Apoptosis has ernerged as a key mechanism for regulating the number of leukocytes at sites of inflammation. Besides withdrawal of inflammatory stimuli, apoptosis of human monocytes can be directly triggered through two cell surface molecules, Fas and the IL-4 receptor. In contrast to Fas-mediated death which utilizes reactive oxygen intermediates (ROI) as instruments of death, IL-4-induced apoptosis of monocytes was neither blocked by antioxidants, nor accompanied by elevation of cellular ROI. Moreover, PMA which upregulates protein kinase C (PKC) inhibited IL-4-, but not Fas-mediated death. These data define a ROl-dependent, PKC-resistant Fas pathway, and a ROl-independent, PKC-susceptible IL-4 pathway of apoptosis. Monocyte apoptosis triggered by depletion of inflammatory mediators resembles the IL-4 pathway. Within the context of an inflammatory site, monocyte accumulation and depletion may be susceptible to manipulation through these pathways.
Antioxidants ; Apoptosis ; Humans* ; Inflammation ; Interleukin-4* ; Leukocytes ; Monocytes* ; Oxygen ; Protein Kinase C ; Receptors, Interleukin-4

OBJECTIVES: To determine the relationship between exercise and the incidence of type 2 diabetes in an impaired fasting glucose group. METHODS: This prospective cohort study was conducted in 19,440 men and 4,297 women, aged 30-69 years, with impaired fasting glucose at baseline who had undergone biennial medical evaluation through the National Health Insurance Corporation from 2000 to 2004. Impaired fasting glucose was defined as fasting glucose of 100 to 125 mg/dl and the subjects were divided into 3 groups depending on weekly exercise frequency. Multivariate logistic regression analysis was used to evaluate the association between the baseline exercise status and incidence of type 2 diabetes. RESULTS: During the 4-year follow-up, a total of 3,239 men and 283 women developed type 2 diabetes, a cumulative incidence of 16.6% for men, and 6.5% for women. Also, 1,688 men (21.2%) and 127 women (15.2%) developed type 2 diabetes in the obese group. The adjusted relative risk (RR) of developing type 2 diabetes in non-exercising men was significantly higher than exercising men regularly (RR= 1.375, 95% CI=1.236-1.529)(p<0.0001), and the RR for non-exercising women was higher than exercising women regularly (RR=1.124, 95% CI=0.711-1.778). The RR for non-exercise men/women in the obese group was 1.571 (95% CI=1.351-1.827)(p<0.0001)/1.869(95% CI=0.846-4.130). CONCLSIONS: Regular exercise is effective in preventing type 2 diabetes in people with impaired fasting glucose, and particularly in obese people. People with risk factors for diabetes should participate in a regular exercise program.
Adult ; Aged ; *Blood Glucose ; Diabetes Mellitus, Type 2/*epidemiology/prevention & control ; *Exercise ; Female ; Glucose Tolerance Test ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Sex Factors

BACKGROUND/AIMS: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. METHODS: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. RESULTS: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. CONCLUSIONS: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.
Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Apoptosis/drug effects ; Autophagy/drug effects ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Survival/*drug effects ; Deoxycytidine/analogs & derivatives/pharmacology ; Drug Resistance, Neoplasm/*drug effects ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Microtubule-Associated Proteins/metabolism ; Pancreatic Neoplasms/*drug therapy ; Quercetin/pharmacology

When cells are first exposed to low levels of oxidative stress, they develop a resistance to a subsequent challenge of the same stress, even at higher levels. Although some protein(s) induced by oxidative stress likely mediated this adaptive response, the nature of these proteins is unknown. In this study, the total proteins extracted from human U937 leukemia cells exposed to 50 mM H2O2 for 24 h to induce an optimal protective response were analyzed by two-dimensional polyacrylamide gel electrophoresis. H2O2 treatment induced elevation of level of 34 protein spots. An analysis of these spots by a matrix associated laser desorption/ionization time-of-flight mass spectrometry identified 28 of the H2O2-induced proteins. These include proteins involved in energy metabolism, translation and RNA processing, chaperoning or mediating protein folding, cellular signaling, and redox regulation, as well as a mitochondrial channel component, and an actin-bundling protein. Therefore, it appears that the cellular adaptation to oxidative stress is a complex process, and is accompanied by a modulation of diverse cellular functions.
Adaptation, Physiological/drug effects/*physiology ; Cells, Cultured ; Human ; Hydrogen Peroxide/*pharmacology ; Proteins/drug effects/*metabolism ; Proteomics/*methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; U937 Cells

