Transformation of peptide nanotubes into a vesicle via fusion driven by stereo-complex formation.

Two types of peptide nanotubes, one is prepared from an amphiphilic peptide having a right-handed helix segment and the other from that having a left-handed helix segment, are shown to transform the morphology into a vesicle by membrane fusion due to stereo-complex formation between these helical segments

Poorly Differentiated Adenocarcinoma with Signet-ring Cell Carcinoma of the Extrahepatic Bile Duct in a 42-year-old Japanese Female: A Case Report

Poorly differentiated adenocarcinoma without papilla or tubule formation of the extrahepatic bile duct is rare. Here we present a case (a 42-year-old Japanese woman) without either pancreatobiliary maljunction or liver disease. The patient had obstructive jaundice. Imaging studies revealed a bile duct tumor obstructing the common bile duct and invading the surrounding tissues. Pathologic examination revealed a dense periductal growth of poorly differentiated adenocarcinoma containing signet-ring cells, but without papilla or tubule formation in the extrahepatic bile duct. The tumor cells directly invaded the pancreatic parenchyma and the portal vein. In the extrahepatic bile duct, poorly differentiated adenocarcinoma may be established as a distinct clinicopathologic entity if the tumors are characterized by:1) the absence of papilla or tubule formation, 2) Asian preponderance, 3) occurrence at a younger age than is usual for patients with biliary cancers, and 4) an aggressive mural invasiveness.</p

Transient Effectiveness of an Oral 5-Fluorouracil Derivative, S-1, for Epirubicin, Cyclophosphamide and Paclitaxel Refractory Skin Metastases from Possible Occult Breast Cancer in a Male

Recent chemotherapies for skin metastases from breast cancer have shown to be effective for regression, disappearance, and favorable quality of life. We describe the case of a 76-year-old male showing transient effectiveness with an oral 5-fluorouracil derivative, S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate), for epirubicin, cyclophosphamide and paclitaxel refractory skin metastases from possible occult breast cancer. The male patient was initially diagnosed as having lymph node metastases in the left axilla as possible occult breast cancer. The skin metastases developed after chemotherapy with a combination of epirubicin and cyclophosphamide, subsequent chemotherapy with paclitaxel, and radiotherapy. Chemotherapy with paclitaxel was resumed for skin metastases, but it was not effective. Alternative chemotherapy with the oral agent S-1 was administered. The skin metastases completely disappeared after the second course, but recurred at the end of the third course. This case suggests that S-1 may be a candidate for chemotherapy for skin metastases from occult breast cancer in males

肺外科手術における術後早期の高次脳機能および術中脳酸素需給バランスに対する麻酔薬の効果 : ランダム化比較試験

PURPOSE: One-lung ventilation (OLV) may impair cerebral oxygen balance and induce postoperative cognitive dysfunction (POCD). It is unclear whether the type of anesthetic influences the incidence of POCD in patients undergoing OLV. This prospective study compared the incidence of POCD and intraoperative cerebral oxygen desaturation in OLV patients anesthetized with propofol vs sevoflurane during lung surgery. METHODS: There were 148 participants enrolled in this study and randomized equally to either the propofol or the sevoflurane group. Anesthesia was maintained with either propofol or sevoflurane combined in both groups with fentanyl and epidural anesthesia. Regional cerebral oxygen saturation (rSO2), jugular bulb venous oxygen saturation (SjO2), and the incidence of cerebral oxygen desaturation (rSO2 or SjO2 < 50% or rSO2 < 80% of baseline) were measured during anesthesia. Cognitive function was assessed using seven neurocognitive tests two days preoperatively, five days postoperatively (primary outcome), and three months postoperatively. Bivariable and multivariable regression analyses were conducted to identify factors associated with POCD. RESULTS: Rates of POCD did not differ statistically between groups five days postoperatively (propofol, 16/72 patients; sevoflurane, 24/72 patients; RR, 0.67; 95% CI, 0.39 to 1.15; P = 0.14) or three months postoperatively (propofol, 9/60 patients; sevoflurane, 12/58 patients; RR, 0.73; 95% CI, 0.33 to 1.59; P = 0.42). Only three subjects per group showed intraoperative cerebral oxygen desaturation. Multivariable regression analysis revealed older age as an independent predictor of POCD. CONCLUSIONS: No statistically significant difference in the incidence of POCD could be detected between the sevoflurane and propofol anesthesia groups. Postoperative cognitive dysfunction was relatively frequent following OLV in both groups. (REGISTRATION NUMBER: UMIN 000002826).博士（医学）・乙第1397号・平成29年3月15日© Canadian Anesthesiologists' Society 2016This is a post-peer-review, pre-copyedit version of an article published in Canadian journal of anaesthesia. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12630-016-0700-4

Slr0967 and Sll0939 induced by the SphR response regulator in Synechocystis sp. PCC 6803 are essential for growth under acid stress conditions

AbstractTwo-component signal transduction is the primary signaling mechanism for global regulation of the cellular response to environmental changes. We used DNA microarray analysis to identify genes that were upregulated by acid stress in the cyanobacterium Synechocystis sp. PCC 6803. Several of these genes may be response regulators that are directly involved in this type of stress response. We constructed deletion mutants for the response regulator genes and compared the growth rates of cells transfected with mutant and wild-type genes in a low pH medium. Of these mutants, deletion of sphR affected the growth rate under acid stress (pH 6.0) conditions. We examined genome-wide expression in ΔsphR mutant cells using DNA microarray to determine whether SphR was involved in the regulation of other acid stress responsive genes. Microarray and real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses of wild-type cells showed that the expression of phoA, pstS1, and pstS2, which are upregulated under phosphate-limiting conditions, increased (2.48-, 1.88-, and 5.07-fold, respectively) after acid stress treatment for 0.5h. In contrast, pstS2 expression did not increase in the ΔsphR mutant cells after acid stress, whereas the phoA and sphX mRNA levels increased. Furthermore, qRT-PCR and northern blot analysis indicated that downregulation of the acid-responsive genes slr0967 and sll0939 occurred with the deletion of sphR. Indeed, mutants of these genes were more sensitive to acid stress than the wild-type cells. Thus, induction of Slr0967 and Sll0939 by SphR may be essential for growth under acid stress conditions. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial

Distinctive detection of insulinoma using [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT

Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [¹⁸F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53R172H;Rbf/f mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [¹⁸F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma

Feasibility study of two schedules of sunitinib in combination with pemetrexed in patients with advanced solid tumors

Background Sunitinib is an oral multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, as well as of other receptor types. We have performed a feasibility study to investigate the safety of sunitinib in combination with pemetrexed for treatment of advanced refractory solid tumors. Methods Sunitinib was administered once daily on a continuous daily dosing (CDD) schedule (37.5 mg/day) or a 2-weeks-on, 1-week-off treatment schedule (50 mg/day, Schedule 2/1) in combination with pemetrexed at 500 mg/m2 on day 1 of repeated 21-day cycles. Results Twelve patients were enrolled in the study: six on the CDD schedule and six on Schedule 2/1. None of the treated patients experienced a dose-limiting toxicity. Toxicities were manageable and similar in type to those observed in monotherapy studies of sunitinib and pemetrexed. Pharmacokinetic analysis did not reveal any substantial drug–drug interaction. One patient with squamous cell lung cancer showed a partial response and five patients had stable disease. Conclusions Combination therapy with sunitinib administered on Schedule 2/1 (50 mg/day) or a CDD schedule (37.5 mg/day) together with standard-dose pemetrexed (500 mg/m2) was well tolerated in previously treated patients with advanced solid tumors