| 1.
学位論文(リポジトリ) |
学位
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Kobayashi, Kazuaki
概要:
学位の種類: 博士（医学）. 報告番号: 乙第2225号. 学位記番号: 新大博（医）乙第1797号. 学位授与年月日: 平成30年9月20日<br />新大博（医）乙第1797号
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| 2.
学位論文(リポジトリ) |
学位
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佐藤, 良平
概要:
【背景・目的】膵頭十二指腸切除後の膵外分泌機能低下は，栄養障害を惹き起こす契機となる注意すべき合併症の1つである．膵外分泌機能を評価する方法としてPFD (pancreatic function diagnostant) 試験，呼気試験，糞
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便中脂肪測定があげられるが，現時点で保険適応とされているのはBT-PABA (N-benzoyl-L-tyrosyl-p-aminobenzonic acid) を内服後，尿中PABA排泄率をみるPFD試験のみである．しかしながら，消化・代謝に関わる内服薬の休薬と長時間蓄尿が必要なPFD試験を頻回に繰り返すことは患者負担が大きく，膵外分泌機能を評価する簡便な方法が望まれている．近年ではMultiple- detector row CTの普及により，体積の少ない膵臓でも詳細な画像解析が可能となってきた．本研究の目的は，術前後CT画像解析による測定値が膵外分泌機能低下の指標となり得るかを明らかにすることである． 【対象・方法】2006年10月から2014年3月の間に当施設にて膵頭十二指腸切除術を施行された症例のうち，術後にPFD試験 (尿中PABA排泄率，正常範囲は>70%) を行った38例を対象とした．術前後に施行されたMultiple- detector row CTによるCT画像解析にて膵 volumetry を行い，術前膵 volume，残膵量，残膵率，主膵管径，膵前後径，膵実質厚，膵実質CT値，脾CT値を測定した．さらに，膵実質CT値と脾CT値の比をP／S比率として算出した． 【結果】全症例38例の尿中PABA排泄率の中央値は，56.5% (四分位範囲49.3-64.5) であった．この中央値を参考に，正常値を含む尿中PABA排泄率55%以上の症例を正常・軽度低下群 (20例)，55%未満の症例を高度低下群 (18例) として2群に分類し，両群間にて患者背景およびCT画像解析による各測定値の比較を行った．正常・軽度低下群および高度低下群の尿中PABA排泄率の中央値は，各々64.4% (四分位範囲59.3-67.2) および48.6% (四分位範囲38.6-52.4) であった．両群間で悪性疾患および通常型膵癌の割合に有意差はなかったが，高度低下群において年齢が有意に低く (P=0.030)，術後補助化学療法ありの症例割合が有意に高かった (P=0.004)．また，CT画像解析測定値では，残膵量 (P=0.019)，残膵率 (P=0.002)，術後P／S比率 (P=0.015) の値が高度低下群で有意に低値であった．年齢，通常型膵癌，術後補助化学療法あり，術後膵実質厚，残膵量，残膵率，術後P／S比率の7項目において，ロジスティック回帰分析によって解析を行った結果，膵外分泌機能高度低下群に入ることに有意に独立して寄与する項目は，術後補助化学療法あり (オッズ比9.8，P=0.043)，残膵率33%未満 (オッズ比13.5，P=0.027)，術後P／S比率70%未満 (オッズ比19.6，P=0.015) であった．<br />【考察】膵外分泌機能正常・軽度低下群と高度低下群の両群間において悪性疾患および通常型膵癌の割合では有意差がなく，尿中PABA排泄率低下は術後補助化学療法自体の影響がある可能性が考えられた．さらに術後補助化学療法あり，残膵率，術後P／S比率は独立して膵外分泌機能低下に寄与する項目であると考えられた．特に3次元的計測である残膵率は，膵実質厚や膵前後径に比べやや煩雑ではあるが，より正確な残膵率を反映する測定値であり，さらに術後の膵萎縮を客観的に評価する方法としても有用である．また，術後P／S比率が膵外分泌機能低下を反映するという本研究の結果は，膵実質における脂肪置換や腺房組織の変化が膵実質CT値として表現されるという過去の報告を裏付けるものとなった． 【結論】膵頭十二指腸切除後の膵外分泌機能は術後補助化学療法によって影響を受ける．また，術後CT画像解析から測定した残膵率，術後P／S比率は膵頭十二指腸切除後の膵外分泌機能低下を反映する指標となり得る．<br />学位の種類: 博士（医学）. 報告番号: 乙第2226号. 学位記番号: 新大博（医）乙第1798号. 学位授与年月日: 平成30年9月20日<br />新潟医学会雑誌. 2015, 129(12), 742-750.<br />新大博（医）乙第1798号
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| 3.
学位論文(リポジトリ) |
学位
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Chihara, Makoto
概要:
学位の種類: 博士（医学）. 報告番号: 乙第2227号. 学位記番号: 新大博（医）乙第1799号. 学位授与年月日: 平成30年9月20日<br />新大博（医）乙第1799号
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| 4.
学位論文(リポジトリ) |
学位
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Hoshino, Yoshifumi
概要:
Background: Asthma has a higher prevalence in athlete populations such as Olympic athletes than in the general populatio
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n. Correct diagnosis and management of asthma in athletes is important for symptom control and avoidance of doping accusations. However, few reports are available on asthma treatment in the athlete population in clinical practice. In this study, we focused on the clinical efficacy of inhaled corticosteroid (ICS) for asthma in a Japanese athlete population. Methods: The study subjects included athletes who visited the Niigata Institute for Health and Sports Medicine, Niigata, Japan for athletic tests and who were diagnosed with asthma on the basis of respiratory symptoms and positive results in a bronchodilator or bronchial provocation test such as exercise, hypertonic saline, or methacholine provocation. The athletes received ICS alone for at least 3 months, and the clinical background, sports type, and treatment efficacy were analyzed. Results: The study population comprised 80 athletes (59 men and 21 women) with a median age of 16.0 years. Regarding sports type, 28 athletes engaged in winter sports (35%), 22 in endurance sports (27.5%), and 25 in indoor sports (31.3%). Although ICS is the primary treatment in athlete asthma, 16.3% of the athletes showed an unsatisfactory response to treatment according to the Global Evaluation of Treatment Effectiveness (GETE). These subjects were characterized by a decreased response to methacholine and lower values for FEV_1/FVC and type 2 helper T cell (Th2)-associated biomarkers relative to responsive athletes. In multivariate analysis, FEV_1/FVC and the logarithm to the base 10 of the IgE level were independently associated with the ICS response. Conclusions: These data suggest that ICS is effective for asthma in most athletes. However, certain asthmatic athletes are less responsive to ICS than expected. The pathogenesis in these subjects may differ from that of conventional asthma characterized by chronic allergic airway inflammation.<br />学位の種類: 博士（医学）. 報告番号: 乙第2228号. 学位記番号: 新大博（医）乙第1800号. 学位授与年月日: 平成30年9月20日<br />Allergology International. 2015, 64(2), 145-149.<br />新大博（医）乙第1800号
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| 5.
