 1, 2） 1） Michio FUJIMOTO , Naruhito OTSUKA , Takatoshi NAKAWAKI, Yu HIKITA, 1） 1） Hiromitsu EZURE , Ryoichi MORI , Shugo HAGA, Masahiro TAKAHASHI, 1） 1） Hiroshi MORIYAMA , Yuriko INOUE Koutaro MAKI 1） Department of Anatomy, Department of Orthodontics, Showa University School of Medicine School of Dentistry, Showa University 2） Department of Neurosurgery, Shin-yurigaoka General Hospital Objective The interferon regulatory factor 6（ IRF6） gene is one Objective of the most conspicuous candidate risk genes for non- Preserving the middle meningeal artery （MMA） syndromic cleft lip with or without cleft palate. Variants is important during neurological surgery ; however, if of IRF6 are also suggested to affect normal craniofacial it passes through a bony canal this artery must be variation with respect to face surface shape. The exposed by drilling around the pterion. We investigated objective of this study was to con rm the relationship the morphological and histological features of the bony between IRF6 and sagittal nasolabial morphology in canal to improve surgical results in such cases. healthy Japanese and Korean subjects and to identify Materials and methods whether soft or hard tissues are responsible for any Fifty adult dry skulls were investigated. The proximal association. and distal points of the bony canal were plotted on the Materials and methods surfaces of the skull to show the canal’s course, while Genomic DNA was obtained from 215 Japanese its length and the distance from the orbital rim to the and 226 Korean individuals. Five IRF6 SNPs （single bony canal were measured. Additionally, 28 cadaveric nucleotide polymorphisms）, rs17389541, rs642961, heads were dissected and examined histologically. rs2013162, rs2235371, and rs7802, were genotyped. Results These SNPs were tested for association with craniofacial Sixty-three bony canals were found in 43 skulls. The measurements obtained from lateral cephalograms using mean length of bony canals was 9.2 mm, and the mean multiple regression analysis. distance from the orbital rim was 24.0 mm. The bony Results canal ran mainly from the sphenoid bone （69.8％） to We observed signi cant associations of the rs2013162 the parietal bone （73.0％）. On histological evaluation, and rs2235371 SNPs with the distance from a facial both sides of the meningeal grooves gradually closed bone plane （NA plane） to the lateral alare inferius the distance, and nally formed the bony canal. The （NA-LAi） and the subnasale （NA-Sn） in the sagittal MMA inside the bony canal was enveloped with plane. collagen brous tissues, divided into small branches, and Proceedings of the 63rd General Meeting of the Showa University Society 413

Conclusion specific and strong emotions associated with the past Our results indicate that IRF6 variants have an along with retrieval of the vividness of spatial and important role in the normal range of variation in episodic memories, and these feelings might be linked to nasolabial soft-tissue morphology. retrosplenial cortex and precuneus activation. Key words: cephalometry, cleft lip, cleft palate, interferon Key words: autobiographical memory, fMRI, precuneus, regulatory factor 6 gene retrosplenial cortex

37． Odor-Induced Autographical Memory Associated 38． The New Concept Spinal Sagittal Alignment of with Activity in the Posterior Parts of the Brain the Patients with Hip Osteoarthritis

and the Limbic Olfactory Areas Kazumasa WATANABE, Koji KANZAKI, 1） 1） Keiko WATANABE , Yuri MASAOKA , Junichi OCHIAI, Tomohiro YASUDA, 2） 1） Nobuyoshi KOIWA , Akira YOSHIKAWA , Takayuki NAKAJIMA 3） 3） Mitsuru KAWAMURA , Kenjirou ONO , Department of Orthopedic Surgery, 1） Masahiko IZUMIZAKI Showa University Fujigaoka Hospital 1） Department of Physiology, Showa University School of Medicine Purpose 2） Department of Health and Science, This study evaluated sagittal alignment of the whole University of Human Arts and Sciences spine in patients with hip-osteoarthritis （OA） treated 3） Department of Medicine, surgically with total hip arthroplasty（ THA）. Division of Neurology, Materials and methods Showa University School of Medicine The study analyzed 120 consecutive patients with hip- OA treated surgically with THA, comprising 6 men Memories induced by odors enable individuals to and 114 women, with a mean age of 60.4 years. Of mentally travel back into their personal past. In this these patients, 81 had hip-OA with dysplasia, 25 had no