Newly developed autoimmune cholangitis without relapse of autoimmune pancreatitis after discontinuing prednisolone.

A 57-year-old man presented with a 2-wk history of painless jaundice and weight loss. He had a large ill-defined enhancing mass-like lesion in the uncinate process of the pancreas with stricture of the distal common bile duct. Aspiration cytology of the pancreatic mass demonstrated inflammatory cells without evidence of malignancy. Total serum immunoglobulin G level was slightly elevated, but IgG4 level was normal. After the 2-wk 40 mg prednisolone trial, the patient's symptoms and bilirubin level improved significantly. A follow-up computed tomography (CT) scan showed a dramatic resolution of the pancreatic lesion. A low dose steroid was continued. After six months he self-discontinued prednisolone for 3 wk, and was presented with jaundice again. A CT scan showed newly developed intrahepatic biliary dilatation and marked concentric wall thickening of the common hepatic duct and the proximal common bile duct without pancreatic aggravation. The patient's IgG4 level was elevated to 2.51 g/L. Prednisolone was started again, after which his serum bilirubin level became normal and the thickening of the bile duct was resolved. This case suggests that autoimmune pancreatitis can progress to other organs that are not involved at the initial diagnosis, even with sustained pancreatic remission.

Duodenal obstruction following acute pancreatitis caused by a large duodenal diverticular bezoar.

Bezoars are concretions of indigestible materials in the gastrointestinal tract. It generally develops in patients with previous gastric surgery or patients with delayed gastric emptying. Cases of periampullary duodenal divericular bezoar are rare. Clinical manifestations by a bezoar vary from no symptom to acute abdominal syndrome depending on the location of the bezoar. Biliary obstruction or acute pancreatitis caused by a bezoar has been rarely reported. Small bowel obstruction by a bezoar is also rare, but it is a complication that requires surgery. This is a case of acute pancreatitis and subsequent duodenal obstruction caused by a large duodenal bezoar migrating from a periampullary diverticulum to the duodenal lumen, which mimicked pancreatic abscess or microperforation on abdominal computerized tomography. The patient underwent surgical removal of the bezoar and recovered completely.

Ectopic pancreas bleeding in the jejunum revealed by capsule endoscopy.

Ectopic pancreas is defined as pancreatic tissue found outside the usual anatomic location. It is often found incidentally at different sites in the gastrointestinal (GI) tract. The incidence of ectopic pancreatic tissue in autopsy series is 1% to 2%, with 70% of the ectopic lesions found in the stomach, duodenum and jejunum. Although it is usually a silent anomaly, an ectopic pancreas may become clinically evident when complicated by inflammation, bleeding, obstruction or malignant transformation. We report a case of ectopic pancreas located in the jejunum and presenting as an obscure GI bleeding, which was diagnosed by capsule endoscopy.

Mouse Melanoma Cell Migration is Dependent on Production of Reactive Oxygen Species under Normoxia Condition.

Cell migration plays a role in many physiological and pathological processes. Reactive oxygen species (ROS) produced in mammalian cells influence intracellular signaling processes which in turn regulate various biological activities. Here, we investigated whether melanoma cell migration could be controlled by ROS production under normoxia condition. Cell migration was measured by wound healing assay after scratching confluent monolayer of B16F10 mouse melanoma cells. Cell migration was enhanced over 12 h after scratching cells. In addition, we found that ROS production was increased by scratching cells. ERK phosphorylation was also increased by scratching cells but it was decreased by the treatment with ROS scavengers, N-acetylcysteine (NAC). Tumor cell migration was inhibited by the treatment with PD98059, ERK inhibitor, NAC or DPI, well-known ROS scavengers. Tumor cell growth as judged by succinate dehydrogenase activity was inhibited by NAC treatment. When mice were intraperitoneally administered with NAC, the intracellular ROS production was reduced in peripheral blood mononuclear cells. In addition, B16F10 tumor growth was significantly inhibited by in vivo treatment with NAC. Collectively, these findings suggest that tumor cell migration and growth could be controlled by ROS production and its downstream signaling pathways, in vitro and in vivo.

Actin-sequestering protein, thymosin beta-4, is a novel hypoxia responsive regulator.