学位論文(リポジトリ) |
学位
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Hama, Isamu
概要:
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are involved in anti-bacterial immunity. MAIT c
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ells are found in the intestine, but their role and distribution within the large intestine have not been fully elucidated. Therefore, we investigated the distribution of MAIT cells within the cecum and colon. Surgically resected tissues of the cecum and colon were obtained from 4 patients with cecal appendix cancer and 8 patients with colorectal cancer, respectively. Lymphocytes were isolated from the intestinal epithelium (intraepithelial lymphocytes, IELs) and the underlying lamina propria (lamina propria lymphocytes, LPLs), and then, MAIT cells were analyzed by flow cytometry. Compared with the colon, the cecum showed a significantly increased frequency of MAIT cells among IELs (P<0.01). CD69 expression on MAIT cells was significantly increased in the cecum and colon compared with that in the blood, and the frequency of natural killer group 2, member A^+ cells among MAIT cells was significantly increased in the cecum. These results suggest that the distribution of MAIT cells was different between the cecum and colon and that MAIT cells were more likely to be activated, especially in the intestinal epithelium of the cecum than in the colon and blood.<br />学位の種類: 博士（医学）. 報告番号: 甲第4490号. 学位記番号: 新大院博（医）甲第827号. 学位授与年月日: 平成30年9月20日<br />新大院博（医）甲第827号
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| 6.
学位論文(リポジトリ) |
学位
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Kobayashi, Takamasa
概要:
Background: Prognosis of patients with hepatocellular carcinoma (HCC) who undergo transcatheter intra-arterial therapies
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including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy is affected by many clinical factors including liver function and tumor progression. However, the effect of body composition such as skeletal muscle and visceral and subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of these patients remains unclear. We investigated the prognostic value of body composition in HCC patients treated with transcatheter intra-arterial therapies. Patients and Methods: This study retrospectively evaluated 100 HCC patients treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas of skeletal muscle, VAT, and SAT were measured on computed tomography images at third lumbar vertebra level and normalized by the height squared to calculate the skeletal muscle index, VAT index, and SAT index (SATI). Visceral to subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS) was compared between high- and low-index groups for each body composition. Furthermore, prognostic significance was assessed by univariate and multivariate analyses using Cox proportional hazards models. Results: Among the body composition indexes, only SATI could significantly differentiate OS (P= .012). Multivariate analysis showed that SATI (low- vs. high-SATI; hazard ratio [HR], 2.065; 95% confidence interval [CI], 1.187-3.593; P= .010), serum albumin (<3.5 vs. ≥3.5 g/dL; HR, 2.007; 95% CI, 1.037-3.886; P= .039), serum alpha-fetoprotein (<20 vs. ≥20 ng/mL; HR, 0.311; 95% CI, 0.179-0.540; P< .001), and mRECIST assessment (complete response + partial response + stable disease vs. progressive disease; HR, 0.392; 95% CI, 0.221-0.696; P= .001) were indicated as independent prognostic factors for OS. Conclusions: High SAT volume is associated with better survival outcomes in HCC patients treated with transcatheter intra-arterial therapies. Elucidation of the mechanisms regulating SAT volume may offer new therapeutic strategy in these patients.<br />学位の種類: 博士（医学）. 報告番号: 甲第4491号. 学位記番号: 新大院博（医）甲第828号. 学位授与年月日: 平成30年9月20日<br />Cancer Management and Research. 2018, 10, 2231-2239.<br />新大院博（医）甲第828号
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| 7.
学位論文(リポジトリ) |
学位
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Seino, Satoshi
概要:
The high heterogeneity of hepatocellular carcinomas (HCCs) complicates stratification of HCC patients for treatment. The
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refore, it is necessary to establish a comprehensive panel of HCC biomarkers related to tumour behaviour and cancer prognosis. Resected HCCs from 251 patients were stained for hepatic progenitor cell (HPC) markers epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), delta-like 1 homolog (DLK1), and cytokeratin 19 (CK19). Staining patterns were analysed for their prognostic association with relapse-free survival and overall survival. α-Fetoprotein (AFP), lectin-reactive α-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin (DCP) were assessed as indicators of HPC protein expression. Expression pattern of HPC markers correlated with tumour malignancy indicated by high AFP/AFP-L3 serum levels, more frequent vascular invasion, and poorer tumour differentiation. EpCAM expression, DCP ≥300 mAU/ml, age ≥60, and Child-Pugh score grade B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation. Expression of two or more HPC markers was a significant predictor of poor HCC outcome and serum levels of AFP/AFP-L3 correlated with the expression of HPC proteins. Our study paved the way for further elucidation of the association among HPC markers, serum tumour markers, and HCC clinical outcome for precision medicine.<br />学位の種類: 博士（医学）. 報告番号: 甲第4492号. 学位記番号: 新大院博（医）甲第829号. 学位授与年月日: 平成30年9月20日<br />Oncotarget. 2018, 9(31), 21844-21860.<br />新大院博（医）甲第829号
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| 8.
学位論文(リポジトリ) |
学位
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Yuza, Kizuki
概要:
学位の種類: 博士（医学）. 報告番号: 甲第4493号. 学位記番号: 新大院博（医）甲第830号. 学位授与年月日: 平成30年9月20日<br />新大院博（医）甲第830号
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| 9.
学位論文(リポジトリ) |
学位
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笹川, 泰司
概要:
Dipeptidyl peptidase-4 (DPP-4) 阻害薬は血糖改善作用だけでなく、それには依存しないアルブミン尿の減少などの腎臓保護効果をもたらす可能性が示唆されているが、腎近位尿細管へ及ぼす影響も含めその詳細は未だに不明である
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。我々は以前から、近位尿細管管腔側に発現するメガリンに着目し、その尿中排泄量の測定法を開発するとともに、それらが糖尿病性腎症において腎障害を反映する新しいバイオマーカーとなり得るかを検討してきた。今回、糖尿病性腎症1～3期の2型糖尿病患者113名に新規にDPP-4阻害薬であるシタグリプチンを追加し、使用前後で血糖、血圧、腎機能、尿中C-メガリンをはじめとした近位尿細管関連の尿中バイオマーカーに及ぼす影響を前向きに調査するとともに、アルブミン尿の減少を予測する因子の検討を行った。結果は、開始12か月でHbA1cおよびeGFR (推算糸球体濾過量) は有意に低下したが、尿中アルブミン/クレアチニン比 (ACR) には有意差がみられなかった。シタグリプチンによるアルブミン尿改善効果の要因を検討するため、12か月後の尿中ACRが20％以上減少していた群とそれ以外の群を3か月時点で比較したところ、12か月後の尿中ACRが20%以上減少する予測因子は、3か月後の尿中α1-ミクログロブリン/クレアチニン比 (α1-MG/Cr) の有意な減少であった。α1-MGはメガリンのリガンドであるため、尿中α1-MG/Crの減少は近位尿細管機能の改善ということだけでなく、メガリンの再吸収機能が回復したことを示唆している。さらに、尿中ACR、α1-MG/Crが減少した群で尿中C-メガリン/Cr量が不変であったことから、メガリンのタンパク再吸収機能の回復が近位尿細管での代謝負荷には結びついていないことを示唆していると考えられた。2型糖尿病症例において、シタグリプチン開始3か月後に尿中α1-MG/Crが減少することは、血糖および血圧とは独立して、12か月後の尿中ACRの減少を予測する因子であった。今後、より詳細な検討を行い、DPP-4阻害薬による近位尿細管への影響に関連した腎保護効果を明らかにしていく予定である。<br />学位の種類: 博士（医学）. 報告番号: 甲第4494号. 学位記番号: 新大院博（医）甲第831号. 学位授与年月日: 平成30年9月20日<br />新大院博（医）甲第831号
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| 10.
