Changes of lymphatic flow in case of pancreatic duct obstruction in the pig : as a model of pancreatic cancer

To investigate the lymph network change in pancreatic duct obstruction in pigs as a model of pancreatic cancer invading pancreatic duct, six domestic pigs weighing 17-40 kg underwent surgery as protocol. Two of them were controls, and the others underwent ligation of the pancreatic duct as a model of ductal obstruction. A CH 40 and lipiodol mixture was injected in their pancreas at 7 or 21 Days after first operation. Radiographic examination had been also performed. Five or 14 days later, they were examined radiographically, and sacrificed for histological examination. Ligation of the pancreatic duct caused experimental pancreatitis. Dilatation of the pancreatic duct and dilatation of the lymph canal in the interlobular space of pancreas was demonstrated in the ligation group. CH 40 and lipiodol showed discrepancies in the distribution. There were not distinct differences between the two groups in a route of CH 40 traveling. Only fluoroscopic examination revealed an image of lipiodol enlargement to the caudal site in the ligated group. The congestive lymph system may have impaired flow like reflux

Direct lymphatic spreading route into the liver from the gallbladder : an animal experiment using pig

In the special occasion that the physiological lymphatic flow is obstructed, gallbladder carcinoma (GBC)may spread into the liver via lymphatic route. Therefore, this study was conducted to find out the direct lymphatic route draining into the liver from the gallbladder using pigs with ligated cystic ducts. After injecting the carbon particle suspension (CH40) or the contrast medium (Lipiodol) into the subserosal layer of the gallbladder, the lymphatic route into the liver was examined both macroscopically and histologically. In controls, CH40 or Lipiodol drained along the cystic duct toward the hepatoduodenal ligament. After occlusion of cystic duct, CH40 was interrupted at the ligated point, and then spread into the liver nearby the gallbladder bed, running off to the liver hilus, toward the hepatoduodenal ligament. This route was confirmed by the Lipiodol drainage into the right median lobe of the liver, equivalent to the segments Vand IV a in humans. We presented for the first time the emergence of lymphatic drainage from the gallbladder into the liver after the occlusion of physiological lymphatic route using pigs. This implies that the direct spread into the segments Vand IVa of liver should be considered in the surgical treatment of advanced GBC

ISR-DEPENDENT METABOLIC REGULATION

The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation‐dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand‐activated skeletal muscle–specific derivative of the eIF2α protein kinase R‐like ER kinase revealed the expected up‐regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small‐molecule ISR activator that promoted Fgf21 expression in cell‐based screens and by implication of the ISR‐inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell‐autonomous proteostasis and amino acid metabolism, but also affects non‐cell‐autonomous metabolic regulation by induced expression of a potent myokine.—Miyake, M., Nomura, A., Ogura, A., Takehana, K., Kitahara, Y., Takahara, K., Tsugawa, K., Miyamoto, C., Miura, N., Sato, R., Kurahashi, K., Harding, H. P., Oyadomari, M., Ron, D., Oyadomari, S. Skeletal muscle‐specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21‐mediated non‐cell‐autonomous energy metabolism

A study of transileocolic vein obliteration (TIO) for gastric varices

Seven cases of giant gastric varices were treated using TIO combined with balloon occlusion of the gastro-renal shunt, for the purpose of reviewing the significance of TIO in the treatment of gastric varices. In 6 of the 7 cases, giant varices were cured completely. In the unsuccessful case, it was a giant varix (the minimum diameter was 25 mm or more) which had been failed to be treated by the TIO. In 3 of the 7 cases, the varices on the gastric fornix had ruptured ; therefore, emergency TIO was undertaken and resulted in successful hemostasis and disappearance of the varices. After treatment using this technique, one case developed esophageal varices, and two patients showed a reduction in esophageal varices. In case where gastric varices had been accompanied by RC sign-positive esophageal varices, favorable results were obtained with obliteration of the gastro-renal shunt was combined with compression of the esophagus which had served as another shunt in these cases. After TIO, hepatic function remained unchanged or improved slightly. No case showed exacerbation of hepatic function. For massive gastric varices with an inside diameter of up to 2 cm, transileocolic vein obliteration (TIO) combined with balloon occlusion of the gastro-renal shunt, which occludes the shunt in an anterograde manner, secures the occlusion of the shunt with no complications. This technique seems to be an effective therapy for gastric varices

Skeletal muscle–specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21–mediated non–cell-autonomous energy metabolism

The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation-dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand-activated skeletal muscle-specific derivative of the eIF2α protein kinase R-like ER kinase revealed the expected up-regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small-molecule ISR activator that promoted Fgf21 expression in cell-based screens and by implication of the ISR-inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine.Ministry of Education, Culture, Sports, Science and Culture (MEXT) of Japan Inoue Foundation for Science Mitsubishi Foundation Uehara Memorial Foundation Naito Foundation Cell Science Research Foundation Takeda Science Foundation Sankyo Foundation Ono Medical Research Foundation Mochida Memorial Foundation Ube Foundation Kowa Life Science Foundation Suzuken Memorial Foundation Kanae Foundation Japan Diabetes Foundation Japan Society for Promotion of Science (JSPS) EU FP7. Grant Number: 277713 Wellcome Trust. Grant Number: 084812/Z/08/

Skeletal muscle‐specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21‐mediated non‐cell‐autonomous energy metabolism

The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation-dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand-activated skeletal muscle-specific derivative of the eIF2α protein kinase R-like ER kinase revealed the expected up-regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small-molecule ISR activator that promoted Fgf21 expression in cell-based screens and by implication of the ISR-inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine.Ministry of Education, Culture, Sports, Science and Culture (MEXT) of Japan Inoue Foundation for Science Mitsubishi Foundation Uehara Memorial Foundation Naito Foundation Cell Science Research Foundation Takeda Science Foundation Sankyo Foundation Ono Medical Research Foundation Mochida Memorial Foundation Ube Foundation Kowa Life Science Foundation Suzuken Memorial Foundation Kanae Foundation Japan Diabetes Foundation Japan Society for Promotion of Science (JSPS) EU FP7. Grant Number: 277713 Wellcome Trust. Grant Number: 084812/Z/08/