Angiogenesis is induced by soluble factors such as vascular endothelial growth factor (VEGF) released from tumor cells in hypoxia. It enhances solid tumor growth and provides an ability to establish metastasis at peripheral sites by tumor cell migration. Thymosin beta-4 (TB4) is an actin-sequestering protein to control cytoskeletal reorganization. Here, we investigated whether angiogenesis and tumor metastasis are dependent on hypoxia conditioning-induced TB4 expression in B16F10 melanoma cells. TB4 expression in B16F10 cells was increased by hypoxia conditioning in a time-dependent manner. In addition, we found an increase of angiogenesis and HIF-1α expression in TB4-transgenic (Tg) mice as compared to wildtype mice. When wound healing assay was used to assess in vitro tumor cell migration, hypoxia conditioning for 1 h enhanced B16F10 cell migration. When TB4 expression in B16F10 cells was inhibited by the infection with small hairpin (sh) RNA of TB4 cloned in lentiviral vector, tumor cell migration was retarded. In addition, hypoxia conditioning-induced tumor cell migration was reduced by the infection of lentiviral shRNA of TB4. HIF-1α stabilization and the expression of VEGF isoform 165 and 121 in hypoxia were also reduced by the infection of lentiviral shRNA of TB4 in B16F10 cells. We also found an increase of tumor growth and lung metastasis count in TB4-Tg mice as compared to wildtype mice. Collectively, hypoxia conditioning induced tumor cell migration by TB4 expression-dependent HIF-1α stabilization. It suggests that TB4 could be a hypoxia responsive regulator to control tumor cell migration in angiogenesis and tumor metastasis.

Cooperation of actin-sequestering protein, thymosin ß-4 and hypoxia inducible factor-1α in tumor cell migration.

Cell migration plays an important role in many physiological and pathological processes, including tumor metastasis. Tumor cell migration is increased through the sequential induction of HIF-1α and VEGF under hypoxic conditions. Thymosin ß-4 (Tß4) is an actin-sequestering protein which controls cytoskeletal reorganization. Here, we investigated whether tumor cell migration could be co-operatively controlled by hypoxia and Tß4. Cell migration was measured by wound healing assay with scratching confluent monolayers of tumor cells. Cell migration was enhanced 18 h after scratching cells. In addition, we found that the expression of HIF-1α, VEGF-A isoform 164/120 and Tß4 was increased by scratching cells. Cell migration was decreased by the inhibition of Tß4 or HIF-1α expression with lentiviral shRNA of Tß4 or siRNA of HIF-1α, respectively. In contrast, cell migration was increased by the treatment with Tß4 proteins. The inhibitory effect of Tß4-shRNA or HIF-1α-siRNA was also attenuated by treatment with Tß4 proteins. Collectively, these findings suggest that Tß4 and HIF-1α cooperatively enhance tumor cell migration.

Complete fracture of sirolimus-eluting stent in a saphenous vein graft to left anterior descending artery.

Coronary stent fractures have been suggested as a potential new mechanism of restenosis. The mechanical properties of stents were designed not only to prevent vessel recoil, but also to resist the mechanical stress of vessel movement over millions of cardiac cycles. We present a case in which mechanical stress may have contributed to the fracture of a stent implanted in a saphenous vein graft (SVG) to the left coronary artery. The patient was admitted due to chest pain 2 years after receiving a coronary artery bypass graft. A coronary angiography revealed the culprit vessel to be the SVG to the left coronary artery. The graft was stenosed and was stented with a sirolimus-eluting stent. A 6-month follow-up coronary angiography revealed 80% in-stent restenosis with stent fracture. We re-intervened by balloon angioplasty. This is the first report of sirolimus-eluting stent fracture combined with restenosis of SVG in Korea.

Significance of inflammatory markers in diabetic patients with stable coronary artery disease.

BACKGROUND/AIMS: Patients with diabetes are prone to coronary artery disease (CAD); however, the majority of diabetic patients show normal coronary arteries. We examined differences in the clinical aspects of diabetic patients with insignificant and with significant stenosis of the coronary artery. METHODS: A total of 418 consecutive diabetic patients with stable angina who had undergone coronary angiography from January 2004 to March 2007 were included in this study. Patients were subdivided into control and CAD groups and then clinical characteristics and CAD-associated factors were evaluated. RESULTS: A total of 92 (22%) patients were assigned to the control group and 326 (78%) patients were assigned to the CAD group. Using univariate regression analysis, we found that patients with CAD were significantly older (control vs. CAD; 59+/-21 vs. 64.7+/-33.7, years, p<0.001), had a longer duration of diabetes (8.2+/-21.8 vs. 10.2+/-29.8, years, p=0.027), higher titers of high sensitivity C-reactive protein (hsCRP; 0.3+/-6.79 vs. 0.9+/-12.6, mg/dL, p=0.015), and increased hemoglobin A1c (HbA1c) levels (7.1+/-3.8 vs. 7.5+/-4.8, %, p=0.007) compared to control patients. Multivariate regression analysis showed that only differences in age, hsCRP, and HbA1c were statistically significant. When patients were subdivided into groups based on hsCRP levels (208 patients in the low group [49.8%], 210 patients in the high group [50.2%]), we found that patients with higher hsCRP levels showed more frequent multivessel disease. CONCLUSIONS: In diabetic patients, age, hsCRP, and HbA1c were associated with stable CAD. Among these factors, hsCRP levels were significantly correlated with multivessel involvement in diabetic CAD. Therefore, high hsCRP levels may be a strong predictor for atherosclerotic progression of the coronary arteries in diabetic patients, suggesting that regular screening tests should be performed.