1.Hypoxia Increases β-Cell Death by Activating Pancreatic Stellate Cells within the Islet
Jong Jin KIM ; Esder LEE ; Gyeong Ryul RYU ; Seung-Hyun KO ; Yu-Bae AHN ; Ki-Ho SONG
Diabetes & Metabolism Journal 2020;44(6):919-927
Hypoxia can occur in pancreatic islets in type 2 diabetes mellitus. Pancreatic stellate cells (PSCs) are activated during hypoxia. Here we aimed to investigate whether PSCs within the islet are also activated in hypoxia, causing β-cell injury. Islet and primary PSCs were isolated from Sprague Dawley rats, and cultured in normoxia (21% O2) or hypoxia (1% O2). The expression of α-smooth muscle actin (α-SMA), as measured by immunostaining and Western blotting, was used as a marker of PSC activation. Conditioned media (hypoxia-CM) were obtained from PSCs cultured in hypoxia. Islets and PSCs cultured in hypoxia exhibited higher expressions of α-SMA than did those cultured in normoxia. Hypoxia increased the production of reactive oxygen species. The addition of N-acetyl-L-cysteine, an antioxidant, attenuated the hypoxia-induced PSC activation in islets and PSCs. Islets cultured in hypoxia-CM showed a decrease in cell viability and an increase in apoptosis. PSCs within the islet are activated in hypoxia through oxidative stress and promote islet cell death, suggesting that hypoxia-induced PSC activation may contribute to β-cell loss in type 2 diabetes mellitus.
2.Clinical Experience of Hyperfibrosis Occurred after Silicone Implant Insertion.
Yong Ah RYU ; Hyung Soo KIM ; Ki Ho LEE ; Seung Ryul LEE ; Nak Heon KANG
Journal of the Korean Cleft Palate-Craniofacial Association 2004;5(2):137-140
Facial depression is not rare conditions caused by soft tissue loss or bone distortion. In such conditions, autogenous bone, cartilage and bioacceptible materials are used for soft tissue augmentation. De Nicola used silicone rubber implant first in 1950. That after, silicone implants are used for bone defect and soft tissue augmentation. We experienced 31-year-old male patient who injured open depressed fracture of right temporal bone. He was operated with autogenous bone graft for bone defect area and silicone implants for soft tissue augmentation. After about 6 years later, mass palpated in right temporal area. There was no inflammatory sign in physical examination and CT finding. So we removed hyperfibrotic tissue totally with previous inserted silicone implants and augmented soft tissue with pored Medpor(R) block. In light microscopic findings, only tissue hyperfibrosis were proved without inflammatory cell, such as giant cell or ephithelioid cell.
Adult
;
Cartilage
;
Depression
;
Giant Cells
;
Humans
;
Male
;
Physical Examination
;
Silicone Elastomers
;
Temporal Bone
;
Transplants
3.Intracoronary Ultrasound in Patients with Coronary Vasospasm or Vasoconstriction.
Hyeon Cheol GWON ; Jae Choon RYU ; Byung Ryul JO ; Myeong Gon KIM ; Seung Woo PARK ; Joon Soo KIM ; Duk Kyung KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jung Euy PARK ; Won Ro LEE
Korean Circulation Journal 1997;27(3):296-302
BACKGROUND: It has been hypothesized that early atherosclerosis may be related to the pathogenesis of coronary vasospasm. This study was designed to investigate the relationship between early atherosclersosis and coronary vasospasm or vasoconstriction in response to axetylcholine utilizing intravascular ultrasonography. METHOD: Total 43 segments were analyzed from subjects who were composed of 10 patients with and 7 patients without coronary vasospasm in response to intra coronary acetylcholine infusion. Spasm segment(Sp) was defined as total or subtotal occlusion, constriction segment(C) as diameter decrease>/=10%, and normal segment(N) as diameter decrease<10% compared to baseline coronary angiogram. Atherosclerotic plaque thickness was defined as the sum of thickness of intimal leading edge and sonolucent zone. Atherosclerosis was defined as atherosclerotic plaque thickness > 0.5mm. RESULTS: The atherosclerotic plaques of spasm segments were significantly thicker than those of normal and constriction segments(spasm segments : 1.19+/-0.21mm, constrict segments : 0.58+/-0.11mm, normal segment : 0.37+/-0.11, p<0.05). Atherosclerosis was present in 90% of spasm segments. Among normal of constriction segments, atherosclerotic plaque thickness of patients with vasospasm was thicker than that of patients without vasospasm, although it was statistically insignificant(patients with vasospasm : 0.65+/-0.51mm, patients without vasospasm 0.36+/-0.39mm, p=0.07). Frequency of atherosclerosis in normal or constriction segments was significantly higher in patients with vasospasm than patients without vasospasm(patients with vasospasm 47%, patients without vasospasm : 11%, p<0.05). CONCLUSION: Atherosclerosis is present at segments of vasospasm in response to intracoronary acetylcholine. Even among normal or constriction segments, the artherosclerotic plaque thickness of patients with vasospasm was thicker than that of patients without vasospasm which may indicates that coronary vasospasm is a diffuse early atherosclerotic disease.
