Application of the Pseudo Global Warming Dynamic Downscaling Method to the Tokai Heavy Rain in 2000

The Tokai region in central Japan often receives heavy rainfall because of typhoons. Furthermore, because of global warming, the intensity of heavy rainfall events is expected to increase in the future. Therefore, assessment of possible differences in such events between the present and future is important. In this study, a record heavy rainfall event in the Tokai region on 11 September 2000, the so-called Tokai Heavy Rain (THR), was numerically simulated by weather research and forecasting model with triple nesting grid system of 50-, 10-, and 2-km horizontal resolution. Simulated results present characteristics of rainfall and atmospheric conditions similar to the actual event. Thus, the simulation is considered valid for reproducing rainfall processes of the THR. In addition, variations of heavy rainfall events in future climate scenarios are investigated using numerical simulations based on pseudo global warming (PGW) conditions, constructed using third-phase results of Coupled Model Intercomparison Project multi-model global warming experiments. Under certain future climate scenarios, the Tokai region may experience heavy rainfall events in which maximum hourly rainfall and extent of heavy rainfall areas increases. Such variations are mainly attributed to increased specific humidity in the lower troposphere. In some PGW runs, there was no significant rainfall around the Tokai region. There was increased specific humidity in these runs, and the horizontal distribution of lower atmospheric air temperature was favorable for the formation of a mesoscale convergence zone, as seen in PGW runs with heavy rainfall. However, vertical profiles of equivalent potential temperature and saturated equivalent potential temperature showed unsaturated and stable atmospheric stratifications that are unfavorable for convective activity. Even in cases with increased atmospheric temperature and specific humidity caused by global warming, differences in their spatial distributions and vertical profiles could lead to contrasting effects of global warming on a specific extreme weather event

Evaluation of Blood Supply with Indocyanine Green Fluorescence in Resection for Concurrent Gastric and Pancreatic Cancer: A Case Report

We present a rare case of concurrent resection of pancreatic and gastric cancer in which indocyanine green (ICG) fluorescence was used to evaluate the remnant stomach. An 80-year-old man was referred with a tumor in the distal pancreas. Computed tomography showed a 25-mm mass in the pancreatic tail; endoscopic ultrasound-guided fine-needle aspiration revealed adenocarcinoma. Upper gastrointestinal endoscopy and subsequent upper gastrointestinal series revealed advanced gastric cancer in the mid-stomach. Concurrent resection of the pancreatic and gastric tumors was performed. After distal pancreatectomy and distal gastrectomy, ICG evaluation of the stomach showed fluorescence extending only 3 cm distal from the cardia. To avoid ischemic change at the remnant stomach, total gastrectomy was performed. Since remnant gastric necrosis and anastomotic leak following ischemia can lead to fatal outcomes, the use of ICG to evaluate blood supply at anastomotic sites can help determine the extent of safe resection in such cases

Rho-ROCK Expression Predicts the Prognosis in Patients with T3/T4 Gastric Cancer

A small GTPase Rho protein and an effector ROCK have significant roles in cancer adhsion, metastasis, invasion, angiogenesis and cell mortality. We investigated the expressions of RhoA protein and ROCK-1 protein in 100 patients with macroscopically T3/T4 gastric cancer immunohistochemically. The expression of RhoA was detected in gastric cancer specimens from 39 patients and that of ROCK-1 in specimens from 30 patients. The clinicopathological characteristics of 21 tumors with co-expression of RhoA and ROCK-1 proteins (Rho/ROCK ON) were compared with those of the 79 remaining tumors (Rho/ROCK OFF). The percentage of lymph node metastasis positive cases in the Rho/ROCK ON group (81%) was higher than that in the Rho/ROCK OFF group (66%), but the difference was not significant (P = 0.183). However, the prognosis of the 21 patients with Rho/ROCK ON was significantly poorer than that of the 79 with Rho/ROCK OFF (P = 0.006). Our results indicate that the evaluation of the protein expression of RhoA and ROCK-1 is useful for predicting the prognosis in patients with T3/T4 gastric cancer