学位論文(リポジトリ) |
学位
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Kobayashi, Akira
概要:
Background: Thyroid function of asphyxiated newborns who received hypothermia therapy and its relation to neurological o
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utcome are not well described. Methods: This is a prospective study measuring thyroid function of 12 asphyxiated newborns who received hypothermia therapy. We measured serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels on admission, 24, 72, and 96 hours after birth, and at discharge (17-54 days). Twelve newborns were divided into two groups based on the presence of brain injury on head magnetic resonance imaging findings (six in the abnormal imaging group and six in the normal imaging group) and their thyroid functions were compared between the twogroups. Results: Serum TSH levels were within a normal range. Serum FT3 and FT4 levels remained low at 24, 72, and 96 hours after birth, and returned to a normal range at discharge. There was no significant difference in serum TSH levels between the two groups. However, serum FT4 levels at 72 hours after birth, and serum FT3 and FT4 levels at 96 hours after birth were significantly lower in the abnormal imaging group than those in the normal imaging group (p=0.03, p=0.02, and p=0.01, respectively). Conclusion: These results suggest that asphyxiated newborns have transient low thyroid hormone levels at 24-96 hours after birth. Serum FT3 and FT4 levels between 72 and 96 hours after birth may predict brain injury of asphyxiated newborns.<br />学位の種類: 博士（医学）. 報告番号: 甲第4495号. 学位記番号: 新大院博（医）甲第832号. 学位授与年月日: 平成30年9月20日<br />Pediatrics International. 2018, 60(5), 433-437. First published: 20 February 2018.<br />新大院博（医）甲第832号
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| 11.
学位論文(リポジトリ) |
学位
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Maniwa, Keiichi
概要:
To understand the neural mechanisms underlying the therapeutic effects of crossing nerve transfer for brachial plexus in
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juries in human patients, we investigated the cortical responses after crossing nerve transfer in mice using conventional and tomographic optical imaging. The distal cut ends of the left median and ulnar nerves were connected to the central cut ends of the right median and ulnar nerves with a sciatic nerve graft at 8 weeks of age. Eight weeks after the operation, the responses in the primary somatosensory cortex (S1) elicited by vibratory stimulation applied to the left forepaw were visualized based on activity-dependent flavoprotein fluorescence changes. In untreated mice, the cortical responses to left forepaw stimulation were mainly observed in the right S1. In mice with nerve crossing transfer, cortical responses to left forepaw stimulation were observed in the left S1 together with clear cortical responses in the right S1. We expected that the right S1 responses in the untreated mice were produced by thalamic inputs to layer IV, whereas those in the operated mice were mediated by callosal inputs from the left S1 to layer II/III of the right S1. To confirm this hypothesis, we performed tomographic imaging of flavoprotein fluorescence responses by macroconfocal microscopy. Flavoprotein fluorescence responses in layer IV were dominant compared to those in layer II/III in untreated mice. In contrast, responses in layer II/III were dominant compared to those in layer IV in operated mice. The peak latency of the cortical responses in the operated mice was longer than that in the untreated mice. These results confirmed our expectation that drastic reorganization in the cortical circuits was induced after crossing nerve transfer in mice.<br />学位の種類: 博士（医学）. 報告番号: 甲第4496号. 学位記番号: 新大院博（医）甲第833号. 学位授与年月日: 平成30年9月20日<br />PLoS ONE. 2018, 13(2), e0193017.<br />新大院博（医）甲第833号
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| 12.
学位論文(リポジトリ) |
学位
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Yamagishi, Tatsuya
概要:
Clustered protocadherins (Pcdhs) are neuronal cell adhesion molecules characterized by hemophilic adhesion between the t
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etramers of 58 distinct isoforms in mice. The diversity of Pcdhs and resulting highly-specific neuronal adhesion may be required for the formation of neural circuits for executing higher brain functions. However, this hypothesis remains to be tested, because knockout of Pcdh genes produces abnormalities that may interfere with higher brain functions indirectly. In Pcdh-α1,12 mice, only α1, α12 and two constitutive isoforms are expressed out of 14 isoforms. The appearance and behavior of Pcdh-α1,12 mice are similar to those of wild-type mice, and most abnormalities reported in Pcdh-α knockout mice are not present in Pcdh-α1,12 mice. We examined Pcdh-α1,12 mice in detail, and found that cortical depression induced by sensory mismatches between vision and whisker sensation in the visual cortex was impaired. Since Pcdh-α is densely distributed over the cerebral cortex, various types of higher function are likely impaired in Pcdh-α1,12 mice. As expected, visual short-term memory of space/shape was impaired in behavioral experiments using space/shape cues. Furthermore, behavioral learning based on audio-visual associative memory was also impaired. These results indicate that the molecular diversity of Pcdh-α plays essential roles for sensory integration and short-term memory.<br />学位の種類: 博士（医学）. 報告番号: 甲第4497号. 学位記番号: 新大院博（医）甲第834号. 学位授与年月日: 平成30年9月20日<br />Scientific Reports. 2018, 8, 9616.<br />新大院博（医）甲第834号
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| 13.
学位論文(リポジトリ) |
学位
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Wakamatsu, Takuya
概要:
In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and morta
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lity. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-_K, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay. IS induced macrophage pro-IL-1β mRNA expression, although mature IL-1 was only slightly increased. IS increased AhR and the AhR-related mRNA expression; this change was suppressed by administration of proteasome inhibitor. IS promoted phosphorylation of NF-_KB p65 and MAPK enzymes; the reaction and IL-1 expression were inhibited by BAY11-7082, an inhibitor of NF-_KB. In contrast, IS decreased NLRP3 and did not change ASC, pro-caspase 1, or caspase-1 activation. IS-inducing inflammation in macrophages results from accelerating AhR-NF-_KB/MAPK cascades, but the NLRP3 inflammasome was not activated. These reactions may restrict mature IL-1β production, which may explain sustained chronic inflammation in CKD patients.<br />学位の種類: 博士（医学）. 報告番号: 甲第4498号. 学位記番号: 新大院博（医）甲第835号. 学位授与年月日: 平成30年9月20日<br />Toxins. 2018, 10, 124.<br />新大院博（医）甲第835号
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| 14.