study, we used functional magnetic resonance imaging dysplasia and 14 had reasons for trauma or the others. （fMRI） to analyze brain areas related to odor- All patients were evaluated by lateral-view whole-spine induced autobiographical memory （AM） and emotions X-ray in standing position. The Jackson method was in healthy subjects. The three different odor stimuli used to statistically evaluate sagittal alignment, pelvic used, tatami, baby powder, and osmanthus, all elicited angle （PA）, sacropelvic translation （PT）, lordosis angle a specific, pleasant, and autobiographical memory. including hip joints PR-T12, and other parameters from The fMRI study was divided into 2 sessions/runs: （i） the X-ray images. periods of AM odor interleaved with unscented air, Results and （ii） periods of control odor （rose） interleaved with The group of hip-OA patients with dysplasia had unscented air. Each session comprised 5 unscented an average PA of 19.3 degrees, lordosis angle of 51.7 and 5 scented blocks, of 30 s each. Subjects were degrees, distance B of 20.4 mm, and PR-T12 of 81.4 instructed to breathe normally through a nose mask for degrees. On the other hand, the cases without dysplasia delivering odors and for measurement of respiratory had an average PA of 23.1 degrees, lordosis angle of flow. The AM odors increased tidal volume and 42.5 degrees, distance B of 34.5 mm, and PR-T12 of decreased respiratory frequency, with activation of the 73.0 degrees. olfactory limbic areas including amygdala, hippocampus, Discussion and orbitofrontal cortex. These odors also activated The hip-OA cases studied herein overall showed posterior parts of the brain including the retrosplenial rotation of the pelvis covering the hip joints, and cortex and medial areas of the superior parietal cortex increased lumbar lordosis in the cases with dysplasia. of the precuneus ; such areas have reported roles in Some of the patients without dysplasia showed episodic memory retrieval and visuospatial processing, decreased lordosis of the lumbar spine with progression respectively. In conclusion, the AM odors induced of degenerative changes and the pelvis rotated 414 Proceedings of the 63rd General Meeting of the Showa University Society

poste riorly, together with a decreased covering of the survival. hips decreased and progressive OA change. Key words: RANKL, denosumab, pregnancy, osteoporo- Conclusion sis, bone tumor The etiology of hip OA is different between cases with dysplasia and cases without dysplasia. 40． Localization and Function of the Nectin Family Key words: hip-spine syndrome, spine sagittal alignment, of Intercellular Adhesion Molecules in Mouse hip osteoarthritis, total hip arthroplasty Ameloblasts 1） 2） Tsubasa KAWASHIMA , Jiro TAKITO , 1） 1） 39． Effects of anti-RANKL Antibody on Pregnant Masashi SATO , Mitsuko INOUE , 1, 3） 2） Mice Takashi MIYAZAKI , Masanori NAKAMURA 1, 2） 3） 1） Nobuaki OKAMATSU , Nobuhiro SAKAI , Department of Pediatric Dentistry, 3） 3） Takako NEGISHI-KOGA , Akiko KARAKAWA , Showa University School of Dentistry 3） 2） 2） Masamichi TAKAMI , Katsunori INAGAKI , Department of Oral Anatomy and Developmental Biology, 1） 1） Yuji KIUCHI , Katsuji OGUCHI Showa University School of Dentistry 1） Department of Pharmacology, 3）Department of Conservative Dentistry, Showa University School of Medicine Division of Biomaterials and Engineering, 2） Department of Orthopaedic Surgery, Showa University School of Dentistry Showa University School of Medicine 3） Department of Pharmacology, Mutations in nectin-1 are associated with cleft lip/ Showa University School of Dentistry palate-ectodermal dysplasia （CLPED1）, although nectin-1 null mice exhibit milder defects in teeth. Denosumab, a fully human monoclonal antibody Nectins are a family of immunoglobulin-like cell- （Ab） that neutralizes receptor activator of nuclear cell adhesion molecules in epithelia, comprising four factor- κ B ligand （RANKL） and blocks bone members, nectin-1 to -4. To examine the roles of resorption by osteoclasts, is currently administered nectins in amelogenesis, we localized these proteins in to patients with osteoporosis and bone metastasis. mouse mandibular incisors by immunohistochemistry. Administration of anti-RANKL Ab during pregnancy Confocal microscopy revealed that nectin-4 and nectin-2 is contraindicated, although the exact detrimental localized mainly at the distal adherens junctions of effects on mother and