Generation of Aberrant Transcripts of and Free DNA Ends in Zebrafish no tail Gene

Abstract The zebrafish no tail gene (ntl) is indispensable for the formation of the notochord and the tail structure. In a wild-type zebrafish population, we occasionally observed adult zebrafish with a narrow or no tailfin. This led us to examine the hypothesis that the activity of ntl was somehow genetically unstable. Here we present two findings regarding the gene. First, approximately 3% of ntl transcripts were aberrant; most of them carried deletions at various positions. Second, free, DNA double-stranded ends (DSEs) were formed at an AT dinucleotide repeat in ntl. DSEs were also generated in another zebrafish gene, noggin2 (nog2). DSEs in ntl and nog2 had common characteristics, which suggested that the AT repeats in these genes elicited DSEs by blocking progression of the replication

タンポウ ホゴテキ コヨウ ノ センクテキ キギョウ ニツイテ １９６０ネンダイ K シキ ノ ジッセン

荒川区南千住にあった(株)K機器は、福祉施策の整っていない1961年4月という早い時期から、精神遅滞者の保護的雇用を進め、民間企業としては異色の取組を行ってきた。その当時指導員を務めていた社長の娘さん、及び実際に就労していた方達からの聞き取り調査、更に文献資料によりその実態 ..

Duration of Postoperative Fever as a Simple and Useful Prognostic Indicator in Gastric Cancer Patients

[Background] Postoperative inflammation is associated with cancer progression in several cancers. However, the prognostic significance of postoperative fever remains unclear in gastric cancer patients. [Methods] We enrolled 442 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. [Results] The mean duration of postoperative fever ≥ 37°C was 8.7 days (range: 0–186 days) and significantly longer in patients with advanced gastric cancer, venous invasion, and open or total gastrectomy vs. patients with early gastric cancer (P = 0.0072), no venous invasion (P = 0.025), laparoscopic gastrectomy (P = 0.027), and either proximal or distal partial gastrectomy (P = 0.0015). Five-year overall survival rates were 69.5% vs. 83.6% in the prolonged postoperative fever group (≥ 6 days of ≥ 37°C) vs. the nonprolonged group (< 6 days of ≥ 37°C), respectively (P = 0.0008). In patients without Clavien-Dindo classification postoperative infectious complications grade ≥ 2, 5-year overall survival was 69.7% vs. 84.0% in patients with prolonged postoperative fever vs. those without, respectively (P = 0.0067). Five-year disease-specific survival was 85.9% vs. 93.1% in patients with prolonged fever vs. those without, respectively (P = 0.041). Multivariate analysis indicated that postoperative fever was an independent prognostic indicator. [Conclusion] Postoperative fever ≥ 37°C duration may be useful in predicting prognosis in gastric cancer patients

A Comparison of Gastric Cancer Surgery Between Japan and China

Background: The differences in gastric cancer between East and West have been frequently discussed. However, there are few studies that have compared Japan and China in Asia. Methods: Patient characteristics, surgical procedures and pathologic information were compared among gastric cancer patients who underwent curative-intent gastrectomy at two large volume cancer centers in China and Japan. Results: The median age of Japanese patients is 70 years, seven years older than those in China, and more than 25% of Japanese patients were older than 75. In China, the tumor was thicker, and lymph node metastasis was frequently observed. Total gastrectomy was more common in China (35.6% vs 21.9%). Distal gastrectomy rate was 56.0 percent in Japan, compared to 42.2 percent in China. The proportion of patients undergoing proximal gastrectomy was almost equal in China and Japan. Further analysis of the characteristics of patients undergoing total gastrectomy revealed that in China, more advanced gastric cancer patients with larger tumors and more lymph node metastasis underwent total gastrectomy, while in Japan, more early stage gastric cancer patients underwent total gastrectomy. Conclusion: There are some differences in gastric cancer between Japan and China. China needs to learn from Japan by establishing some screening programs for the diagnosis and treatment of early gastric cancer

P219L DAO alters ligand binding and catalytic efficiency

Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared to wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7-0.9 μM) compared to wild-type (1.2-2.0 μM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. The present study provides new insights into the structure-function relationship of human DAO

Comparisons of Postoperative Complications and Nutritional Status After Proximal Laparoscopic Gastrectomy with Esophagogastrostomy and Double-Tract Reconstruction

[Background] The purpose of this study was to compare postoperative complications and nutritional status between esophagogastrostomy and double-tract reconstruction in patients who underwent laparoscopic proximal gastrectomy, and assess the advantages of both surgical procedures. [Methods] Between 2010 and 2018, 47 cases underwent proximal gastrectomy with esophagogastrostomy (n = 23) or double-tract reconstruction (n = 24) at our institution for the treatment of clinical T1N0 adenocarcinoma located in the upper third of the stomach. Patient clinical characteristics, short-term outcomes, nutrition status, and skeletal muscle index were compared among the two groups. [Results] There was no significant difference between esophagogastrostomy and double-tract reconstruction in terms of operation time, blood loss, and length of postoperative hospital stay. Reflux symptoms and anastomotic stenosis were significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group (P < 0.001 and P = 0.004, respectively). There was no significant difference in anastomotic leakage, surgical site infection, and pancreatic fistula. For the nutritional status, the decrease rate of cholinesterase was significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group at 6 months (P = 0.008) There was no significant difference in the decrease rate of skeletal muscle mass index at 1 year after surgery. [Conclusion] Compared with esophagogastrostomy, double-tract reconstruction tends to have better short-term nutritional status and postoperative outcomes in terms of preventing the occurrence of gastroesophageal reflux and anastomosis stenosis. These findings suggest that double-tract reconstruction may be a useful method in laparoscopic proximal gastrectomy