学位論文(リポジトリ) |
学位
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14. Ceramide species are elevated in human breast cancer and are associated with less aggressiveness
Moro, Kazuki
概要:
Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sp
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hingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients.<br />学位の種類: 博士（医学）. 報告番号: 甲第4499号. 学位記番号: 新大院博（医）甲第836号. 学位授与年月日: 平成30年9月20日<br />Oncotarget. 2018, 9(28), 19874-19890.<br />新大院博（医）甲第836号
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| 15.
学位論文(リポジトリ) |
学位
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Ishiguro, Hajime
概要:
学位の種類: 博士（医学）. 報告番号: 甲第4500号. 学位記番号: 新大院博（医）甲第837号. 学位授与年月日: 平成30年9月20日<br />新大院博（医）甲第837号
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| 16.
学位論文(リポジトリ) |
学位
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Mitadera, Yuji
概要:
The hospital environment in Japan has changed drastically lately. Its unpredictability has increased the need for hospit
…
als to select management strategies to clarify their course. However, research on Japanese hospitals’ management strategies has only recently begun with too few studies in this area. Hence, this study clarifies the management strategies of Japanese private hospitals. It explores the hospital characteristics that affect strategy selection. A questionnaire was mailed to 5682 private medical institutions in 2013, and 459 responses with no missing data were used for analysis. Factor analysis yielded four factors: “bed conversion and downsizing (Factor 1),” “diversification of medical and nursing care (Factor 2),” “expansion in business scale (Factor 3),” and “expansion of income from non-insured medical care (Factor 4)”. Logistic regression analysis revealed that Year Founded (before 1965), Hospital Location (municipalities with populations smaller than 100,000), Hospital Type (psychiatric hospitals and mixed-care hospital), and Hospital Income and Expenditure (deficit) had significant positive impacts on the choice of Factor 1. For Factor 2, Hospital Type (sanatorium ward and mixed-care hospitals) and Hospital Income and Expenditure (constant surplus) had positive impacts. For Factor 3, Hospital Type (general hospital) and Bed Counts (more than 200) had positive impacts. For Factor4, Hospital Type (general hospital) had positive impacts. In other words, older hospitals, hospitals in rural areas, psychiatric hospitals, mixed-care hospitals, and hospitals with deficits tended to choose bed conversion and downsizing. Sanatorium ward hospitals, mixed-care hospitals, and hospitals with a constant surplus tended to choose diversification of medical and nursing care. General hospitals and large hospitals tended to choose expansion in scale, and general hospitals tended to choose expansion into non-insured medical care. The planning of mid- to long-term management strategies suitable for each hospital and their steady execution are required.<br />学位の種類: 博士（医学）. 報告番号: 甲第4501号. 学位記番号: 新大院博（医）甲第838号. 学位授与年月日: 平成30年9月20日<br />Health. 2017, 9, 1494-1508.<br />新大院博（医）甲第838号
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| 17.
学位論文(リポジトリ) |
学位
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Sato, Nobuhiro
概要:
Background: Long-term care facilities for older people play an important role as alternatives to family care in an aging
…
society. This study aimed to assess staffing problems linked to emergency healthcare for residents of these facilities, and to investigate the relationship between these problems and the characteristics of the facilities. Methods: The study surveyed managers of long-term care facilities for older people in a Japanese urban area between September and December 2014. The type of care facility, the number of staff and any problems providing or accessing emergency healthcare for the residents were evaluated. Multiple logistic regression analysis was used to explore the factors common to facilities reporting staffing problems linked to emergency healthcare of residents. Results: In total, 321 long-term care facilities were eligible for this study and 226 (70%) returned the questionnaire. We compared the characteristics of facilities reporting and not reporting staffing problems in emergency healthcare of residents. The type of care facility was significantly associated with staffing problems in emergency healthcare of residents both during the day (p< 0.01) and at night (p= 0.04). The facilities most likely to report problems were group homes for older people with dementia, because of staffing shortages. Conclusions: Problems in emergency healthcare systems in Japanese long-term care facilities for older people varied by type of care facility. Our data underscore the need for telemedicine and consideration of mergers between smaller facilities such as group homes for older people with dementia.<br />学位の種類: 博士（医学）. 報告番号: 甲第4502号. 学位記番号: 新大院博（医）甲第839号. 学位授与年月日: 平成30年9月20日<br />Health. 2017, 9, 1159-1175.<br />新大院博（医）甲第839号
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| 18.
学位論文(リポジトリ) |
学位
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Savitskaya, Anna
概要:
The architecture of the genome influences the functions of DNA from bacteria to eukaryotes. Intrinsically disordered reg
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ions (IDR) of eukaryotic histones have pivotal roles in various processes of gene expression. IDR is rare in bacteria, but interestingly, mycobacteria produce a unique histone-like protein, MDP1 that contains a long C-terminal IDR. Here we analyzed the role of IDR in MDP1 function. By employing Mycobacterium smegmatis that inducibly expresses MDP1 or its IDR-deficient mutant, we observed that MDP1 induces IDR-dependent DNA compaction. MDP1-IDR is also responsible for the induction of growth arrest and tolerance to isoniazid, a front line tuberculosis drug that kills growing but not growth-retardated mycobacteria. We demonstrated that MDP1-deficiency and conditional knock out of MDP1 cause spreading of the M. smegmatis genome in the stationary phase. This study thus demonstrates for the first time a C-terminal region-dependent organization of the genome architecture by MDP1, implying the significance of IDR in the function of bacterial histone-like protein.<br />学位の種類: 博士（医学）. 報告番号: 甲第4503号. 学位記番号: 新大院博（医）甲第840号. 学位授与年月日: 平成30年9月20日<br />Scientific Reports. 2018, 8, 8197.<br />新大院博（医）甲第840号
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| 19.
学位論文(リポジトリ) |
学位
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Suzuki, Taku
概要:
This study aimed to investigate whether the jaw-opening (JOR) and jaw-closing reflexes (JCR) are modulated during not on
…
ly peripherally, but also centrally, evoked swallowing. Experiments were carried out on 24 adult male Japanese white rabbits. JORs were evoked by trigeminal stimulation at 1 Hz for 30 s. In the middle 10 s, either the superior laryngeal nerve (SLN) or cortical swallowing area (Cx) was simultaneously stimulated to evoke swallowing. The peak-to-peak JOR amplitude was reduced during the middle and late 10-s periods (i.e., during and after SLN or Cx stimulation), and the reduction was dependent on the current intensity of SLN/Cx stimulation: greater SLN/Cx stimulus current resulted in greater JOR inhibition. The reduction rate was significantly greater during Cx stimulation than during SLN stimulation. The amplitude returned to baseline 2 min after 10-s SLN/Cx stimulation. The effect of co-stimulation of SLN and Cx was significantly greater than that of SLN stimulation alone. There were no significant differences in any parameters of the JCR between conditions. These results clearly showed that JOR responses were significantly suppressed, not only during peripherally evoked swallowing but also during centrally evoked swallowing, and that the inhibitory effect is likely to be larger during centrally compared with peripherally evoked swallowing. The functional implications of these results are discussed.<br />学位の種類: 博士（歯学）. 報告番号: 甲第4504号. 学位記番号: 新大院博（歯）甲第412号. 学位授与年月日: 平成30年9月20日<br />新大院博（歯）甲第412号
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| 20.