fetus are not understood. We the secretory stage ameloblasts, whereas nectin-1 and investigated the effects of an anti-RANKL Ab in mouse nectin-3 were distributed at the proximal adherens mothers and their newborns. Mothers injected with junctions of maturation stage ameloblasts, the stratum the anti-RANKL Ab had 24.7％ greater bone mass intermedium and papillary layer. Real-time RT-PCR than the control group, while newborn mice exposed analyses showed that nectin-1 and nectin-3 mRNAs to the Ab in utero died within 48 hours after birth. were expressed 15-fold higher than that of nectin-2 in None of the newborns had milk in their stomachs, the enamel organs from mouse mandibular incisors. suggesting that they died due to a nursing defect We next examined the phenotypes of nectin-2 null present in their mothers. Furthermore, histological mice. There was no difference in bone density of the analysis revealed abnormal mammary gland morphology mandible, incisor and molar shape, or pigmentation in the anti-RANKL Ab-injected mothers. On the of the mandibular incisor surface between the wild- other hand, nursing by healthy surrogate mothers type and the nectin-2 null mice at 1 years of age. The rescued only 33％ of neonates exposed to the anti- mandibles of 3- and 8-week-old nectin-2 null mice RANKL Ab, suggesting that neonatal lethality was due, showed normal histology. Organ culture using the at least in part, to an intrinsic defect in the newborns. tooth organ from E16 nectin-2 null embryo con rmed Our findings show that anti-RANKL antibody admin- that ameloblast development and the formation of istration during pregnancy causes an undesirable increase dentin and enamel proceeded normally in the absence in bone mass and has harmful effects on newborn of nectin-2. The results suggested that all nectins are Proceedings of the 63rd General Meeting of the Showa University Society 415 differentially expressed in the mouse incisor. As such, children because the MRFT score increases with age. any teeth defects in the nectin-2 null mice might be The MRFT score is related to eating behavior; hence, compensated by the heterophilic interactions of other children with low MRFT scores should be supported nectins. appropriately. MRFT was not correlated with occlusal Key words: ameloblast, cell-cell adhesion, mouse teeth, force or the thickness and length of the masseter nectin muscle; therefore, it is necessary to examine the oral dexterity, using MRFT, when evaluating the oral 41． Effectiveness of a Mouth Rinsing Function Test function of children. for Evaluating the Oral Function of Children Key words: oral function, mouth rinsing, eating behavior, 1） 1） Ayano OGAWA , Akiko ISHIZAKI , occlusal force, masseter muscle 1） 1, 2） Takuya ASAMI , Hyosong KWON , 1） 1, 3） Kanako FUJII , Akinobu TANAKA , 42． Prediction of Aspiration by Perceptual Evaluation 1） Shouji HIRONAKA of Wetness of Pre-swallow Voice Before 1） Department of Special Needs Dentistry, Videouoroscopic Examination

Division of Hygiene and Oral Health, Koji ONUMA, Koji TAKAHASHI, Showa University School of Dentistry Kaoru YOKOYAMA, Ken YUASA, 2） K Dental Clinic Shinji NOZUE 3） Tanaka Dental Clinic Department of Special Needs Dentistry, Division of Oral Rehabilitation Medicine, Aim Showa University School of Dentistry There has been an increase in consultations related Purpose to eating and oral function of children, such as not The aim of this study was to investigate the chewing food properly and swallow without chewing; relationship between perceptual evaluations of however, there have been few studies about oral the wetness of pre-swallow voice and findings of function evaluation. We have devised a mouth rinsing videouoroscopic swallowing studies（ VFSS）. function test （MRFT） to evaluate the oral function of Methods children by grading mouth rinsing function into five Voice samples were obtained from 45 patients with stages. We aimed to investigate the effectiveness of head and neck cancer. Pre-swallow utterances of the MRFT for evaluating the oral function of children and date were recorded immediately before VFSS. During to investigate factors relating to the MRFT scores. VFSS, subjects were asked to swallow 3 ml of a jelly- Methods like radiopaque test food. The VFSS findings were The participants were 182 children （age 3-6 years; evaluated using the penetration aspiration （PA） scale. 