Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Idiopathic Retroperitoneal Hematoma with Spontaneous Resolution / 대한소화기학회지

A 54-year-old man was transferred from another hospital due to a hematoma in the third portion of the duodenum on abdomen CT. He had been admitted for 2 weeks due to vomiting at another hospital. He had abdominal discomfort and nausea without abdominal pain when he visited the Gwangyang Sarang Hospital. Other than a distended abdomen and mild general abdominal tenderness, the results of physical examination were unremarkable. Abdominal CT revealed an approximately 9 cm thick walled hematoma at the anteroinferior site of the duodenal third portion. Upper endoscopy revealed stenosis of the third portion of the duodenum without mucosal lesions. The endoscope was not advanced through the narrowed duodenal lumen. A retroperitoneal hematoma was diagnosed, and his state was classified as subacute rather than acute based on the duration. The surgeon did not recommend surgical treatment. Urgent treatment was unnecessary; he was managed conservatively. The size of the hematoma decreased from 9.0 cm to 5.8 cm on the following CT. He could begin to eat food on the 26th admission day, and he was discharged on the 31st admission day. The hematoma disappeared entirely on the following CT. This paper describes a rare case of idiopathic retroperitoneal hematoma with a spontaneous resolution.

Insulin-like Growth Factor-1 Receptor Dictates Beneficial Effects of Treadmill Training by Regulating Survival and Migration of Neural Stem Cell Grafts in the Injured Spinal Cord

Survival and migration of transplanted neural stem cells (NSCs) are prerequisites for therapeutic benefits in spinal cord injury. We have shown that survival of NSC grafts declines after transplantation into the injured spinal cord, and that combining treadmill training (TMT) enhances NSC survival via insulin-like growth factor-1 (IGF-1). Here, we aimed to obtain genetic evidence that IGF-1 signaling in the transplanted NSCs determines the beneficial effects of TMT. We transplanted NSCs heterozygous (+/−) for Igf1r, the gene encoding IGF-1 receptor, into the mouse spinal cord after injury, with or without combining TMT. We analyzed the influence of genotype and TMT on locomotor recovery and survival and migration of NSC grafts. In vitro experiments were performed to examine the potential roles of IGF-1 signaling in the migratory ability of NSCs. Mice receiving +/− NSC grafts showed impaired locomotor recovery compared with those receiving wild-type (+/+) NSCs. Locomotor improvement by TMT was more pronounced with +/+ grafts. Deficiency of one allele of Igf1r significantly reduced survival and migration of the transplanted NSCs. Although TMT did not significantly influence NSC survival, it substantially enhanced the extent of migration for only +/+ NSCs. Cultured neurospheres exhibited dynamic motility with cytoplasmic protrusions, which was regulated by IGF-1 signaling. IGF-1 signaling in transplanted NSCs may be essential in regulating their survival and migration. Furthermore, TMT may promote NSC graft-mediated locomotor recovery via activation of IGF-1 signaling in transplanted NSCs. Dynamic NSC motility via IGF-1 signaling may be the cellular basis for the TMT-induced enhancement of migration.

Electron Microscopic Autoradiographic Study on the Secretion of Atrial Specific Granules from Atrial Cardiocytes in Dehydrated Rats / 대한해부학회지

This study was performed to investigate for the effect of dehydration on the synthesis, secretion and secreted pathway of atrial specific granules contained ANP by electron microscopic autoradiography. Male Sprague-Dawley rats, body weigh of about 50 g (range 47 to 53 g), were divided into control, 1 day dehydration and 3 days dehydration groups. Each group was divided into four groups according to sacrificed time on 20 min, 60 min and 240 min after the injection of L-leucine 3 H. Tissues of the right atrium obtained from animals were processed for typical electron microscopic procedure, and then embedded in Epon 812. Ultrathin sections were followed for electron microscopic autoradiographic method. Atrial specific granules were various in size, and some granules had a lower electron densities and indistinct granular membrane in the dehydration groups compared with the control group. In the electron microscopic autoradiographs of atrial wall, silver grains indicated by means of the positions of labelled L-leucine 3 H over the cell inclusion included atrial specific granules, cell organelles, intercellular spaces and blood vesseles. In the control group, high specific radioactivity was observed in the Golgi apparatus at 20 min, and in the rough endoplasmic reticulums and atrial specific granules at 60 min after the injection of L-leucine3H. And high level of radioactivities were observed in the cell membranes and blood vesseles at 240 min after the injection of L-leucine3H. In the 1 day and 3 days dehydration groups, radioactivities of Golgi apparatus, atrial specific granules, cell membranes and intercellular spaces were high level at 20 min, and radioactivities of rough endoplasmic reticulums and blood vesseles were high level at 60 min after isotope injection. Stored atrial specific granules were increased to 34.1% in the 1 day dehydration group, 27.4% in the 3 days dehydration group compared with the control group. In the 3 days dehydration group, newly formed granules increased 85.02% at 20 min, but those decreased rapidly to 36.87% at 60 min, 20.45% at 240 min after the injection of L-leucine3H in atrial cardiocytes. This results suggest that total ANP increased rapidly in the atrial cardiocytes, and newly formed ANP secreted rapidly into the intercellular space in the condition of dehydration, and ANP from atrial cardiocytes remain in intercellular space for dehydration period.

