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 香川共同リポジトリは、香川県内で生産された学術研究成果を電子的に収集、整 理、保存し、インターネットを通じて無償で提供することを目的として公開して います。

*平成23年度国立情報学研究所最先端学術情報基盤(CSI)構築推進委託事業です。

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Phenotypic characterization and clinical outcome in ampullary adenocarcinoma. 浅野 栄介 Asano Eisuke
Abstract BACKGROUND: Although various features of ampullary adenocarcinoma have been reported, the impact of genetic alterations and rare subtypes on clinical outcome remains unclear. METHODS: We determined the expression of proteins, including MUC1, MUC2, p53, p16, Smad/Dpc4, and β-catenin, and genetic mutations such as KRAS, BRAF, and GNAS mutations in 69 patients with ampullary adenocarcinoma to clarify their relationships with clinicopathological findings and subtypes. RESULTS: Kaplan-Meier survival analysis indicated that abnormal p53 labeling was significantly associated with a shorter overall survival. MUC1-positive and MUC2-negative expressions were significantly associated with lymphatic invasion, pancreatic invasion, lymph node metastasis, and advanced UICC stage. The KRAS mutation was significantly associated with large tumor size and pancreatic invasion. There were 35 intestinal (50%), 15 pancreatobiliary (22%), and 11 mixed subtype (16%) tumors. Patients with the mixed subtype showed significantly poor outcome. The invasiveness of the mixed subtype was similar to that of the pancreatobiliary subtype; moreover, the mixed subtype showed a high incidence of abnormal β-catenin immunolabeling (73%). CONCLUSIONS: Protein expression and genetic mutation are clinically associated with the characteristics of ampullary adenocarcinoma. The mixed subtype may have a distinct tumor nature as compared to other two major subtypes. KEYWORDS: ampullary adenocarcinoma; mixed type; p53; pathologic subtype; β-catenin

Preliminary evidence that rivastigmine-induced inhibition of serum butyrylcholinesterase activity improves behavioral symptoms in Japanese patients with Alzheimer's disease 坂東 伸泰 Bando Nobuyasu
Abstract AIM: To investigate whether the inhibitory rate of serum butyrylcholinesterase (BuChE) activity in Japanese patients with Alzheimer's disease is correlated with cognitive function, behavioral symptoms and caregiver burden. METHODS: A total of 61 patients with mild to moderately severe Alzheimer's disease who were not undergoing cholinesterase enzyme inhibitor/memantine combinatorial treatment received a rivastigmine (18 mg) patch for 24 weeks. The rate of inhibition of BuChE was correlated with scores obtained on cognitive (Mini-Mental State Examination), behavioral (the Japanese version of the modified Crichton Geriatric Behavioral Rating Scale [CGBRS] and Vitality Index [VI]) and burden (the Japanese version of Zarit Burden Inventory [ZBI]) scales; and the Clinical Global Impression of Change scale. RESULTS: The serum BuChE activity showed a significant decrease after 24 weeks compared with baseline (P < 0.001). Overall, significant effects were found in the Mini-Mental State Examination score, VI score and modified CGBRS score. We then divided patient groups into a high inhibitory rate (≥40%) group and a low inhibitory rate (<40%) group; there were significant improvements in the Mini-Mental State Examination score, VI score and modified CGBRS score in both groups. However, favorable results were seen in cooperation, restlessness and leisure on modified CGBRS subscales in the high inhibitory rate group (P < 0.001, P = 0.007, P < 0.001, respectively), and rehabilitation and other activities on VI subscales in the high inhibitory rate group (P = 0.005) compared with those in the low inhibitory rate group. CONCLUSIONS: Demonstrable significant improvements in behavioral symptoms, such as low cooperation, restlessness or low activities in patients with Alzheimer's disease, were achieved on inhibition of BuChE at a rate of 40% or more. Geriatr Gerontol Int 2017; 17: 1306-1312.