98 boys and 84 girls） attending nursery school, who The 45 voice samples were randomized and presented underwent an oral examination and evaluation of to 16 examiners, who undertook perceptual evaluation MRFT and occlusal force. Data on growth history and of the wetness of the voice samples. To evaluate eating behavior were collected from parents through a intrarater reliability, examiners re-evaluated voice samples questionnaire. 2 weeks after the rst evaluation. As acoustic analyses, Results variations in the fundamental frequency and amplitude The MRFT score signi cantly correlated with age and （jitter and shimmer） of voice samples were measured. if breastfeeding or bottle-feeding was stopped earlier. Relationships between the wetness of voice samples and Children whose parents worried about their eating VFSS ndings were analyzed. habits tended to have lower MRFT scores. There was Results and conclusion no significant correlation with occlusal force or the High inter- and intrarater reliabilities were verified thickness and length of the masseter. for perceptual evaluation of wetness of pre-swallow Conclusions voice. The wet voice group tended to be judged as MRFT is effective for evaluating the oral function of having aspiration or penetration in VFSS. The jitter 416 Proceedings of the 63rd General Meeting of the Showa University Society and shimmer of voice samples were signi cantly higher Conclusion in the dysphagic than non-dysphagic group. Hoarseness This study has shown that it is dif cult to estimate and hypernasality after cancer treatment may have an elasticity using the thickness of denture-supporting tissue. effect on the evaluation of wetness of pre-swallow voice, It has demonstrated that it is necessary to optimize and further investigations are needed. the elasticity of all palatal parts using FEA, and has Key words: wetness of voice, perceptual evaluation, established a method of measuring elasticity. acoustic analysis, videofluoroscopic swallow- Key words: FEA, denture support mucosa, elastic ing study modulus

43． Establishment of the Modulus Measuring Method 44． Signal Intensity of Cortical Bone and Tempo- in Denture Supporting Tissue Using an Intraoral romandibular Joint Discs on Magnetic Resonance Simultaneous Measuring System and FEA Images 1） 2） Naoya TAKAMATSU, Yuji SATO, Mamiko FUJIKURA , Kazuyuki ARAKI , 1） Noboru KITAGAWA, Osamu SHIMODAIRA, Kenji MISHIMA 1） Takamasa OGAWA, Akio ISOBE, Division of Pathology, Yuko KAMISAWA, Satomi TANAKA Department of Oral Diagnostic Sciences, Department of Geriatric Dentistry, Showa University School of Dentistry Showa University School of Dentistry 2）Department of Oral Diagnostic Sciences, Division of Radiology, Purpose Showa University School of Dentistry In this study, we examined a three-dimensional finite element analysis （FEA） method for measuring Objective and estimating elasticity using thickness and load data The purpose of this study was to clarify the validity collected from elderly edentulous patients complaining of measuring signal intensities of cortical bone （CB） of pressure-related pain. and temporomandibular joint （TMJ） discs on clinical Methods magnetic resonance（ MR） images. Subjects were 17 patients wearing complete maxillary Methods dentures （eight men and nine women; average age, 78.4 Two investigations were performed. In the rst, MR years）, and experiments were carried out at three sites images of 13 TMJs of volunteers were obtained using on each patient’s palate: the median part of the palate, a multi spin-echo sequence. Echo time （TE） was the lateral part of the first molar, and the midpoint changed from 10 to 200 ms in steps of 10 ms. The between these two. We tested elasticity as measured signal intensities of CB, and the anterior （AD） and in a previous report （“measured elasticity”） and that posterior （PD） bands of the TMJ disc were measured, measured using FEA （“estimated elasticity”） by two- and their attenuation patterns were compared. In the way ANOVA, and determined the Pearson’s correlation second investigation, clinical MR images of 30 TMJs coef cient. We also determined the Pearson’s correla- of patients with suspected temporomandibular disorders tion coef cient for thickness （mm）, measured elasticity, were selected. Proton density-weighted images（ PDWIs） and estimated elasticity （MPa） at different experimental and T2-weighted images （T2WIs） were obtained at TE sites of 14 and 85 ms, respectively, using a