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Glaucoma Diagnostic Performance of Retinal Blood Flow Measurement With Doppler Optical Coherence Tomography （ドップラーOCTを用いた網膜血流測定による緑内障の診断能）
Full text link博士（医学）旭川医科大
SETD2 and miR-21 as therapeutic targets for NUT midline carcinoma （NUT midline carcinomaの新規治療におけるSETD2とmiR-21の検討）
Full text linkNuclear Protein in Testis (NUT) Midline Carcinoma (NMC) is a rare and highly aggressive tumor with the bromodomain containing 4 proteins (BRD4)-NUT (NUTM1) gene fusion. Few targeted therapies are available for NMC, and thus novel therapeutic targets are required. To the best of our knowledge, the present study was the first to report that SET domain-containing protein 2 (SETD2) deficiency and microRNA (miRNA/miR)-21 may serve as novel therapeutic targets for the treatment of NMC. First, Next-Generation Sequencing (NGS) identified a novel SETD2 mutation (p.Ser2382fs) in the NMC cell lines, HCC2429 and Ty82. Trimethylation of lysine 36 on histone H3 expression was depleted in the NMC cells, which was indicative of SETD2 loss. NMC cells were sensitive to the WEE1 G2 checkpoint kinase (WEE1) inhibitor, AZD1775, in the cancer cells with SETD2 deficiency. NMC cells that were resistant to Bromodomain and Extra-Terminal Motif (BET) inhibitors were next established, and these resistant cells were also sensitive to AZD1775. Subsequently, miRNA analysis revealed that miR-21 expression was increased in BET-inhibitor-resistant NMC cells. In addition, miR-21 regulated the proliferation of NMCs. The miR-21 inhibitor also suppressed the proliferation of BET-inhibitor-resistant cells. Additionally, a digital PCR assay was established to detect NUT gene rearrangements to identify patients with NMC. A total of 32 clinical samples were analyzed and one case of NMC was identified, in which the novel SETD2 mutation was detected. These data suggested that SETD2 loss and miR-21 may be therapeutic targets for treatment of NMC.博士（医学）旭川医科大
Retinal Blood Velocity Waveform Characteristics With Aging and Arterial Stiffening in Hypertensive and Normotensive Subject （高血圧患者と正常血圧患者における年齢と動脈硬化性変化に伴う網膜血流速度波形の特徴）
Full text link博士（医学）旭川医科大
Indirect decompression of the central lumbar spinal canal by means of simultaneous bilateral transforaminal lumbar interbody fusion for severe degenerative lumbar canal stenosis with 3 years minimum follow-up （重度変性脊柱管狭窄に対して同時左右経椎間孔椎体間固定術による正中脊柱管間節除圧、３年間以上経過観察）
Full text link博士（医学）旭川医科大
Left Atrial Volume Index as a Predictor for Large-Vessel Occlusion in Cardiogenic Cerebral Infarction: A Single Cohort Study （心原性脳主幹動脈閉塞の予測因子としての左房容積係数に関する単施設後方視的研究）
Full text link博士（医学）旭川医科大
Role of Tumor Necrosis Factor Receptor 1-Reactive Oxygen Species-Caspase 11 Pathway in Neuropathic Pain Madiated by HIV gp120 with Morphine in Rats （HIV gp120とモルヒネにより誘発された神経障害性疼痛モデルラットにおけるTNFR1－活性酸素腫－カスペース11経路の役割）
Full text link博士（医学）旭川医科大
Centrally administered orexin prevents lipopolysaccharide and colchicine induced lethality via the vagal cholinergic pathway in a sepsis model in rats （オレキシン中枢投与は，リポポリサッカライドとコルヒチンによるラット敗血症死をコリン作動性迷走神経路を介して改善する）
Full text linkOrexins are neuropeptides implicated in several physiological functions. Accumulating findings suggest a relationship between orexin and sepsis. A recent study demonstrated that orexin acts centrally to improve conditions in sepsis. The present study aims to clarify the precise mechanisms by which central orexin could induce a protective action against septic conditions. We established a new septic model by treating rats with lipopolysaccharide (LPS) and colchicine and used this to examine the effect of brain orexin on survival. Observation of survival was stopped three days after the chemicals injection or at death. We established a lethal model (rats died within 24 h) by injecting subcutaneously a combination of 1 mg/kg LPS and 1 mg/kg colchicine. A Toll-like receptor 4 (TLR4) inhibitor completely blocked lethality, suggesting a vital role of LPS-TLR4 signaling in the process. Intracisternal orexin-A dose-dependently reduced lethality in the sepsis model while neither intracisternal orexin-B nor intraperitoneal orexin-A changed the mortality rate. Vagal stimulation with carbachol or 2-deoxy-D-glucose improved survival and atropine potently blocked the protection by carbachol or 2-deoxy-D-glucose. The orexin-A-induced reduction of lethality was significantly blocked by atropine or surgical vagotomy. Intracisternal injection of an OX1 receptor antagonist blocked the improvement of survival by intracisternal injection of orexin-A, carbachol, or 2-deoxy-D-glucose. These results suggest that orexin acts centrally to reduce the lethality in our septic model treated (LPS and colchicine). Activation of the vagal cholinergic pathway may mediate the action of orexin, and the OX1 receptor in the brain might play a role in the process. Since the efferent vagus nerve mediates anti-inflammatory mechanisms, we speculate that the vagal cholinergic anti-inflammatory pathway is implicated in the mechanisms of septic lethality reduction by brain orexin.博士（医学）旭川医科大