Acetylcholine
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Atherosclerosis
;
Constriction
;
Coronary Vasospasm*
;
Humans
;
Plaque, Atherosclerotic
;
Spasm
;
Ultrasonography*
;
Ultrasonography, Interventional
;
Vasoconstriction*
4.O-glucogenistein inhibits eosinophil recruitment and nasal allergic symptoms in a murine model of nasal allergy.
Hong Ryul JIN ; Bora SOHN ; Yuan Xi ZHE ; Young soo KIM ; Sang Hun JUNG ; Seung Ho LEE ; Jae Chun RYU ; Mi Kyeong KIM
Journal of Asthma, Allergy and Clinical Immunology 2003;23(3):467-473
BACKGROUND: Infiltration of eosinophils in the nasal mucosa is a consistent feature of nasal allergic inflammation. Various cytokines, especially interleukin-5(IL-5), were identified to play important roles in the infiltration and activation of eosinophils in nasal mucosa. Our previous study found that among 4 kinds of sophoricosides extracted from Sophora japonica, named sophi, orobol, genistin, and genistein, 3 compounds except genistein known as protein tyrosine kinase(PTK) inhibitor had anti-inflammatory and anti-IL-5 effects, and sophi was the most potent. OBJECTIVE: The goal of this study was to investigate the antagonism of sophi on the nasal eosinophilia in ovalbumin(OA)-sensitized murine nasal allergy model. METHODS: Male BALB/c mice sensitized intraperitoneally and then topically with OA were treated with sophi(10 or 30mg/kg) or anti-mouse IL-5 monoclonal antibody(anti-IL-5 mAb, 1mg/Kg) intravenously 1 hour before challenge. The effect of sophi on the infiltration of eosinophils into the nasal mucosa, peripheral blood eosinophilia, nasal symptom, and OA-specific IgE antibody production were evaluated. Results: Administration of sophi(10, 30mg/kg) significantly inhibited the nasal eosinophil infiltration and nasal symptom compared to that of anti-IL-5 mAb. But eosinophil count inthe peripheral blood and the titer of OA-specific IgE were not affected by sophi. CONCLUSION: Sophi inhibited not only the tissue eosinophilia but also the acute nasal allergic symptom. These findings suggest that sophi has anti-eosinophilic cytokine activity and also plays blockade of early allergic reaction. Taken together, sophi may be a candidate for new anti-allergic medicine.
Animals
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Antibody Formation
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Cytokines
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Eosinophilia
;
Eosinophils*
;
Genistein
;
Humans
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Hypersensitivity*
;
Immunoglobulin E
;
Inflammation
;
Interleukin-5
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Male
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Mice
;
Nasal Mucosa
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Sophora
;
Tyrosine
5.Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells.
Esder LEE ; Jun Mo YU ; Min Kyung LEE ; Gyeong Ryul RYU ; Seung Hyun KO ; Yu Bae AHN ; Sung Dae MOON ; Ki Ho SONG
Korean Diabetes Journal 2009;33(6):475-484
BACKGROUND: Despite a recent breakthough in human islet transplantation for treating type 1 diabetes mellitus, the limited availability of donor pancreases remains a major obstacle. Endocrine cells within the gut epithelium (enteroendocrine cells) and pancreatic beta cells share similar pathways of differentiation during embryonic development. In particular, K-cells that secrete glucose-dependent insulinotropic polypeptide (GIP) have been shown to express many of the key proteins found in beta cells. Therefore, we hypothesize that K-cells can be transdifferentiated into beta cells because both cells have remarkable similarities in their embryonic development and cellular phenotypes. METHODS: K-cells were purified from heterogeneous STC-1 cells originating from an endocrine tumor of a mouse intestine. In addition, a K-cell subclone expressing stable Nkx6.1, called "Kn4-cells," was successfully obtained. In vitro differentiation of K-cells or Kn4-cells into beta cells was completed after exendin-4 treatment and serum deprivation. The expressions of insulin mRNA and protein were examined by RT-PCR and immunocytochemistry. The interacellular insulin content was also measured. RESULTS: K-cells were found to express glucokinase and GIP as assessed by RT-PCR and Western blot analysis. RT-PCR showed that K-cells also expressed Pdx-1, NeuroD1/Beta2, and MafA, but not Nkx6.1. After exendin-4 treatment and serum deprivation, insulin mRNA and insulin or C-peptide were clearly detected in Kn4-cells. The intracellular insulin content was also increased significantly in these cells. CONCLUSION: K-cells are an attractive potential source of insulin-producing cells for treatment of type 1 diabetes mellitus. However, more experiments are necessary to optimize a strategy for converting K-cells into beta cells.