double-echo fast Results spin-echo sequence. CB, AD and PD signal intensities Although individual differences were large, the were measured and compared with that of the external estimated elastic modulus （0.39 ± 0.22 MPa） at all sites acoustic foramen（ air） using a Bonferroni test. was signi cantly lower than the measured values （1.14 Results ± 0.65 MPa） （P ＜ 0.05）. Moreover, no correlation was AD and PD showed nearly identical signal intensity found between thickness and the elastic modulus of the attenuation patterns. AD and PD signal intensities were denture-supporting mucosa at any of the three sites. higher than CB at TEs shorter than 20 ms; however, Proceedings of the 63rd General Meeting of the Showa University Society 417

at TEs longer than 20 ms, CB showed higher signal impressions were fewer than those observed with the intensity than AD and PD. Clinical PDWIs and T2WIs silicone impressions. Statistical analysis confirmed a showed similar results. The signal intensities of CB, signi cantly better average inter-operator reproducibility AD and PD were signi cantly higher than the external using the digital impression technique （0.014 ± 0.02 mm） acoustic foramen（ air） on both PDWI and T2WI. compared to the conventional impression technique Conclusion （0.023 ± 0.01 mm, P ＜ 0.05）. CB and TMJ discs show characteristic signal Conclusion intensities, suggesting that signal intensity measurement These in vivo results suggest that the inter-operator of these structures is valid. reproducibility of a digital impression technique may be Key words: MRI, signal intensity, cortical bone, TMJ disc better than that of a conventional impression technique, and is independent of the clinical experience of the 45． In Vivo Evaluation of Inter-operator Reproduc- operator. ibility of Digital Impression Techniques Key words: digital impression, intraoral scanner, repro-

Emi KAMIMURA, Shinpei TANAKA, ducibility, in vivo study Masayuki TAKABA, Keita TACHI, Kazuyoshi BABA 46． The Effects of Relief of Palatal Plates on Sup- Department of Prosthodontics, porting Ability

Showa University School of Dentistry Satomi TANAKA, Yuji SATO, Noboru KITAGAWA, Osamu SHIMODAIRA, Purpose Akio ISOBE, Yuko KAMISAWA, The aim of this study was to evaluate and compare Naoya TAKAMATSU, Tomoka OMORI the inter-operator reproducibility of three-dimensional Department of Geriatric Dentistry, （3D） images of teeth captured by a digital impression Showa University School of Dentistry technique and a conventional impression technique in vivo. Purpose Materials and methods The purpose of this study was to clarify the effects A digital impression of the mandibular molars of of palatal midline relief on supporting ability in dentate the study participants was made by two operators with subjects. A measurement system in the form of palatal different levels of clinical experience, 3 or 16 years, plates that can simultaneously measure clenching force using an intra-oral scanner. A silicone impression also and subsidence of the palatal mucosa was developed. was made by the same operators using the double- Methods mix impression technique. Stereolithography （STL） Fifteen dentate subjects consented to participate in data were directly exported from the intra-oral scanner, the study after receiving an explanation of the goals while STL data of a plaster model made from the of the study. None of the subjects had significant silicone impression were captured by a 3D-laboratory palatal torus and abnormalities of the palatal mucosa. scanner. The STL datasets recorded by the two “Pseudo-palatal plates” were inserted in all subjects different operators were compared using 3D-evaluation to mediate clenching force. “Anterior splints” were software and superimposed using the best-fit-algorithm inserted as a reference for measuring subsidence of the method （least-squares method, PolyWorks, InnovMetric upper jaw. In the lower jaw, “Pressurizing splints” were Software） for each impression technique. Inter- inserted to apply clenching force to the palatal plates. operator reproducibility was evaluated by the average Three types of palatal plates were used: no relief, 0.23- discrepancies of corresponding 3D data, and compared mm relief, and 0.46-mm relief. Subjects were instructed between the two techniques（ paired t test, P ＜ 0.05）. to clench until pain occurred, and the clenching Results force and palatal mucosa subsidence were measured The visual inspection of superimposed datasets simultaneously with load cells and ultrasonic thickness revealed that discrepancies between the digital gauges, respectively. 418 Proceedings of the 63rd General Meeting of the Showa University Society