学位論文(リポジトリ) |
学位
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波多, 幸江
概要:
学位の種類: 博士（学術）. 報告番号: 甲第4505号. 学位記番号: 新大院博（学）甲第93号. 学位授与年月日: 平成30年9月20日<br />新大院博（学）甲第93号
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| 21.
学位論文(リポジトリ) |
学位
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Tenkovskaia, Liudmila
概要:
学位の種類: 博士（学術）. 報告番号: 甲第4506号. 学位記番号: 新大院博（学）甲第215号. 学位授与年月日: 平成30年9月20日<br />新大院博（学）甲第215号
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| 22.
学位論文(リポジトリ) |
学位
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Tran, Dinh Minh
概要:
学位の種類: 博士（学術）. 報告番号: 甲第4507号. 学位記番号: 新大院博（学）甲第216号. 学位授与年月日: 平成30年9月20日<br />新大院博（学）甲第216号
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| 23.
学位論文(リポジトリ) |
学位
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Yu, Hui
概要:
学位の種類: 博士（理学）. 報告番号: 甲第4508号. 学位記番号: 新大院博（理）甲第433号. 学位授与年月日: 平成30年9月20日<br />新大院博（理）甲第433号
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| 24.
学位論文(リポジトリ) |
学位
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工藤, 慈
概要:
学位の種類: 博士（工学）. 報告番号: 甲第4509号. 学位記番号: 新大院博（工）甲第480号. 学位授与年月日: 平成30年9月20日<br />新大院博（工）甲第480号
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| 25.
学位論文(リポジトリ) |
学位
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梅原, 康宏
概要:
学位の種類: 博士（工学）. 報告番号: 甲第4510号. 学位記番号: 新大院博（工）甲第481号. 学位授与年月日: 平成30年9月20日<br />新大院博（工）甲第481号
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| 26.
学位論文(リポジトリ) |
学位
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石井, 治彦
概要:
学位の種類: 博士（工学）. 報告番号: 甲第4511号. 学位記番号: 新大院博（工）甲第482号. 学位授与年月日: 平成30年9月20日<br />新大院博（工）甲第482号
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| 27.
学位論文(リポジトリ) |
学位
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傳谷, 典子
概要:
学位の種類: 博士（工学）. 報告番号: 甲第4512号. 学位記番号: 新大院博（工）甲第483号. 学位授与年月日: 平成30年9月20日<br />新大院博（工）甲第483号
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| 28.
学位論文(リポジトリ) |
学位
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安中, 裕大
概要:
学位の種類: 博士（工学）. 報告番号: 甲第4513号. 学位記番号: 新大院博（工）甲第484号. 学位授与年月日: 平成30年9月20日<br />新大院博（工）甲第484号
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| 29.
学位論文(リポジトリ) |
学位
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Zhang, Mingyu
概要:
学位の種類: 博士（工学）. 報告番号: 甲第4514号. 学位記番号: 新大院博（工）甲第485号. 学位授与年月日: 平成30年9月20日<br />新大院博（工）甲第485号
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| 30.
学位論文(リポジトリ) |
学位
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Takamatsu, Takeshi
概要:
学位の種類: 博士（農学）. 報告番号: 甲第4515号. 学位記番号: 新大院博（農）甲第185号. 学位授与年月日: 平成30年9月20日<br />Frontiers in Plant Science. 2018, 9, 266.<b
…
r />新大院博（農）甲第185号
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| 31.
学位論文(リポジトリ) |
学位
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Sandakova, Nadezhda
概要:
The overall efficiency of Russia's agricultural machinery industry (AMI) was seriously undermined during the period of s
…
tagnation following the collapse of the Soviet Union. Western sanctions against Russia and counter-sanctions that began in 2014 revealed the problem of extremely high import dependence in the agrarian sector in general and AMI in particular, which led the Russian government to shift urgently to an import substitution policy based on innovative strategies. This study first overviewed the current situation and identified both positive changes and immense problems remaining in the industry and stated that traditional strategies of industrial development could not provide the necessary solutions, given the need for quick improvements. Transition to the innovative path of the AMI development requires the acceleration of scientific and technical progress and the introduction of new technologies. The implementation of industrial clusters is an effective instrument for the development of an innovative economy. The main objective of this study was to propose that the formation of a cluster in the Rostov region, where the most efficient AM manufacturers have been traditionally concentrated, would positively affect the domestic AMI in general and enhance the individual competitiveness of companies making up the cluster. Through the manufacturers' actual performance analysis, this study demonstrated that the region was an appropriate location for the rational import substitution program realization. Using an AHP model, it determined the most pertinent participants for the potential cluster and proposed a model for cluster formation. The actual level of “innovative readiness” of AM companies in the Rostov region and their potential profitability in the cluster compared with individual profitability was estimated using economic and mathematical modeling tools. Based on the calculations, it was concluded that functioning under the cluster was more economically efficient than functioning as independent enterprises for Rostselmash, Klever, and Salskselmash companies. The study proved that the formation of the cluster, centered on the manufacturer Rostselmash, would positively affect the productivity, innovation activity and development of all enterprises comprising the cluster. The development of its domestic AMI would allow Russia to conduct an independent policy of import substitution for food products, machinery, and equipment, and contribute to the food security of the country.<br />学位の種類: 博士（農学）. 報告番号: 甲第4516号. 学位記番号: 新大院博（農）甲第186号. 学位授与年月日: 平成30年9月20日<br />新大院博（農）甲第186号
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| 32.
学位論文(リポジトリ) |
学位
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Sandakov, Tsyden
概要:
Nowadays there is a gap between the equipment available in the Russian market and agricultural stakeholders’ need for th
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e equipment embracing modern technologies for grain cultivation. Therefore, the purpose of this study is to develop a resource-saving Deep Placement Fertilizer Applicator (DPFA) prototype for grain production in Russia. To achieve the goal of the research, this study first determined the impact of different tillage systems on the grain yield and costs in the Republic of Buryatia, Russia. The minimum tillage and no-tillage systems present expedient alternatives to the conventional system of soil tillage, due to crop yield increase, cost reduction and to their conservation effects on the soil as compared to the conventional system. The minimum tillage method presupposes the use of subsoil and deep soil tillage devices, such as the chisel plow. Therefore, an advanced, resource-saving chisel plow for grain production in the Republic of Buryatia was developed. The proposed model reduced resistance of soil to the working parts and increased operational reliability of the device. Data of the equivalent stress, equivalent elastic strain, total deformation, and mass were obtained using the FEM to determine the optimum design of the chisel plow; these values for the optimized construction have decreased by 4.6, 2.1, 5, and 8% compared with the original design, respectively. Optimization of the chisel plow design was achieved by decreasing its mass and increasing its service life. Finally, a resource-saving DPFA prototype with optimum design of chisel plow for grain production was developed. The characteristics of new DPFA prototype are Deep Placement fertilization, which is one of environmentally friendly farming method, and saving on labor costs because it simultaneously performs tillage, fertilization, and seeding. Furthermore, top dressing application is not required because the effect of fertilizers is kept over a more extended period by the Deep Placement fertilization. For the DFPA prototype fabrication, the idea, the 2D and 3D engineering drawings of the DPFA were submitted to the Project of development of high-speed seeder with DPFA for the large-scale Russian farming (Project). The Project has been realized between Niigata University and Primorskaya State Academy of Agriculture from November 1, 2017. The fabrication of the proposed chisel plow was made during the first stage of the Project.<br />学位の種類: 博士（農学）. 報告番号: 甲第4517号. 学位記番号: 新大院博（農）甲第187号. 学位授与年月日: 平成30年9月20日<br />新大院博（農）甲第187号
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| 33.