Feasibility of Reduced-intensity Cord Blood Transplantation as Salvage Therapy for Graft Failure : Results of a Nationwide Survey of Adult Patients 脇 房子 Waki Fusako
Abstract To evaluate whether rescue with cord blood transplantation (CBT) could improve the poor survival after graft failure (GF), we surveyed the data of 80 adult patients (median age, 51 years) who received CBT within 3 months of GF (primary 64, secondary 16), with fludarabine-based reduced-intensity regimens with or without melphalan, busulfan, cyclophosphamide, and/or 2-4 Gy total-body irradiation (TBI). A median number of 2.4 × 10(7)/kg total nucleated cells (TNC) were infused, and among the 61 evaluable patients who survived for more than 28 days, 45 (74%) engrafted. The median follow-up of surviving patients was 325 days, and the 1-year overall survival rate was 33% despite poor performance status (2-4, 60%), carryover organ toxicities (grade 3/4, 14%), and infections (82%) prior to CBT. Day 100 transplantation-related mortality was 45%, with 60% related to infectious complications. Multivariate analysis showed that the infusion of TNC ≥2.5 × 10(7)/kg and an alkylating agent-containing regimen were associated with a higher probability of engraftment, and that high risk-status at the preceding transplantation and grade 3/4 organ toxicities before CBT were associated with an increased risk of mortality. In conclusion, in an older population of patients, our data support the feasibility of CBT with a reduced-intensity conditioning regimen for GF.

Micro-Vibration Patterns Generated from Shape Memory Alloy Actuators and the Detection of an Asymptomatic Tactile Sensation Decrease in Diabetic Patients 檀上 淳一 DANJO Junichi
Abstract Diabetes mellitus is a group of metabolic diseases that cause high blood sugar due to functional problems with the pancreas or metabolism. Diabetic patients have few subjective symptoms and may experience decreased sensation without being aware of it. The commonly performed tests for sensory disorders are qualitative in nature. The authors pay attention to the decline of the sensitivity of tactile sensations, and develop a non-invasive method to detect the level of tactile sensation using a novel micro-vibration actuator that employs shape-memory alloy wires. Previously, we performed a pilot study that applied the device to 15 diabetic patients and confirmed a significant reduction in the tactile sensation in diabetic patients when compared to healthy subjects. In this study, we focus on the asymptomatic development of decreased sensation associated with diabetes mellitus. The objectives are to examine diabetic patients who are unaware of abnormal or decreased sensation using the quantitative tactile sensation measurement device and to determine whether tactile sensation is decreased in patients compared to healthy controls. The finger method is used to measure the Tactile Sensation Threshold (TST) score of the index and middle fingers using the new device and the following three procedures: TST-1, TST-4, and TST-8. TST scores ranged from 1 to 30 were compared between the two groups. The TST scores were significantly higher for the diabetic patients (P<0.05). The TST scores for the left fingers of diabetic patients and healthy controls were 5.9±6.2 and 2.7±2.9 for TST-1, 15.3±7.0 and 8.7±6.4 for TST-4, and 19.3±7.8 and 12.7±9.1 for TST-8. Our data suggest that the use of the new quantitative tactile sensation measurement device enables the detection of decreased tactile sensation in diabetic patients who are unaware of abnormal or decreased sensation compared to controls.

Retinal Oximetry in a Healthy Japanese Population 中野 裕貴 Nakano Yuki
Abstract PURPOSE: To establish the normative database of retinal oximetry using Oxymap T1 in a healthy Japanese population, and study the reproducibility of the measurements in Japanese. METHODS: We measured oxygen saturation in the major retinal vessels with Oxymap T1 in 252 eyes of 252 healthy Japanese subjects. Fundus images acquired using Oxymap T1 were processed using built-in Oxymap Analyzer software. Reproducibility of retinal oximetry was investigated using 20 eyes of 20 healthy subjects. RESULTS: The mean retinal oxygen saturation of 4 quadrants in healthy Japanese was 97.0 ± 6.9% in arteries and 52.8 ± 8.3% in veins. The mean arteriovenous difference in oxygen saturation was 44.2 ± 9.2%. Both arterial and venous oxygen saturation were significantly lower in the temporal side of the retina, especially in the temporal-inferior vessels. However, the arteriovenous difference in oxygen saturation was limited in the 4 quadrants. Interphotograph, intervisit, and interevaluator intraclass correlation coefficients were 0.936-0.979, 0.809-0.837, and 0.732-0.947, respectively. In the major retinal arteries, oxygen saturation increased with age (r = 0.18, p<0.01), at a rate of 0.67% per 10 years. However, venous oxygen saturation showed no correlation with age. CONCLUSIONS: This study provides the normative database for the Japanese population. The arterial saturation value appears to be higher than other previous studies. Mean retinal oximetry in 4 quadrants with Oxymap T1 has high reproducibility.