サイトカイン誘発好中球化学誘引物質の発現はTNFα発現を抑制することにより卵胞の閉鎖およびアポトーシスから回避させる

Aim: Cytokine-induced neutrophil chemoattractant (CINC/gro) is a CXC family chemokine, similar to interleukin-8 in rats, and is one of the factors that regulates ovulation. However, the mechanism that regulates atresia of the ovaries postovulation is not clearly defined. Methods: Whether antibody-blocking of CINC/gro can alter the number of ovulated oocytes and modulate neutrophil infiltration was investigated. The effect of the antibody on the level of inflammatory cytokine production and follicular atresia was examined. Apoptosis was measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and via analysis of the messenger RNA expression of Bcl-2 and Bcl2-associated X (Bax). Results: The anti-CINC/gro antibody treatment decreased the number of ovulated oocytes. The messenger RNA levels of cyclooxygenase-2 and interleukin-1 beta were decreased by the antibody treatment, whereas that of tumor necrosis factor (TNF) alpha was increased. The TUNEL analysis revealed a larger number of apoptotic cells in the antibody group, compared with those in the control group, as well as a significant increase in the Bax/Bcl-2 ratio 24 hours after human chorionic gonadotropin administration. Conclusion: These findings suggest that ovulation is accelerated by neutrophil infiltration into the theca layer. The CINC/gro appears to synergize with interleukin-1 beta for ovulation. By contrast, the data suggest that CINC/gro expression suppresses TNF alpha expression and that CINC/gro expression therefore prevents the follicles from undergoing atresia and apoptosis

The PI3K-Akt Pathway in SN-38-Induced Apoptosis in Human Gastric Cancer Cell Lines

SN-38, an active metabolite of a topoisomerase I inhibitor, CPT-11, exhibits a cytotoxic effect by inducing apoptosis in cancer cells. Phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling is known to protect a variety of cells from apoptosis. The relationship between resistance to SN-38-induced apoptosis and the PI3K-Akt pathway in human gastric cancer cells is unknown. Here, we did an investigation using two gastric cancer cell lines, MKN1 and MKN45. Cell viability was determined by sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) assay. Apoptosis was confirmed by fluorescence microscopy using Hoechst 33342 staining. Expression levels of phospho-Akt (pAkt) were determined by Western blotting. After being treated with SN-38, the populations of sub-G1 cells were induced by flow cytometry in 36.8% of MKN45 cells more frequently than in 13.5% of MKN1 cells. SN-38 inhibited the expression of pAkt dose-dependently in MKN45 cells, but not in MKN1 cells. In MKN1 cells, an additional pretreatment with the PI3K inhibitor, LY294002, led to the inhibition of pAkt expression and induced apoptosis. The results suggested that SN-38 induces apoptosis by decreasing PI3K-Akt survival signaling, the anti-apoptotic signals, in human gastric cancer cells. Akt inhibitor might be a useful anti-tumor agent in combination with CPT-11