Results plate with upper and lower positing surfaces to advance Both clenching force and subsidence of the palatal the mandible to the forward position. The plate is mucosa at the time of pain were higher under 0.46-mm attached to a mechanical slider to measure the force and 0.23-mm relief conditions compared with no relief applied using a digital strain gauge weight scale. At the （two-way ANOVA, P ＜ 0.05）. However, subsidence of same time, positional information, judgment of arrival the palate mucosa and clenching force decreased with at the forward position of the mandible, and elapsed increasing relief in some patients. time are acquired electronically. All measurements Conclusion were acquired while patients were in a sitting or supine Relief at the median palatal plate is effective in position. improving the supporting ability of the palatal region. Results and conclusion However, the appropriate range and amount of relief The amount of mandibular traction force varied differs between subjects because of differences in palate depending on the morphology of the mandible. form and palatal mucosal properties. Key words: functional appliance, class Ⅱ malocclusion Key words: c lenching force, subsidence of palatal mucosa, relief, supporting ability 48． Effects of the Residual Ridge Form and Denture Form of Mandibular Complete Dentures on 47． Discussion about Mechanical Load of Functional Retention Force Appliances Masae ISHIHARA, Yuji SATO, 1） 2） Aya SHIMAZAKI , Hitoshi KIMURA , Noboru KITAGAWA, Momoe NAKATSU, 2） 1） Norio INOU , Kotaro MAKI Kana TAKEDA, Takuya KAKUDA, 1） Department of Orthodontics, Mari TAKAYAMA, Kensuke TSUBAKIDA Showa University School of Dentistry Department of Geriatric Dentistry, 2） Departmet of Mechanical Engineering, Showa University School of Dentistry School of Engineering, Tokyo Institute of Technology Purpose A method to evaluate the retention force of Objective mandibular complete dentures has not been established. The Andresen Activator is a functional appliance Determining the appropriate size of the mouth opening indicated for the treatment of skeletal malocclusion is necessary for measurement of retention force. The caused by undergrowth of the mandible. Nowadays aim of the present study was to determine the size of functional appliances are widely used in clinical practice. the mouth opening to measure retention forces and However, although many studies have reported on to clarify the effects of residual ridge forms on the the various effects of the Activator, the mechanism retention forces of dentures. as to how it improves skeletal malocclusion remains Methods unclear. The objective of this study was to examine Thirty-seven patients with an edentulous mandible the mechanical load delivered to the mandible by the participated in the study. The edges of the central functional appliance. incisors were loaded in a direction 45° downward to the Subjects and methods occlusal plane. Mouth opening was specified at 1, 2, The study subjects were 10 patients （five male, or 3 cm and was measured four times each. Retention five female） diagnosed as having skeletal Class Ⅱ forces were compared to the form of the molar residual malocclusion due to mandibular undergrowth and ridge and the relative position of the anterior residual treated by functional appliances. The force required ridge. to displace the mandible from the resting to forward Results position was defined as the mandibular traction force. Retention force decreased with larger mouth opening This force was measured using a new device developed sizes （P ＜ 0.05）. The smallest coef cient of variation especially for that purpose. This device consists of a was associated with a mouth opening of 1 cm. As Proceedings of the 63rd General Meeting of the Showa University Society 419 the ratio of the distance of the central incisor to the parts to neighboring teeth. Material properties were anterior residual ridge and the distance of the central assigned to teeth, attachments, the aligner, and PDL. incisor to the posterior denture border increased, The orthodontic force and the created moment under retention force decreased （P ＜ 0.01）. No correlation