Morphological Observations on the Changes of Membrane Permeability by Immobilization Stress in the Rat Atrial Myocyte / 대한해부학회지

This study was performed to investigate the effect of immobilization stress on the ultrastructural changes and membrane permeability in rat atrial myocyte using immunohistochemical and lanthanum tracer techniques. Male Sprague-Dawley rats, body weight 160~200 g, were used for all immobilization stress group. Rats were immobilized in small round plastic tube for 6, 12 or 24 hours, except for the control group. Alterations of myocardial myoglobin and alpha-actinin as well as membrane permeability after immobilization stress were examined by immunohistochemistry, and lanthanum permeability of the rat atrial myocyte were observed by electron microscopy. In the control group, there was no loss of myoglobin or alpha-actinin from the atrial myocytes. After 6 and 12 hours immobilization stress, the loss of myoglobin and alpha-actinin could be identified the atrial myocytes. In the 24 hour immobilization groups, the content of the myoglobin and alpha-actinin recovered partially. Lanthanum was deposited only in the intercellular space of the atrial myocardium in the control group. In the 6 hour immobilization group, the atrial myocytes showed severe ultrastructural changes during immobilization stress. Lanthanum deposited in the sarcoplasm, myofibrils, adjacent of mitochondria, and mitochondrial matrix. In the 12 or 24 hour immobilization groups, the morphological alteration of atrial myocytes appeared weekly. In the 12 hour group, lanthanum deposited in myofibrils, adjacent of mitochondria and in the mitochondrial matrix. In the 24 hour group, lanthanum deposited mainly in intercellular space of atrial myocardium, and rarely in the sarcoplasm of myocytes. These results suggest that the immobilization stress may induce the alteration of cardiac cell membrane permeability and the ultrastructures of atrial myocardium.

The Effects of Immobilization Stress on the Ultrastructure of Rat Atrial Myocytes / 체질인류학회지

This study was performed to investigate the subcellular changes of rat atrial muscle cells by immobilization stress. Sprague -Dawley rats weighting 200 gm were immobilized in small round plastic tube for 2, 6, 12, and 24 hours respectively. The atrial tissue obtained from each animals were observed by transmission electron microscopes. In the heart of rat subjected 2 hours immobilization stress no significant morphological changes were found in electron microscopy, similarly as in control animal. After 6 and 12 hours immobilization stress, the following electron -microscopic changes of atrial myocytes were observed at the swelling of mitochondrial matrix with disturbance in cristea, focal loss of cytoplasmic matrix, vacuoles with myeline -like structure, apoptotic changes of myocytes, focal widening of intercalated disc interspace and lysis of myofibrils. After 24 hours immobilization stress, very small sized mitochondria, similarly as small sized secretory granules and various sized granules are observed in the perinuclear region of atrial myocytes. Atrial specific granules are moved centripetally toward the central region of the atrial myocytes after immobilization stress. Above results will be aid in understanding the structures of atrium with dual function of blood circulation and endocrine, and in research of modulation of secretory granules in atrial muscle cells.

Combination Chemotherapy for Malignant Ovarian Germ Cell Tumors / 대한부인종양콜포스코피학회잡지

Thirteen patients with malignant germ cell tumars of the ovary have been treated with a combination chemotherapy. The age of the patients ranged from ll to 50 years and there was no history of radiation therapy of chemotherapy except operation, Stage distributions are as follow ; 2 pstients are stage IV, 3 are stage II and remainied 8 are stage I. 4 patients with immature teratama and 2 patients with mixed germ cell tumor received VAC chemotherapy, as primary therapy, and among them 1 lost to follow up but remained 5 cases live without evidence of disease 39 to 83 gnontha. There were 3 patients with endodermal sinus tumor and 1 received VAC and remeined 2 received FVB as primary chemotherapy, Of them 1 died of disease after 9 months of oyeration and the other 2 live now with no evidence of disease. There were 2 patiente with dysgerminoma and 2 with primary ovarian choriocarcinoma. 1 patient with dysagerminoma and 1 wit choriocarcinoma were died because of chemotherapy toxicity, 1 patient with dysgerminoma, who refused further ehemotherapy after l course of chemot.herapy, died of progressive disease. l patient wit choriocarcinoma now live well without evidence of disease at 35 months. The combination chemotherapy using VAC or PVB regimen represents an effective treatment for malignant. germ cell turnars of the ovary and reveals moderate oxicity.