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Early detection of anastomotic leakage after esophagectomy using drain amylase levels
浜松医科大学博士(医学)doctoral医学系研究科thesi
Plgrkt-deficient female mice caused by a 1-bp deletion of exon4 can maintain colonies through sufficient lactation
雑誌掲載タイトル:Successful lactation in Plgrkt-deficient female mice caused by a 1-bp deletion of exon4Plasminogen (Pg) activation on the cell surfaces is an important for various (patho) physiologic condition. Plg-RKT is a cell membrane protein that binds to Pg and promotes the activation on the cell surface by Pg activators. To evaluate the role of Plg-RKT in atherosclerosis, Plgrkt gene in Ldlr-/-/Apobec1-/- was modified using in vivo CRISPR/Cas9. Synthetic RNA for Plgrkt and Cas9 complex was electroporated into the fertilized eggs in the oviducts. Plgrkt deficient mice caused by a 1-bp deletion was established. In contrast to Plgrkt-/- mice developed by conventional method, this newly developed mice did not represent lactation failure and could maintain the pups until weanling. The major obvious difference between these lines is the area of gene modification. The conventionally developed mouse possesses about 10 kb deletion of Plgrkt, which might relate to the lactation failure. Lactation failure is one of the lethal phenotypes in mammals, and analyses of causative genes are especially important for dairy industries. Further genome-wide analyses with both Plgrkt-/- mice will be helpful to find out the uncertain causative genes for lactation failure.journal articl
Pre-administration of a carboxypeptidase inhibitor enhances plasminogen accumulation and thrombolysis after tPA infusion: Demonstration by real-time intravital imaging analysis of microthrombi in mice
浜松医科大学博士(光医工学)doctoral医学系研究科doctoral thesi
Therapeutic monitoring of adalimumab at non-trough levels in patients with inflammatory bowel disease
浜松医科大学博士(医学)doctoral医学系研究科Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). In this study, we clarified the correlation between ADA monitoring, including non-trough level, and real-world IBD clinical outcomes. This retrospective, observational, single-center study involved patients with ulcerative colitis (19) and Crohn’s disease (33) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4?14 days after ADA administration. The AAA positivity rate was 23.1% (12/52). ADA continuity was higher in AAA-negative patients than in AAA-positive patients (P=0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off of 9.2μg/mL was associated with ADA continuity. The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (P=0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of the serum ADA level was set to 11.1μg/mL. Under the combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level at 4-14 days after ADA administration was ≥9.2μg/mL. Furthermore, endoscopic remission can be expected with a serum ADA level of ≥11.1μg/mL. Overall, to predict clinical outcomes, it would be useful to measure the blood level of ADA regardless of the timing of the trough.doctoral thesi
A Case Report of Childhood Onset Incomplete Susac Syndrome
Susac症候群は自己免疫的機序により頭蓋内、内耳、網膜の微小血管に炎症を来し、脳症、難聴、視力障害を生じる稀な症候群である。Susac症候群の多くは20?40歳で発症する。2歳10か月と若年で発症した不全型Susac症候群の1例を経験したので報告する。2歳10か月時に失調症状が出現し、経過中に脳梁と大脳深部白質に散在する頭部MRIT2強調像高信号の病巣、左網膜血管の微小炎症を認めた。頭痛や四肢の痺れを反復し、8歳7か月時髄液蛋白上昇と頭部MRIで白質新規病変を認めた。本例では聴力低下を認めず、不全型Susac症候群と診断した。mPSLパルスとPSL内服で治療するも再燃した。シクロフォスファミドパルス、月1回の免疫グロブリン大量療法(IVIG)、ミコフェノール酸モフェチルを併用し、12か月間再燃なく経過している。Susac症候群は、診断を確実に行うとともに、約60%で後遺症を呈するため、十分な免疫抑制療法による再燃防止が必要である。journal articl