Animals
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Blotting, Western
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C-Peptide
;
Diabetes Mellitus, Type 1
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Embryonic Development
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Endocrine Cells
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Enteroendocrine Cells
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Epithelium
;
Female
;
Glucokinase
;
Humans
;
Immunohistochemistry
;
Insulin
;
Insulin-Secreting Cells
;
Intestines
;
Islets of Langerhans Transplantation
;
Mice
;
Pancreas
;
Peptides
;
Phenotype
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Pregnancy
;
Proteins
;
RNA, Messenger
;
Tissue Donors
;
Venoms
6.Distal Radioulnar Joint Injuries Associated with Intra-articular Fracture of Distal Radius.
Woo Sik KIM ; Yong Sang KIM ; Whan Yong CHUNG ; Woo Suk LEE ; Taek Soo JEON ; Seung Ryul RYU
Journal of the Korean Fracture Society 2006;19(2):221-227
PURPOSE: To evaluate the significance of distal radioulnar joint injury which may affect the postoperative radiologic and clinical results of AO classification, type C distal radius fractures. MATERIALS AND METHODS: From October 2000 to October 2005, 58 patients of AO classification, type C distal radius fracture, who had been treated with operative methods were studied. They are thirty-six men and twenty-two women. The average follow up period was 14 months. The patients were divided into five groups. In the first group (13 cases), there was no distal radioulnar joint injuries. In the second group (20 cases), there were ulnar styloid fractures. In the third group (11 cases), there were separation of distal radioulnar joint. In the fourth group (9 cases), there were ulnar styloid fractures with separation of distal radioulnar joint. In the fifth group (5 cases), there were displacement of ulna in sagittal plane. We measured the radial length, radial inclination and volar tilt in plain radiograph in each group and analyzed the results through Scheck's methods. To analyzed the clinical results, we used the Demerit Point System by Sarmiento. RESULTS: There was no significant differences in radiologic and clinical results among the five groups. CONCLUSION: According to compairing the radiologic results of each group which was suspicious of distal radioulnar joint injuries, in the intraarticular comminuted fractures of distal radius, the distal radioulnar joint injuries did not affect the results of treatment when anatomical reduction of distal radius was achieved.
Classification
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Female
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Follow-Up Studies
;
Fractures, Comminuted
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Humans
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Intra-Articular Fractures*
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Joints*
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Male
;
Radius Fractures
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Radius*
;
Ulna
7.The Clinicopathologic Significance of a p63 Expression in Invasive Breast Cancer.
Sung Ryul LEE ; Jae Seung CHO ; Kwang Dae HONG ; Woo Sang RYU ; Jea Bok LEE ; Gil Soo SON ; Jung Won BAE ; Ae Ree KIM ; Bum Hwan KOO
Journal of the Korean Surgical Society 2006;71(4):243-249
PURPOSE: p63 is a recently described as p53 homologue. Despite their structural homologies, they have different activities. p63 is a specific myoepithelial cell marker in normal breast tissue and it is expressed in a minority of breast cancers. The aim of this study was to evaluate the prognostic significance of the p63 expression in breast cancer. METHODS: The expression of p63 in breast cancer was determined by performing immunohistochemistry on 350 patients who underwent mastectomy at the Department of Surgery at Korea University Medical Center between January 1992 and September 2004. A retrospective analysis was conducted using the medical records. A tissue microarray was constructed, and immunohistochemical analysis for p63 was performed according to the usual methods. RESULTS: Among 350 patients, 40 (11.4%) showed a p63 expression. There was a significant correlation between p63 and the histologic grade. There were significant correlations of p63 with p53 and HER2/neu, respectively. In the basal type of breast cancer, the p63 expression was significantly higher than in the luminal type of breast cancer. The 5 year disease free survival rates were 69% in the patients with a p63 expression and 76% in the patients without a p63 expression, but there was no statistical difference. CONCLUSION: The present results indicate that a p63 expression is associated with a high grade tumor, a p53 expression and a HER2/neu expression in breast cancer, which are the known poor prognostic factors of breast cancer. Immunohistochemical subtyping shows that the p63 expression is a useful predictor for the basal type of breast cancer. In addition, this study suggests that the p63 expression in the basal type of breast cancer is associated with a poor prognosis.
Academic Medical Centers
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Breast Neoplasms*
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Breast*
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Disease-Free Survival
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Humans
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Immunohistochemistry
;
Korea
;
Mastectomy
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Medical Records
;
Phenobarbital
;
Prognosis
;
Retrospective Studies
8.Gastrointestinal Stromal Tumor (GIST) of the Stomach: Clinicopathologic Analysis and Outcome.