学位論文(リポジトリ) |
学位
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田中, 美央
概要:
学位の種類: 博士（保健学）. 報告番号: 甲第4518号. 学位記番号: 新大院博（保）甲第28号. 学位授与年月日: 平成30年9月20日<br />新大院博（保）甲第28号
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| 34.
学位論文(リポジトリ) |
学位
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Bogdanova, Dana
概要:
Organized tissue structure in the secondary lymphoid organs (SLOs) tightly depends on the development of fibroblastic st
…
romal cells (FSCs) of mesenchymal origin; however, the mechanisms of this relationship are poorly understood. In this study, we specifically inactivated the canonical NF-kB pathway in FSCs in vivo by conditionally inducing IkBa mutant in a Ccl19-IkBSR mouse system in which NF-kB activity is likely to be suppressed in fetal FSC progenitors. Given that NF-kB activation in fetal FSCs is essential for SLO development, the animals were expected to lack SLOs. However, all SLOs were preserved in Ccl19-IkBSR mice. Instead, the T cell area was severely disturbed by the lack of CCL21-expressing FSCs, whereas the follicles and associated FSC networks were formed. Fate mapping revealed that IkBSR-expressing cells constituted only a small fraction of stromal compartment outside the follicles. Taken together, our findings indicate an essential role of the canonical NF-kB pathway activity in the development of three FSC subsets common to SLOs and suggest transient or stochastic CCL19 expression in FSC progenitors and a compensatory differentiation program of follicular FSCs.<br />学位の種類: 博士（医学）. 報告番号: 乙第2229号. 学位記番号: 新大博（医）乙第1801号. 学位授与年月日: 平成31年3月15日<br />The Journal of immunology. 2018, 201(12), 3580-3586.<br />新大博（医）乙第1801号
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| 35.
学位論文(リポジトリ) |
学位
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Ito, Masayuki
概要:
Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is
…
caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP. Case presentation: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage. She tested negative for GM-CSF autoantibodies, with no underlying disease. Her serum GM-CSF level was elevated (91.3 pg/mL), indicating GM-CSF signaling impairment and genetic defects in the GM-CSF receptor. GM-CSF-stimulated phosphorylation in signal transducer and activator of transcription 5 (STAT5) was not observed, and GM-CSF-Rα expression was defective in her blood cells. Genetic screening revealed a homozygous, single-base C > T mutation at nt 508—a nonsense mutation that yields a stop codon (Q170X)—in exon 7 of CSF2RA. High-resolution analysis of single nucleotide polymorphism array confirmed a 22.8-Mb loss of heterozygosity region in Xp22.33p22.11, encompassing the CSF2RA gene. She was successfully treated with whole lung lavage (WLL), which reduced the serum levels of interleukin (IL)-2, IL-5, and IL-17, although IL-3 and M-CSF levels remained high. Conclusions: This is the first known report of elderly-onset hPAP associated with a CSF2RA mutation, which caused defective GM-CSF-Rα expression and impaired signaling. The analyses of serum cytokine levels during WLL suggested that GM-CSF signaling might be compensated by other signaling pathways, leading to elderly-onset PAP.<br />学位の種類: 博士（医学）. 報告番号: 乙第2230号. 学位記番号: 新大博（医）乙第1802号. 学位授与年月日: 平成31年3月15日<br />BMC Pulmonary Medicine. 2017, 17:40<br />新大博（医）乙第1802号
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| 36.
学位論文(リポジトリ) |
学位
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Furukawa, Toshiki
概要:
学位の種類: 博士（医学）. 報告番号: 乙第2231号. 学位記番号: 新大博（医）乙第1803号. 学位授与年月日: 平成31年3月15日<br />新大博（医）乙第1803号
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| 37.
学位論文(リポジトリ) |
学位
|
坂本, 武也
概要:
新潟県佐渡市では，超高齢社会，医療・介護資源不足の中で提供できる医療を維持すべく，病院・医科診療所・歯科診療所・調剤薬局・介護施設を結ぶ地域医療連携ネットワークシステムが平成25年4月に稼働した．各参加施設より，診療報酬明細情報からの病名・
…
院内処方内容・注射内容・手術を含む処置内容，外注検査業者を含む検査システムからの検体検査結果，画像機器からの検査画像，調剤薬局システムからの院外処方内容を収集し，データセンターに格納することで情報の提供・参照を双方向で行うネットワークシステムである．各施設の対象機器を個別につなぐ作業が必要であるが，電子カルテを導入していない医療機関からの情報収集が可能であり，本来の地域医療連携および機能分担に必要な情報共有基盤の構築を目指している．平成26年2月現在，参加対象施設の7割の参加，佐渡市民の2割の同意を得ており，機能的な医療連携および介護領域との連携が期待される．<br />学位の種類: 博士（医学）. 報告番号: 乙第2232号. 学位記番号: 新大博（医）乙第1804号. 学位授与年月日: 平成31年3月15日<br />新潟医学会雑誌. 2015, 129(4), 187-198.<br />新大博（医）乙第1804号
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| 38.
