Somatostatin induces hyperpolarization in pancreatic islet α cells by activating a G protein-gated K+ channel

AbstractSomatostatin inhibits glucagon-secretion from pancreatic α cells but its underlying mechanism is unknown. In mouse α cells, we found that somatostatin induced prominent hyperpolarization by activating a K+ channel, which was unaffected by tolbutamide but prevented by pre-treating the cells with pertussis toxin. The K+ channel was activated by intracellular GTP (with somatostatin), GTPγS or Gβγ subunits. It was thus identified as a G protein-gated K+ (KG) channel. RT-PCR and immunohistochemical analyses suggested the KG channel to be composed of Kir3.2c and Kir3.4. This study identified a novel ionic mechanism involved in somatostatin-inhibition of glucagon-secretion from pancreatic α cells

Comprehensive analysis of gene expression of isolated pancreatic islets during pretransplant culture

Background: The aim of this study was to investigate the effect of pretransplant culture on the survival of panThe aim of this study was to investigate the effect of pretransplant culture on the survival of pancreatic islet grafts, and to determine the biological characteristics of isolated islets during pretransplant culture. Methods: The survival of islets from Wistar rats, transplanted to diabetic C57BL/B6 mice, was compared between fresh islets and cultured islets. A comprehensive gene expression analysis was employed to investigate biological processes during pretransplant culture, and in vitro validation studies were performed. Results: Survival of cultured xenografts was significantly prolonged as compared to that of fresh islets (fresh:12.5 ± 1.9 days, 1-day cultured:16.0 ± 1.3 days (p= 0.017), 3-day cultured:17.0 ± 2.6 days (p= 0.014)). Comprehensive gene expression analysis identified significant upregulation of annotated functions associated with inflammation in cultured groups. Six proinflammatory genes, including heme oxygenase 1 (HO-1) and IL-6, were significantly upregulated during culture. Validation studies revealed significantly higher levels of IL-6 in the supernatant of cultured islets and HO-1 in the cultured islets when compared with fresh islets. Conclusion: Transplantation of cultured islets induced significant but minimal prolongation of graft survival in xenogeneic combinations. Comprehensive analysis of gene expression in cultured islets showed biological processes associated with proinflammation during culture

Prognostic Impact of Hypoxia-Inducible miRNA-210

Objective. The aim of this study was to investigate the prognostic value of MicroRNA-210 (miR-210) expression in patients with non-small-cell lung cancer (NSCLC). Methods. We examined the miR-210 expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship between miR-210 expression and clinicopathological factors as well as histological subtype was statistically analyzed. Results. miR-210 expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found between miR-210 expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated that miR-210 expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma. Conclusions. We showed that miR-210 may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma

Report from IPITA-TTS opinion leaders meeting on the future of β-cell replacement

Peer reviewe

Right gastro-omental artery reconstruction after pancreaticoduodenectomy for subtotal esophagectomy and gastric pull-up

Introduction: There are no reports on vessel reconstruction of right gastro-omental artery deficits due to pancreatic tumor resection. Here, we describe successful arterial reconstruction using the middle colic artery in a patient who had undergone esophageal reconstruction with a gastric tube and whose right gastro-omental artery had been resected. Presentation of case: A 70-year-old man underwent subtotal esophagectomy and reconstructive surgery with a retrosternal gastric tube for esophageal cancer. A follow-up computed tomography (CT) scan revealed a tumor on the pancreatic head that was adjacent to the right gastro-omental artery. Pancreaticoduodenectomy (PD) was subsequently performed. The gastro-omental artery was resected along with the tumor, creating a 7-cm deficit. The anastomosis was performed between the right branch of the middle colic artery and the distal end of the right gastro-omental artery. No complications that involved blood flow to the reconstructed esophagus were postoperatively observed. Four months after surgery, the blood flow to the gastric tube was confirmed by a contrast CT scan. Discussion: We reconstructed the right gastro-omental artery using the middle colic artery, and not a vein graft, as that would have required vessel anastomosis at two locations. The middle colic artery branches on the posterior surface of the pancreas, which is located close to the right gastro-omental artery. Conclusion: The middle colic artery provides sufficient blood supply to the pulled-up gastric tube. PD can be performed even in patients who have undergone esophageal reconstruction

Achieving clinically optimal balance between accuracy and simplicity of a formula for manual use: Development of a simple formula for estimating liver graft weight with donor anthropometrics.

In developing a formula for manual use in clinical settings, simplicity is as important as accuracy. Whole-liver (WL) mass is often estimated using demographic and anthropometric information to calculate the standard liver volume or recommended graft volume in liver transplantation. Multiple formulas for estimating WL mass have been reported, including those with multiple independent variables. However, it is unknown whether multivariable models lead to clinically meaningful improvements in accuracy over univariable models. Our goal was to quantitatively define clinically meaningful improvements in accuracy, which justifies an additional independent variable, and to identify an estimation formula for WL graft weight that best balances accuracy and simplicity given the criterion. From the Japanese Liver Transplantation Society registry, which contains data on all liver transplant cases in Japan, 129 WL donor-graft pairs were extracted. Among the candidate models, those with the smallest cross-validation (CV) root-mean-square error (RMSE) were selected, penalizing model complexity by requiring more complex models to yield a ≥5% decrease in CV RMSE. The winning model by voting with random subsets was fitted to the entire dataset to obtain the final formula. External validity was assessed using CV. A simple univariable linear regression formula using body weight (BW) was obtained as follows: WL graft weight [g] = 14.8 × BW [kg] + 439.2. The CV RMSE (g) and coefficient of determination (R2) were 195.2 and 0.548, respectively. In summary, in the development of a simple formula for manually estimating WL weight using demographic and anthropometric variables, a clinically acceptable trade-off between accuracy and simplicity was quantitatively defined, and the best model was selected using this criterion. A univariable linear model using BW achieved a clinically optimal balance between simplicity and accuracy, while one using body surface area performed similarly

Successful Management of Crizotinib-Induced Neutropenia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Case Report

Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK) gene rearrangement, is generally well tolerated. In contrast, neutropenia induced by crizotinib is a commonly reported grade 3 or 4 adverse event. In such cases, interruption and dose reduction of crizotinib might be necessary for some patients with severe neutropenia. However, information concerning clinical experience and management of severe neutropenia is currently limited. In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described