Je Seock RYU ; Sung Ryul LEE ; Sae Byeol CHOI ; Sung Soo PARK ; Ju Han LEE ; Seung Joo KIM ; Chong Suk KIM ; Yang Seok CHAE ; Young Jae MOK
Journal of the Korean Gastric Cancer Association 2005;5(1):40-46
PURPOSE: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. GISTs are positive for the expression of c-Kit protein at immunohistochemistry, and their clinical presentations vary. This retrospective study was performed to evaluate the clincopathologic characteristics of GISTs and to define the prognostic factors. MATERIALS AND METHODS: 40 patients who underwent a complete resection of a GIST during the period 1996~2003 at the Department of Surgery, Korea University College of Medicine, were studied. We divided them into low- and high-risk groups by using tumor size and mitotic count: 23 cases were low risk, and 17 were high risk. Clinicopathologic features, immunohistochemical findings, and prognoses were compared between the low- and the high-risk groups. RESULTS: The mean age of the 40 patients was 61.3+/-11.1 years, and the male-to-female ratio was 1:1.1. There was no significant difference in age and sex between the groups. A comparative analysis revealed tumor size, mitotic count, clinical symptoms, preoperative pathologic diagnosis, ulceration, and necrosis to be variables that had statistically significant differences between the high- and the low-risk groups. In the univariate analysis, tumor size, mitotic count, ulceration, necrosis, and abnormal endoscopic ultrasound findings were associated with disease-free survival, but in the multivariate analysis, mitotic activity was the only independent factor associated with disease-free survival. 8 patients had recurrences during the follow-up period, and four of them were treated with STI-571 (imatinib mesylate, Gleevec(R)). The treated patients have survived until now; however, two of non-treated patients died from disease progression. CONCLUSION: Based on this study, tumor size, ulceration, and necrosis are significant factors affecting survival, and mitotic activity may be a useful prognostic marker. STI-571 may be used in an adjuvant setting because the drug has shown anticancer activity in patients with recurrence or metastasis.
Diagnosis
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Disease Progression
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Disease-Free Survival
;
Follow-Up Studies
;
Gastrointestinal Stromal Tumors*
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Gastrointestinal Tract
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Humans
;
Immunohistochemistry
;
Korea
;
Mesylates
;
Multivariate Analysis
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Necrosis
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Neoplasm Metastasis
;
Prognosis
;
Proto-Oncogene Proteins c-kit
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Recurrence
;
Retrospective Studies
;
Stomach*
;
Ulcer
;
Ultrasonography
;
Imatinib Mesylate
9.Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate.
Gyeong Ryul RYU ; Jun Mo YOO ; Esder LEE ; Seung Hyun KO ; Yu Bae AHN ; Ki Ho SONG
Diabetes & Metabolism Journal 2011;35(1):65-71
BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise mechanism of this adverse effect is not well understood. METHODS: INS-1 rat-derived insulin-secreting cells were exposed to 30 mM glucose and 0.25 mM palmitate for 48 hours. RESULTS: The production of reactive oxygen species increased significantly. Pancreatic and duodenal homeobox 1 (Pdx1) expression was down-regulated, as assessed by reverse transcription-polymerase chain reaction and Western blot analyses. The promoter activities of insulin and Pdx1 were also diminished. Of note, there was nucleocytoplasmic translocation of Pdx1, which was partially prevented by treatment with an antioxidant, N-acetyl-L-cysteine. CONCLUSION: Our data suggest that prolonged exposure of beta cells to elevated levels of glucose and palmitate negatively affects Pdx1 expression via oxidative stress.
Apoptosis
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Blotting, Western
;
Diabetes Mellitus, Type 2
;
Fatty Acids
;
Genes, Homeobox
;
Glucose
;
Insulin
;
Insulin-Secreting Cells
;
Oxidative Stress
;
Reactive Oxygen Species
10.Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic beta-Cell Injury.
Eun Mi LEE ; Young Eun LEE ; Esder LEE ; Gyeong Ryul RYU ; Seung Hyun KO ; Sung Dae MOON ; Ki Ho SONG ; Yu Bae AHN
Diabetes & Metabolism Journal 2011;35(5):469-479
BACKGROUND: Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic beta-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic beta-cells from high glucose-induced apoptosis. METHODS: Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations. RESULTS: CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP. CONCLUSION: Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.
Apoptosis
;
Caspase 3
;
Cell Survival
;
Diabetes Mellitus
;
Flow Cytometry
;
Glucose
;
Heme
;
Heme Oxygenase-1
;
Insulin
;
Protoporphyrins
;
Reactive Oxygen Species
;
RNA, Messenger
;
Up-Regulation