学位論文(リポジトリ) |
学位
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佐藤, 洋
概要:
【緒言】大腸癌化学療法の進歩は著しく，切除不能・再発大腸癌の生存期間は 2年を超えている．大腸癌領域では，KRAS遺伝子測定が抗epidermal growth factor reseptor (EGFR)抗体薬の治療効果予測囚子としてその
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地位を確立している ．しかし，KRAS遺伝子野生型であっても奏効率の上乗せは 10-30%にすぎず，KRAS遺伝子を介さない別経路の存在が注目されている ．NAD (P) H: quinone oxidoreductase 1 (NQOl) は，抗癌剤や放射線照射耐性に関与する抗酸化ストレス蛋白として知られているが，大腸癌におけるKRAS遺伝子変異，予後との関連は明らかになっていない．本研究の目的は，KRAS遺伝子野生型および変異型切除不能・再発大腸癌における NQOl発現が予後に関与するかを検証することである ． 【方法】2007年3月から2013年1月までに当科でKRAS遺伝子野生型および変異型切除不能・再発大腸癌に対して治療を行った51例を対象とした．対象症例の大腸癌原発巣標本において，NQOlモノ クローナル抗体を用いた免疫組織化学検査を行い，NQOlの発現を解析した．NQOlの発現を陽性および陰性の2群に分類し，臨床病理学的特徴および予後を統計学的に検討した． 【結果】男性29例，女性22例で年齢中央値は62歳（範囲 ：17-79歳）， KRAS遺伝子野生型は 33例 (64.7%),変異型は 18例 (35.3%)であった.NQOl発現陽性群が 40例 (78.4%),陰性群が 11例 (21.6%)であった.NQOl発現陽性群，陰性群の間で臨床病理学的囚子に有意差はみられなかった.生存期間の検討では，NQOl発現陽性群と陰性群，KRAS追伝子野生型と変異型の間で有意差は認められなかった (P=0.453, P=0.089). しかし，NQOl発現解析，KRAS遺伝子変異検査の両者を組み合わせることによって，生存期間が有意に層別化された(P = 0.049).KRAS野生型かつ NQOl発現陰性群の生存期間中央値 (MST) は46か月であり，KRAS変異型かつNQOl発現陽性群の 21か月 (P=0.042), KRAS変異型かつNQOl発現陰性群の15か月(P= 0.007)と比較して有意に予後良好であった.KRAS遺伝子野生型に限ると，NQOl発現陰性群のMSTは46か月，NQOl発現陽性群の MSTは26か月であり，NQOl発現陰性群の予後が良好な傾向を示した (P= 0.074). 【結論】NQOl発現解析とKRAS遺伝子変異検査の両者を行うことにより，切除不能 ・再発大腸癌の予後が有意に層別化される．<br />学位の種類: 博士（医学）. 報告番号: 乙第2233号. 学位記番号: 新大博（医）乙第1805号. 学位授与年月日: 平成31年3月15日<br />新潟医学会雑誌. 2015, 129(6), 300-308.<br />新大博（医）乙第1805号
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| 39.
学位論文(リポジトリ) |
学位
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Tanaka, Ryo
概要:
学位の種類: 博士（医学）. 報告番号: 乙第2234号. 学位記番号: 新大博（医）乙第1806号. 学位授与年月日: 平成31年3月15日<br />新大博（医）乙第1806号
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| 40.
学位論文(リポジトリ) |
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Tamura, Hiroshi
概要:
学位の種類: 博士（医学）. 報告番号: 乙第2235号. 学位記番号: 新大博（医）乙第1807号. 学位授与年月日: 平成31年3月15日<br />新大博（医）乙第1807号
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| 41.
学位論文(リポジトリ) |
学位
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Yagi, Ryoma
概要:
学位の種類: 博士（医学）. 報告番号: 乙第2236号. 学位記番号: 新大博（医）乙第1808号. 学位授与年月日: 平成31年3月15日<br />新大博（医）乙第1808号
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| 42.
学位論文(リポジトリ) |
学位
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Terashima, Hiroko
概要:
Purpose: To determine the efficacy of the combination therapy of intravitreal ranibizumab (IVR) and 577-nm yellow laser
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subthreshold micropulse laser photocoagulation (SMLP) for macular edema secondary to branch retinal vein occlusion cystoid macular edema. Methods: Retrospective, consecutive, case–control study. Forty-six eyes of 46 patients with treatment-naive branch retinal vein occlusion cystoid macular edema were enrolled. The IVR + SMLP group consisted of 22 patients who had undergone both SMLP and IVR. Intravitreal ranibizumab group consisted of 24 patients who had undergone IVR monotherapy. Intravitreal ranibizumab therapy was one initial injection and on a pro re nata in both groups, and SMLP was performed at 1 month after IVR in the IVR + SMLP group. Preoperatively and monthly, best-corrected visual acuity and central retinal thickness were evaluated using swept source optical coherence tomography. Results: Best-corrected visual acuity and central retinal thickness significantly improved at 6 months in IVR + SMLP and IVR groups. Best-corrected visual acuity and central retinal thickness were not significantly different between the two groups at any time points. The number of IVR injections during initial 6 months in IVR group (2.3 ± 0.9) was significantly greater (P = 0.034) than that in IVR + SMLP group (1.9 ± 0.8). Conclusion: The combination therapy of IVR and SMLP can treat branch retinal vein occlusion cystoid macular edema effectively, by decreasing the frequency of IVR injections while maintaining good visual acuity. RETINA 0:1–8, 2018<br />学位の種類: 博士（医学）. 報告番号: 乙第2237号. 学位記番号: 新大博（医）乙第1809号. 学位授与年月日: 平成31年3月15日<br />RETINA. 2019, 39(7), 1377–1384.<br />新大博（医）乙第1809号
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| 43.
学位論文(リポジトリ) |
学位
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Suda, Kazuaki
概要:
Endometriosis is characterized by ectopic endometrial- like epithelium and stroma, of which molecular characteristics re
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main to be fully elucidated. We sequenced 107 ovarian endometriotic and 82 normal uterine endometrial epithelium samples isolated by laser microdissection. In both endometriotic and normal epithelium samples, numerous somatic mutations were identified within genes frequently mutated in endometriosis-associated ovarian cancers. KRAS is frequently mutated in endometriotic epithelium, with a higher mutant allele frequency (MAF) accompanied by arm-level allelic imbalances. Analyses of MAF, combined with multiregional sequencing, illuminated spatiotemporal evolution of the endometriosis and uterine endometrium genomes. We sequenced 109 single endometrial glands and found that each gland carried distinct cancer-associated mutations, demonstrating the heterogeneity of the genomic architecture of endometrial epithelium. Remarkable increases in MAF of mutations in cancer-associated genes in endometriotic epithelium suggest retrograde flow of endometrial cells already harboring cancer-associatedmutations, with selective advantages at ectopic sites, leading to the development of endometriosis.<br />学位の種類: 博士（医学）. 報告番号: 甲第4519号. 学位記番号: 新大院博（医）甲第841号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第841号
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| 44.
学位論文(リポジトリ) |
学位
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Tanaka, Miho
概要:
Background: Hyperserotonemia in the brain is suspected to be an endophenotype of autism spectrum disorder(ASD). Reducing
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serotonin levels in the brain through modulation of serotonin transporter function may improve ASD symptoms. Methods: We analyzed behavior and gene expression to unveil the causal mechanism of ASD-relevant social deficits using serotonin transporter (Sert) knockout mice. Results: Social deficits were observed in both heterozygous knockout mice (HZ) and homozygous knockout mice (KO), but increases in general anxiety were only observed in KO mice. Two weeks of dietary restriction of the serotonin precursor tryptophan ameliorated both brain hyperserotonemia and ASD-relevant social deficits in Sert HZ and KO mice. The expression of rather distinct sets of genes was altered in Sert HZ and KO mice, and a substantial portion of these genes was also affected by tryptophan depletion. Tryptophan depletion in Sert HZ and KO mice was associated with alterations in the expression of genes involved in signal transduction pathways initiated by changes in extracellular serotonin or melatonin, a derivative of serotonin. Only expression of the AU015836 gene was altered in both Sert HZ and KO mice. AU015836 expression and ASD-relevant social deficits normalized after dietary tryptophan restriction. Conclusions: These findings reveal a Sert gene dose-dependent effect on brain hyperserotonemia and related behavioral sequelae in ASD and a possible therapeutic target to normalize brain hyperserotonemia and ASD-relevant social deficits. Keywords: Serotonin transporter, Tryptophan depletion, Autism spectrum disorder, Heterozygous mice<br />学位の種類: 博士（医学）. 報告番号: 甲第4520号. 学位記番号: 新大院博（医）甲第842号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第842号
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| 45.