stable conditions were calculated. was found between the shape of the posterior molar The computational results showed that the attachment region of the residual ridge and retention force. changed the effect of the orthodontic force depending However, the retention force decreased with a decrease on the attachment conditions on each tooth. in the height of the posterior molar area（ P ＜ 0.01）. In conclusion, the presence of attachments contributes Conclusion to the regulation of the effectiveness of the applied The results suggest that mouth opening be regulated orthodontic force. to 1 cm for appropriate measurement of mandibular Key words: orthodontics, aligner, attachment, finite denture retention. In addition, the retention force of element method, mouthpiece type of ortho- dentures is affected by the relative position of the dontic appliance anterior residual ridge. Key words: retention force, mandibular complete denture 50． Evaluation of the Fit Comparison of Cerec Bluecam and Omnicam 1） 2） 49． Three-dimensional Finite Element Analysis Meguru YAMAMOTO , Yu KATAOKA , 1） 2） of the Mechanical Effects of Attachments in Atsufumi MANABE , Takashi MIYAZAKI Mouthpiece-type Orthodontic Appliances 1） Department of Conservative Dentistry, 1） 1） Mariko GOTO , Wakana YANAGISAWA , Division of Aesthetic Dentistry and Clinical Cariology, 2） 2） Hitoshi KIMURA , Norio INOU , Showa University School of Dentistry 1） 2） Kotaro MAKI Department of Conservative Dentistry, 1） Department of Orthodontics, Division of Biomaterials and Engineering, Showa University School of Dentistry Showa University of School of Dentistry 2） Department of Mechanical Engineering School of Engineering, Purpose Tokyo Institute of Technology Recent increases in esthetic demand have led to a The use of thermoplastic aligner appliances, such rapid rise in the number of metal-free restorations. as InvisalignⓇ （Align Technology, Santa Clara, CA, Standardization of the outer layers of dental prostheses USA）, is becoming widespread. The aligner treatment prepared with a dental CAD/CAM system is also occasionally causes unexpected tooth movement, called in progress, and many studies on digital impression a “bowing effect”. In extraction cases, molars tend acquisition methods have been reported. However, few to tip towards the extraction space. To improve the studies have investigated digital impressions for internal predictability of orthodontic movement, the use of cavities. This study compared two digital impression supplementary attachments is recommended. However, acquisition systems for internal cavities. the effects of supplementary attachments have not yet Materials and methods been elucidated. In the present study, we evaluated A system that acquires single images （the BL group : the mechanical effects of the attachments using finite Cerec BluCam Ver. 4.0） and a system that acquires full- element analysis. color video（ the OM group : Cerec OmniCam, Ver. 4.2）. To perform computational analysis, a two-tooth nite For measurement, silicone impressions were prepared element model （canine and second premolar, including from an ISO-standard metal mold, and CEREC periodontal ligaments ［PDL］） was constructed. Vertical Stone BC and New Fuji Rock IMP were used to rectangular attachments （4×1×1 mm L×W×H） were make working models in the BL and the OM groups, added to the center of the crown labial surfaces. The respectively. Then, individual inlays were designed in a aligner was made using a shell element based on tooth conventional manner using designated software, and all shape. The two ends of the aligner had connecting restorations were prepared using CEREC inLab MCXL. 420 Proceedings of the 63rd General Meeting of the Showa University Society

These were assembled with the corresponding working models used for measurement, and the level of t was examined by three-dimensional analysis based on micro- CT imaging. Results Measurements calculated three-dimensionally showed unique characteristics at sites other than those with preset values in the cement space, albeit with no signi cant differences between the two groups. Conclusion Both digital impression acquisition methods gave a good level of clinical fitting. However, there were certain levels of differences in processing accuracy. In the future, we plan to compare the two methods using impressions made directly in the oral cavity. Key words: CAD/CAM, internal cavity, µ-CT