Undifferentiated sarcoma is one of the rare primary malignant tumor of the liver typically occur ring in later childhood. It has also been referred to embryonal sarcoma or malignant mesenchymoma. In Korea, three child and two adult cases have been reported to date in liter ature. We experienced a case of undifferentiated sarcoma in a 65- year- old female who presented with abdominal pain and right upper quadrant mass . Contrast-enhanced abdominal CT scan revealed a well demarcated mass with low at tenuation and sept ation at left lobe of the liver and the mass showed hypovas cular pattern on hepatic angiography. On cross section, the tumor was well demarcated from the adjacent liver by afibr ouspseudocapsule and showed cystic degener ation. Pathologically, the tumor was consistent with an undifferentiated sarcoma of the liver.
Abdominal Pain ; Adult* ; Angiography ; Child ; Female ; Humans ; Korea ; Liver* ; Mesenchymoma ; Sarcoma* ; Tomography, X-Ray Computed

During radiotherapy of cancer, neighboring normal cells may receive sub-lethal doses of radiation. To investigate whether such low levels of radiation modulate normal cell responses to death stimuli, primary cultured human fibroblasts were exposed to various doses of gamma-rays. Analysis of cell viability using an exclusion dye propidium iodide revealed that the irradiation up to 10 Gy killed the fibroblasts only to a minimal extent. In contrast, the cells efficiently lost their viability when exposed to 0.5-0.65 mM H2O2. This type of cell death was accompanied by JNK activation, and was reversed by the use of a JNK-specific inhibitor SP600125. Interestingly, H2O2 failed to kill the fibroblasts when these cells were pre-irradiated, 24 h before H2O2 treatment, with 0.25-0.5 Gy of gamma-rays. These cytoprotective doses of gamma-rays did not enhance cellular capacity to degrade H2O2, but elevated cellular levels of p21Cip/WAF1, a p53 target that can suppress H2O2-induced cell death by blocking JNK activation. Consistently, H2O2-induced JNK activation was dramatically suppressed in the pre-irradiated cells. The overall data suggests that ionizing radiation can impart normal fibroblasts with a survival advantage against oxidative stress by blocking the process leading to JNK activation.
Antioxidants/pharmacology ; Cell Death ; Cells, Cultured ; Enzyme Activation/radiation effects ; Fibroblasts/enzymology/radiation effects ; *Gamma Rays ; Heat-Shock Proteins/metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors ; Oxidative Stress/*radiation effects ; Research Support, Non-U.S. Gov't ; Water/pharmacology

Primary adenosquamous carcinoma of the liver is a very rare type of cholangiocarcinoma and is defined as a cancer containing both squamous and adenomatous components in the same lesion. Recently, we experienced a primary adenosquamous carcinoma of the liver presented as liver abscess. A 63-year-old man was presented with a 4-day history of fever and chill. The radiologic study showed a 4 cm-sized, central hypoattenuated mass with peripheral rim enhancement in the left lobe of the liver. Ultrasonography-guided aspiration and biopsy suggested an adenocarcinoma with abscess in the liver. At laparotomy, the tumor occupied the left lobe of the liver and invaded the right diaphragm. An extended left lobectomy and a partial excision of the involved diaphragm were done. Grossly, the tumor was 6x5x5 cm in size and had an eccentric necrosis. Microscopically, the tumor was composed of adenocarcinoma and squamous cell carcinoma with a transitional area.
Carcinoma, Adenosquamous/*complications/pathology/surgery ; Case Report ; Human ; Liver Abscess/*etiology ; Liver Neoplasms/*complications/pathology/surgery ; Male ; Middle Age