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy

none67si: Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. We demonstrated that the LIG3 gene defects affect mtDNA maintenance, leading to mtDNA depletion without the accumulation of multiple deletions as observed in other mitochondrial disorders. This mitochondrial dysfunction is likely to cause the phenotypes observed in these patients. The most prominent and consistent clinical signs were severe gut dysmotility and neurological abnormalities, including leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder. A decrease in the number of myenteric neurons, and increased fibrosis and elastin levels were the most prominent changes in the gut. Cytochrome c oxidase (COX) deficient fibres in skeletal muscle were also observed. Disruption of lig3 in zebrafish reproduced the brain alterations and impaired gut transit in vivo. In conclusion, we identified variants in the LIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities.This work was supported by Telethon Grant GGP15171 to E.B. and R.D.G. and by a donation from Kobe city to the Department of General Pediatrics, Kobe University Graduate School of Medicine (K550003302). S.C. was supported by a Dutch Cancer Foundation grant (KWF11011). V.C. and A.M. were supported by the Italian Ministry of Health (“Ricerca Corrente” funding). R.D.G. is the recipient of grants from University of Ferrara (FAR and FIR funds).openBonora, Elena; Chakrabarty, Sanjiban; Kellaris, Georgios; Tsutsumi, Makiko; Bianco, Francesca; Bergamini, Christian; Ullah, Farid; Isidori, Federica; Liparulo, Irene; Diquigiovanni, Chiara; Masin, Luca; Rizzardi, Nicola; Cratere, Mariapia Giuditta; Boschetti, Elisa; Papa, Valentina; Maresca, Alessandra; Cenacchi, Giovanna; Casadio, Rita; Martelli, Pierluigi; Matera, Ivana; Ceccherini, Isabella; Fato, Romana; Raiola, Giuseppe; Arrigo, Serena; Signa, Sara; Sementa, Angela Rita; Severino, Mariasavina; Striano, Pasquale; Fiorillo, Chiara; Goto, Tsuyoshi; Uchino, Shumpei; Oyazato, Yoshinobu; Nakamura, Hisayoshi; Mishra, Sushil K; Yeh, Yu-Sheng; Kato, Takema; Nozu, Kandai; Tanboon, Jantima; Morioka, Ichiro; Nishino, Ichizo; Toda, Tatsushi; Goto, Yu-Ichi; Ohtake, Akira; Kosaki, Kenjiro; Yamaguchi, Yoshiki; Nonaka, Ikuya; Iijima, Kazumoto; Mimaki, Masakazu; Kurahashi, Hiroki; Raams, Anja; MacInnes, Alyson; Alders, Mariel; Engelen, Marc; Linthorst, Gabor; de Koning, Tom; den Dunnen, Wilfred; Dijkstra, Gerard; van Spaendonck, Karin; van Gent, Dik C; Aronica, Eleonora M; Picco, Paolo; Carelli, Valerio; Seri, Marco; Katsanis, Nicholas; Duijkers, Floor A M; Taniguchi-Ikeda, Mariko; De Giorgio, RobertoBonora, Elena; Chakrabarty, Sanjiban; Kellaris, Georgios; Tsutsumi, Makiko; Bianco, Francesca; Bergamini, Christian; Ullah, Farid; Isidori, Federica; Liparulo, Irene; Diquigiovanni, Chiara; Masin, Luca; Rizzardi, Nicola; Cratere, Mariapia Giuditta; Boschetti, Elisa; Papa, Valentina; Maresca, Alessandra; Cenacchi, Giovanna; Casadio, Rita; Martelli, Pierluigi; Matera, Ivana; Ceccherini, Isabella; Fato, Romana; Raiola, Giuseppe; Arrigo, Serena; Signa, Sara; Sementa, Angela Rita; Severino, Mariasavina; Striano, Pasquale; Fiorillo, Chiara; Goto, Tsuyoshi; Uchino, Shumpei; Oyazato, Yoshinobu; Nakamura, Hisayoshi; Mishra, Sushil K; Yeh, Yu-Sheng; Kato, Takema; Nozu, Kandai; Tanboon, Jantima; Morioka, Ichiro; Nishino, Ichizo; Toda, Tatsushi; Goto, Yu-Ichi; Ohtake, Akira; Kosaki, Kenjiro; Yamaguchi, Yoshiki; Nonaka, Ikuya; Iijima, Kazumoto; Mimaki, Masakazu; Kurahashi, Hiroki; Raams, Anja; MacInnes, Alyson; Alders, Mariel; Engelen, Marc; Linthorst, Gabor; de Koning, Tom; den Dunnen, Wilfred; Dijkstra, Gerard; van Spaendonck, Karin; van Gent, Dik C; Aronica, Eleonora M; Picco, Paolo; Carelli, Valerio; Seri, Marco; Katsanis, Nicholas; Duijkers, Floor A M; Taniguchi-Ikeda, Mariko; De Giorgio, Robert