Ryanodine receptors contribute to the induction of ischemic tolerance 丸山 恵美
Ischemic tolerance (IT) is induced by a variety of insults to the brain (e.g., nonfatal ischemia, heat and hypoxia) and it provides a strong neuroprotective effect. Although the mechanisms are still not fully elucidated, Ca(2+) is regarded as a key mediator of IT. Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca(2+) from intracellular stores. In brain, neuronal RyRs are thought to play a role in various neuropathological conditions, including ischemia. The purpose of the present study was to investigate the involvement of RyRs in IT. Pretreatment with a RyR antagonist, dantrolene (25mg/kg, i.p), blocked IT in a gerbil global ischemia model, while a RyR agonist, caffeine (100mg/kg, i.p), stimulated the production of IT. In vitro, using rat hippocampal cells, short-term oxygen/glucose deprivation induced preconditioning and RyR antagonists, dantrolene (50 and 100 μM) and ryanodine (100 and 200 μM) prevented it. RyR protein and mRNA levels were transiently decreased after induction of IT. These results suggest that RyRs are involved in the induction of ischemic tolerance.

ABC Dementia Scale : A Quick Assessment Tool for Determining Alzheimer,s Disease Severity 森 崇洋 MORI Takahiro
Background: In this study, we examined the construct validity, concurrent validity concerning other standard scales, intrarater reliability, and changes in scores at 12 weeks of the previously developed ABC Dementia Scale (ABC-DS), a novel assessment tool for Alzheimer's disease (AD). Methods: Data were obtained from 312 patients diagnosed with either AD or mild cognitive impairment. The scores on the ABC-DS and standard scales were compared. Results: The 13 items of the ABC-DS are grouped into three domains, and the domain-level scores were highly correlated with the corresponding conventional scales. Statistically significant changes in assessment scores after 12 weeks were observed for the total ABC-DS scores. Conclusion: Our results demonstrate the ABC-DS to have good validity and reliability, and its usefulness in busy clinical settings.

A quantitative study on splice variants of N-acylethanolamine acid amidase in human prostate cancer cells and other cells 佐倉 雄馬 Sakura Yuma
N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme, hydrolyzing various bioactive N-acylethanolamines with a preference for palmitoylethanolamide. Human NAAA mRNA was previously reported to consist of multiple 3'-end splice variants. However, their tissue distributions and roles have not been examined yet. In the present study, we first identified four major splice variants (tentatively referred to as a1, a2, b2, and c2) in a human prostate cancer cell line LNCaP, which were composed of exons 1-11, exons 1-10 and 12, exons 1-9 and 12, and exons 1-8 and 12, respectively. We next developed quantitative polymerase chain reaction methods to individually quantify these NAAA variants as well as collectively measure all the variants. Among various human prostate cancer cells, the total levels of NAAA mRNAs in androgen-sensitive cells like LNCaP were higher than those in androgen-insensitive cells. In all of these prostate cells and other human cells, variants a1 and b2 showed the highest and lowest expression levels, respectively, among the four variants. Interestingly, ratios of the four variants were different by cell type. Variants a1 and a2 encoded the same full-length NAAA protein, which was catalytically active, while b2 and c2 were translated to C-terminally truncated proteins. As expressed in HEK293 cells these truncated forms were detected as catalytically inactive precursor proteins, but not as mature forms. These results revealed wide distribution of multiple variants of NAAA mRNA in various human cells and suggested that the proteins from some variants are catalytically inactive.

Anatomical Evaluation of Great Saphenous Vein as Material for Conduit in Bypass Surgery for Critical Limb Ischemia 木暮 鉄邦


The role of calcitonin gene-related peptide in migraine prevention by botulinum toxin type A Pleumsamran Juntima Pattamanont


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