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.

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 ; Blotting, Western ; Diabetes Mellitus, Type 2 ; Fatty Acids ; Genes, Homeobox ; Glucose ; Insulin ; Insulin-Secreting Cells ; Oxidative Stress ; Reactive Oxygen Species

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

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4+/-8.9 yr and average disease duration was 9.6+/-6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.
Adult ; Age of Onset ; *Asian Continental Ancestry Group ; Female ; HLA-B27 Antigen/diagnostic use ; Humans ; Joints/pathology ; Male ; Severity of Illness Index ; Spondylitis, Ankylosing/diagnosis/*pathology/*physiopathology/*radiography

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 ; Blotting, Western ; C-Peptide ; Diabetes Mellitus, Type 1 ; Embryonic Development ; Endocrine Cells ; Enteroendocrine Cells ; Epithelium ; Female ; Glucokinase ; Humans ; Immunohistochemistry ; Insulin ; Insulin-Secreting Cells ; Intestines ; Islets of Langerhans Transplantation ; Mice ; Pancreas ; Peptides ; Phenotype ; Pregnancy ; Proteins ; RNA, Messenger ; Tissue Donors ; Venoms

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 ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Korea ; Mastectomy ; Medical Records ; Phenobarbital ; Prognosis ; Retrospective Studies

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 ; Female ; Follow-Up Studies ; Fractures, Comminuted ; Humans ; Intra-Articular Fractures* ; Joints* ; Male ; Radius Fractures ; Radius* ; Ulna

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 ; Disease Progression ; Disease-Free Survival ; Follow-Up Studies ; Gastrointestinal Stromal Tumors* ; Gastrointestinal Tract ; Humans ; Immunohistochemistry ; Korea ; Mesylates ; Multivariate Analysis ; Necrosis ; Neoplasm Metastasis ; Prognosis ; Proto-Oncogene Proteins c-kit ; Recurrence ; Retrospective Studies ; Stomach* ; Ulcer ; Ultrasonography ; Imatinib Mesylate

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

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 ; Antibody Formation ; Cytokines ; Eosinophilia ; Eosinophils* ; Genistein ; Humans ; Hypersensitivity* ; Immunoglobulin E ; Inflammation ; Interleukin-5 ; Male ; Mice ; Nasal Mucosa ; Sophora ; Tyrosine