学位論文(リポジトリ) |
学位
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Kawata, Yuzo
概要:
学位の種類: 博士（医学）. 報告番号: 甲第4521号. 学位記番号: 新大院博（医）甲第843号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第843号
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| 46.
学位論文(リポジトリ) |
学位
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Morita, Keisuke
概要:
The basal lamina of the villous epithelium in the small intestine has numerous fenestrations, which are produced by leuk
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ocytes for their intraepithelial migration. We previously showed that these fenestrations change due to the dynamics of migrating leukocytes in response to dietary conditions and suggested the possibility that this change is related to the regulation of the absorption of large nutrients such as chylomicrons. The present study was, thus, designed to investigate structural changes in basal lamina fenestrations in response to a high-fat diet. The ultrastructure of the intestinal villi in the rat upper jejunum was investigated by electron microscopy of tissue sections in both the normal and the high-fat diet groups, and the fenestrations in the villous epithelium of rat upper jejunum were studied by scanning electron microscopy of osmium macerated/ ultrasonicated tissues. The present study showed that free cells adhering to the fenestrations increased in the upper jejunum two hours after feeding high-fat diet and the area of the fenestrations in this region also increased after feeding high-fat diet for 2 days. This enlargement of fenestrations may play an important role in increasing the efficiency of lipid absorption by facilitating the movement of chylomicrons from the intercellular space to the lamina propria.<br />学位の種類: 博士（医学）. 報告番号: 甲第4522号. 学位記番号: 新大院博（医）甲第844号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第844号
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| 47.
学位論文(リポジトリ) |
学位
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Watanabe, Yusuke
概要:
We describe a novel therapeutic approach for cirrhosis using mesenchymal stem cells (MSCs) and colony-stimulating factor
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-1-induced bone marrow-derived macrophages (id-BMMs) and analyze the mechanisms underlying fibrosis improvement and regeneration. Mouse MSCs and id-BMMs were cultured from mouse bone marrow and their interactions analyzed in vitro. MSCs, id-BMMs, and a combination therapy using MSCs and id-BMMs were administered to mice with CCl_4-induced cirrhosis. Fibrosis regression, liver regeneration, and liver-migrating host cells were evaluated. Administered cell behavior was also tracked by intravital imaging. In coculture, MSCs induced switching of id-BMMs toward the M2 phenotype with high phagocytic activity. In vivo, the combination therapy reduced liver fibrosis (associated with increased matrix metalloproteinases expression), increased hepatocyte proliferation (associated with increased hepatocyte growth factor, vascular endothelial growth factor, and oncostatin M in the liver), and reduced blood levels of liver enzymes, more effectively than MSCs or id-BMMs monotherapy. Intravital imaging showed that after combination cell administration, a large number of id-BMMs, which phagocytosed hepatocyte debris and were retained in the liver for more than 7 days, along with a few MSCs, the majority of which were trapped in the lung, migrated to the fibrotic area in the liver. Host macrophages and neutrophils infiltrated after combination therapy and contributed to liver fibrosis regression and promoted regeneration along with administered cells. Indirect effector MSCs and direct effector id-BMMs synergistically improved cirrhosis along with host cells in mice. These studies pave the way for new treatments for cirrhosis. STEM CELLS TRANSLATIONAL MEDICINE 2018;00:1–14<br />学位の種類: 博士（医学）. 報告番号: 甲第4523号. 学位記番号: 新大院博（医）甲第845号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第845号
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| 48.
学位論文(リポジトリ) |
学位
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石黒, 敬信
概要:
学位の種類: 博士（医学）. 報告番号: 甲第4524号. 学位記番号: 新大院博（医）甲第846号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第846号
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| 49.
学位論文(リポジトリ) |
学位
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Kabata, Yudai
概要:
The touch domes of mammalian hairy skin are mechanoreceptors characterized by the accumulation of Merkel cell-neurite co
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mplexes at the epidermal base. In this study, we examined the shape, size, and density of the touch dome of human skin of the forearm and the abdomen through scanning electron microscopy (SEM). Human skin samples were obtained from donated bodies, as well as a patient who underwent biopsy. Skin pieces were treated with a KOH-collagenase method for the separation of the epidermis from the dermis. The basal surface of the separated epidermis was then observed using SEM. The touch dome was clearly determined as a concave area bordered by a thick epidermal ridge, where neural components accumulated. The touch dome was rather independent from hair follicles, although they were sometimes located beside the touch dome. The average size and density of the touch dome were 0.06 mm2 and 3.82 /cm2 in the forearm, and 0.10 mm2 and 1.30 /cm2 in the abdomen, respectively. Our results suggested that the regional difference in size and density of the touch dome might be related to the sensation's sensitivity as touch spots in human hairy skin.<br />学位の種類: 博士（医学）. 報告番号: 甲第4525号. 学位記番号: 新大院博（医）甲第847号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第847号
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| 50.
学位論文(リポジトリ) |
学位
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Kamimura, Kensuke
概要:
Adolescents and young adults (AYAs) with cancer often live long lives following treatment and face many life events. No
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detailed studies of cancers in AYAs have described the epidemiology, treatment outcome, and social status in Japan. The present study defined AYAs as those aged 15‑29 years old based on the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. Data was collected from the hospital‑based cancer registry and electronic medical charts at Niigata University Medical and Dental Hospital from 2007 to 2015. The present study analyzed the types of cancer, treatment methods and outcomes, fertility preservation, marital status, raising children, school admission, and employment status. A total of 362 (1.9%) cancer cases in AYAs (males 119, females 243) were identified. Carcinoma was the most common type of cancer in both sexes. Females had a high incidence of carcinoma of the genitourinary tract (28.0%). Fertility‑sparing surgery (16.0%) was the most common method of fertility preservation. The 5‑year survival was better in females (88.4%) than in males (79.9%). The percentage of married AYAs increased following cancer treatment. The proportion of unemployment increased following cancer treatment in all age groups and was greatest (12.6%) in those aged 20‑24 years old. Compared with SEER data from the United States, the incidence of carcinoma was high among AYAs, particularly genitourinary tract carcinomas in females, while the incidence of melanoma and skin carcinomas was low. Therefore, AYAs with cancer requires social and economic support.<br />学位の種類: 博士（医学）. 報告番号: 甲第4526号. 学位記番号: 新大院博（医）甲第848号. 学位授与年月日: 平成31年3月25日<br />新大院博（医）甲第848号
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