BACKGROUND/AIMS: Pulmonary tuberculosis may coexist with intestinal tuberculosis even in the absence of gastrointestinal symptoms. The aim of this prospective study was to define the colonoscopic findings of early lesions of intestinal tuberculosis, incidence of asymptomatic intestinal tuberculosis in patients with active pulmonary tuberculosis and to evaluate the clinical response after standard anti- tuberculosis chemotherapy. METHODS: We examined 59 Korean patients with active pulmonary tuberculosis, who had no gastrointestinal symptoms. Patients underwent diagnostic total colonoscopy up to terminal ileum for evaluation of intestinal tuberculosis. Follow-up total colonoscopy was also done in 1~3 months after start of treatment. RESULTS: Intestinal tuberculous lesions were found in 54% of patients. The common locations of lesion were terminal ileum (84%) and cecum (69%). The combination of circumferential ulceration, hyperemic mucosa and erosions of the colon was the most common finding (37.5%), the combination of hyperemia and ulceration occurred in 34.4% of patients and hyperemia with/without erosion in 12.5%. The direction of ulceration was transevere in relation to long axis of the colon but occasionally longitudinal. Although most ulcers were multiple in number and various in size but some paitents had isolated single ulcer with erosion. All of the lesions regressed within 1~3 months of treatment. CONCLUSIONS: During screening total colonoscopy, if there are nonspecific hyperemia, erosion or shallow ulcer on colon or terminal ileum, it is necessary to check up chest X-ray for rule out tuberculous lesion, especially in countries with a high prevalence of tuberculosis.
Axis, Cervical Vertebra ; Cecum ; Colon ; Colonoscopy* ; Drug Therapy ; Follow-Up Studies ; Humans ; Hyperemia ; Ileum ; Incidence ; Mass Screening ; Mucous Membrane ; Prevalence ; Prospective Studies ; Thorax ; Tuberculosis ; Tuberculosis, Pulmonary* ; Ulcer

BACKGROUND: The purpose of this study was to investigate the ultrastructural relation of H. pylori and gastric epithelial cells in their adhesion. METHODS: Endoscopic biopsy of gastric antrum and body was performed from 15 patients (9 men, 6 women) with chronic gastritis. These specimens were processed and observed by transmission electron microscope (Hitachi H-600). RESULTS: On the basis of morphological appearances, the different types of adhesion of the organism with the epithelial cells were categorized as filamentous connection, adhesion pedestals, membrane fusion. Coccoid and intermediate forms were associated with filamentous connection whereas bacillary forms were associated with adhesion pedestals and membrane fusion. CONCLUSION: Various types of adhesion were associated with H. pylori and gastric epithelium. Further studies are needed to investigate biophysiologic influence to epithelial cells by ultrastructural relationship.(Korean J Med 60:16-21, 2001)
Biopsy ; Epithelial Cells* ; Epithelium ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Humans ; Male ; Membrane Fusion ; Microscopy, Electron ; Pyloric Antrum

BACKGROUND: Gastrointestinal stromal tumors (GISTs) have the subject of debate and controversy regarding their histogenesis, criteria on malignancy, prognostic features, site-specificity and their nomenclature. These tumors have various phenotypical features and are generally divided into (1) tumors showing differentiation toward smooth muscle cells (2) tumors showing apparent differentiation toward neural elements (3) tumors showing dual differentiation toward smooth muscle and neural elements (4) tumors lacking differentiation toward either cell type (uncommitted type). This study was performed to identify the possible origin and differentiation of gastric stromal tumor. METHODS: This study was performed on 38 patients who had gastric stromal tumors on endoscopy or endoscopic ultrasonography and confirmed by endoscopic or surgical resection between January 1994 and June 1999 at Department of Internal Medicine, Korea University College of Medicine. Formalin-fixed, paraffin-embedded tissues were studied by immunohistochemical method for detecting the presence of CD 34, CD 117, Vimentin, SMA, Desmin, S-100, PGP 9.5 and NSE. RESULTS: The patients' age ranged from 26 to 81 years old, with an average age of 53.8 years. The male to female ratio was 1:1.2. Endoscopic resections were performed on 22 patients and surgical operations on 16 patients. The average tumor size was 25.3 mm in diameter. On immunohistochemical staining method, the uncommitted type was found in 18 patients (47.4%), of which 17 patients (94.4%) were CD117 (+), CD34 (+), Vimentin (+), 12 patients (31.6%) had muscular differentiation, 7 patients (18.4%) showed neural differentiation and 1 patient (2.6%) showed differentiation toward both neural and muscular immunohistochemical pattern. CONCLUSION : Gastric stromal tumors showed phenotypical diversity in immunohistochemical staining suggesting different histogenesis. Most uncommitted type had a phenotype of intersititial cells of Cajal (ICC) and this evidence supports the hypothesis that uncommitted type has the origin of ICC.
Aged, 80 and over ; Desmin ; Endoscopy ; Endosonography ; Female ; Gastrointestinal Stromal Tumors ; Humans ; Immunohistochemistry ; Internal Medicine ; Korea ; Male ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Phenotype ; Stomach ; Vimentin