Thioredoxin-1 maintains mechanistic target of rapamycin (mTOR) function during oxidative stress in cardiomyocytes

Thioredoxin 1 (Trx1) is a 12-kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism, and survival. We have shown previously that mTOR activity is increased in response to myocardial ischemia-reperfusion injury. However, whether Trx1 interacts with mTOR to preserve heart function remains unknown. Using a substrate-trapping mutant of Trx1 (Trx1C35S), we show here that mTOR is a direct interacting partner of Trx1 in the heart. In response to H2O2 treatment in cardiomyocytes, mTOR exhibited a high molecular weight shift in non-reducing SDS-PAGE in a 2-mercaptoethanol-sensitive manner, suggesting that mTOR is oxidized and forms disulfide bonds with itself or other proteins. The mTOR oxidation was accompanied by reduced phosphorylation of endogenous substrates, such as S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1) in cardiomyocytes. Immune complex kinase assays disclosed that H2O2 treatment diminished mTOR kinase activity, indicating that mTOR is inhibited by oxidation. Of note, Trx1 overexpression attenuated both H2O2-mediated mTOR oxidation and inhibition, whereas Trx1 knockdown increased mTOR oxidation and inhibition. Moreover, Trx1 normalized H2O2-induced down-regulation of metabolic genes and stimulation of cell death, and an mTOR inhibitor abolished Trx1-mediated rescue of gene expression. H2O2-induced oxidation and inhibition of mTOR were attenuated when Cys-1483 of mTOR was mutated to phenylalanine. These results suggest that Trx1 protects cardiomyocytes against stress by reducing mTOR at Cys-1483, thereby preserving the activity of mTOR and inhibiting cell death

A Case of Endoscopic Mucosal Resection of Carcinoma in Adenoma at the Minor Duodenal Papilla

Here, we describe a case of minor papillary adenocarcinoma in adenoma that was treated with endoscopic mucosal resection (EMR). In a 67-year-old woman, sigmoid colon cancer was incidentally detected on preoperative upper gastrointestinal endoscopy. Endoscopy revealed a slightly elevated lesion at the minor duodenal papilla. The findings of a histopathologic examination were suggestive of adenocarcinoma. Computed tomography and magnetic resonance images identified a minute tumor, whereas endoscopic ultrasonography revealed that the tumor did not spread to the pancreas. We performed EMR of this lesion. There were no complications, and relapse has not occurred in 3 years. Cases of minor papillary adenocarcinoma treated with EMR are quite rare

In vitro expansion of CD34+CD38- cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia

advance online publication, August 8, 2014 [Epub ahead of print]ArticleLEUKEMIA. 29(3):606-614 (2015)journal articl

脾動脈瘤３例の検討

今回当科で経験した脾動脈瘤３例について報告する．年齢は17歳から76歳（平均49.3歳）で、女性；１例、男性；２例であった．１例は破裂症例で緊急開腹，それ以外の２例は血管内治療を施行し,全て術後経過は良好であった．緊急開腹術を行った１例は２cm 未満の嚢状瘤であり，術前瘤径にとらわれず治療適応を考える必要がある．治療の第一選択として低侵襲な血管内治療を考慮する必要がある．We report 3 cases of splenic artery aneurysm (2 males,1 female; median age, 49.3 years; age range, 17-76 years).We performed splenectomy (included aneurysm) in emergency surgery for one ruptured case and performed endovascular therapy for two unruptured cases. The postoperative progress of all cases was satisfactory.Emergency case was saccular aneurysm under 2cm of size. Indication for treatment of intraabdominal aneurysm may be considered even in small size of aneurysm.All cases are still alive. It is necessary to take into account minimally invasive endovascular therapy in first-line

Gastric function preserving esophagectomy for esophageal cancer

Although, the gastric roll is widely used for reconstruction after an esophagectomy for esophageal cancer, adverse effects such as the post operative disturbance of oral intake and the reflux of gastric juice have been reported. A function preserving surgical procedure, which is similar to that for stomach and colon cancer, has been developed for esophageal cancer. Gastric function can be preserved by using the intestine as the reconstructive organ after an esophagectomy. In this report, we described the procedure for an esophagectomy with pedunculated jejunal or right colonic interposition, collectively termed as a gastric function preserving esophagectomy (GPE). We believe that this procedure is minimally invasive with a low risk of postoperative digestive symptoms and weight loss

Amino acid signaling in the intestine : The roles of glutamine, leucine and arginine

Amino acids have an influence on the function of organs, glands, tendons and arteries. Some of them play crucial roles in the control of gene expression by controlling the initiation phase of mRNA translation. Furthermore, recent studies have revealed that some kinds of amino acids directly participate in important signal transduction in the immune system. Glutamine, leucine and arginine play crucial roles in intestinal growth, integrity, and function through cellular signaling mechanisms. In this paper, we review amino acid signal transduction in the intestinal function

A case report of isolated presacral squamous cell carcinoma developed four years after gastrectomy

Chemoradiation therapy and a transsacral resection were performed to treat isolated squamous cell carsinoma that occurred in presacral tissues in the pelvis four years after gastrectomy due to early gastric cancer, with the prognosis continuing to be favorable. The patient was a 57-year-old woman, who came to our hospital having symptoms of anemia four years after gastrectomy. After a rectal examination, a tumor mass the size of a sparrowegg was discovered on the left rectal wall. An abdominal CT showed a tumor, 3.7cm × 3.7cm in size, on the outer left wall of the upper rectum. After a CT-guided biopsy, squamous cell carcinoma was detected. Irradiation (total 40 Gy) and chemotherapy (MMC+5-FU) were performed, mass shrinkage was confirmed, and a transsacral tumor resection was performed. According to the histopathological examination, a very small but viable cancer was found to be remaining. 4 years after the tumor removal, no recurrence has been discovered. Squamous cell carcinoma in the pelvis often originates from the vagina. However, the patient didn\u27t have any malignant findings from a genital examination at the time the symptoms appeared, and this case was diagnosed as isolated squamous cell carcinoma. A transsacral approach to remove such a tumor is considered to be useful because it is relatively low invasion and preserves anal functions