BACKGROUND: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice.METHODS: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase α (G6Pase-α), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ζ (PKCζ) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice.RESULTS: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a 40 μM concentration without a change in G6Pase-α expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 (p-IRS-1-Ser302) and decreased p-IRS-1-Tyr632 dose-dependently. Telmisartan dose-dependently increased p-PKCζ-Thr410 which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative PKCζ significantly attenuated telmisartan-induced HGP and p-IRS-1-Ser302 and -inhibited p-IRS-1-Tyr632. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased p-IRS-1-Ser302 and decreased p-IRS-1-Tyr632, which was accompanied by an increase in p-PKCζ-Thr410.CONCLUSION: These results suggest that telmisartan increases HGP by inducing p-PKCζ-Thr410 that increases p-IRS-1-Ser302 and decreases p-IRS-1-Tyr632 in a PPARγ-independent manner.
Animals ; Blotting, Western ; Diabetes Mellitus, Type 2 ; Diet, High-Fat ; Ectopic Gene Expression ; Glucose ; Glucose-6-Phosphatase ; Hep G2 Cells ; Insulin Receptor Substrate Proteins ; Insulin ; Liver ; Losartan ; Mice ; Peroxisomes ; Phosphoenolpyruvate ; Phosphorylation ; Protein Kinase C ; Protein Kinases ; Receptor, Angiotensin, Type 1 ; Receptor, Insulin ; Serine

BACKGROUND: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. METHODS: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase α (G6Pase-α), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ζ (PKCζ) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. RESULTS: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a 40 μM concentration without a change in G6Pase-α expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 (p-IRS-1-Ser302) and decreased p-IRS-1-Tyr632 dose-dependently. Telmisartan dose-dependently increased p-PKCζ-Thr410 which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative PKCζ significantly attenuated telmisartan-induced HGP and p-IRS-1-Ser302 and -inhibited p-IRS-1-Tyr632. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased p-IRS-1-Ser302 and decreased p-IRS-1-Tyr632, which was accompanied by an increase in p-PKCζ-Thr410. CONCLUSION These results suggest that telmisartan increases HGP by inducing p-PKCζ-Thr410 that increases p-IRS-1-Ser302 and decreases p-IRS-1-Tyr632 in a PPARγ-independent manner.

BACKGROUND: Intention to leave was an important managerial issue among physicians working in public health centers. This study was conducted to explore the relationship between job participations and intention to leave among physicians working in health centers. METHODS: A cross-sectional questionnaire survey was conducted to gather information about job participation, intention to leave and demographics among physicians (n=243) in public health centers in Korea. Job participation was measured by 15 items categorized 3 dimensions. Multiple regression analysis was performed to determine the effect of job participation on intent to leave among physicians working in public health center. RESULTS: Participation of medical treatment and administrative job were significantly associated with intention to leave adjusted for sex, age, income, working area, working duration, tenure, and overall job satisfaction. Therefore, physicians who actively participated in administrative job showed a lower turnover intention. Physicians who actively participated in medical treatment job had a higher quit intention. CONCLUSION: To retain qualified physicians in public health center, education should be reinforced to physician for administrative capacity building.
Capacity Building ; Demography ; Education ; Intention* ; Job Satisfaction ; Korea ; Public Health Practice ; Public Health*

We evaluated the effectiveness of Tc-99m labeled antigranulocyte antibody immunoscintigraphy in differentiating the causes of vertebral compression fracture. This study involved 16 patients with vertebral compression fracture; 8 were due to trauma or osteoporosis, 3 were due to metastasis and 5 were due to tuberculous spondylitis. We retrospectively analyzed the location and the extent of decreased tracer uptake in tomographic images of Tc-99m labeled antigranulocyte antibody immunoscintigraphy. Eight patients had a 16 vertebral compression fractures due to trauma or osteoporosis , three patients had a 3 vertebral compression fractures due to metastasis and 5 patients had a 6 vertebral compression fractures due to tuberculous spondylitis. Sixteen vertebral compression fractures by trauma or osteoporosis showed a normal tracer uptake in pedicle, laminar and spinous process, but there was noted with 6 decreased uptake, 8 absence of tracer uptake and 2 normal tracer uptake in the vertebral body. Two vertebral compression fractures by metastasis showed the absence of uptake in vertebral body, pedicle, laminar and spinous process, and one showed an absence of vertebral body and spinous process. Six vertebral compression fractures by tuberculous spondylitis showed the absence of uptake in six compression fractures, the absence of pedicle in five compression fractures. We concluded Tc-99m labeled antigranulocyte antibody immunoscintigraphy may be helpful to differentiate the causes of vertebral compression fractures.
Fractures, Compression* ; Humans ; Neoplasm Metastasis ; Osteoporosis ; Retrospective Studies ; Spondylitis

For the patients suffering from extensive deep vein thrombosis (DVT), the placement of an inferior vena cava (IVC) filter in conjunction with anticoagulant therapy has been used to prevent pulmonary embolisms. However, for the patients who anticoagulant is contraindicated or if this is complicated, the use of an IVC filter without concurrent anticoagulation may become the sole treatment for pulmonary embolisms. In this situation, the thrombi trapped in the IVC filter may cause significant clinical problems. We report here on a case of IVC filter thrombosis that was successfully treated by aspiration thrombectomy after placing another filter proximal to the previous filter.
Humans ; Pulmonary Embolism ; Thrombectomy* ; Thrombosis* ; Vena Cava Filters* ; Vena Cava, Inferior* ; Venous Thrombosis

Eighty five patients of oral cavity cancer, treated with radiation at the Department of Therapeutic Radiology, Korea Cancer Center Hospital, during the period from March 1985 to September 1990 were analyzed retrospectively. Among 85 patients, 37 patients were treated with radiation only and 48 patients were treated with radiation following surgery And 70 patients received external irradiation only by 60Co with or without electron, the others were 7 patients for external irradiation plus interstitial implantation and 8 patients for external irradiation plus oral cone electron therapy. Primary sites were mobile tongue for 40 patients, mouth floor for 17 patients, palate for 12 patients, gingiva including retromolar trigone for 10 patients, buccal mucosa for 5 patients, and lip for 1 patient. According to pathologic classification, squamous cell carcinoma was the most common (77 patients). According to AJC TNM stage, stage I + II were 28 patients and stage III+IV were 57 patients. Acturial overall survival rate at 3 years was 43.9%, 3 year survival rates were 60.9% for stage I + II, and 23.l% for stage III+IV, respectively. As a prognostic factor, primary T stage was a significant factor (p<0.01). The others, age, location, lymph node metastasis, surgery, radiation dose, and cell differentiation were not statistically significant. Among those factors, radiation plus surgery was more effective than radiation only in T3+T4 or in any N stage although it was not statistically sufficient(p<0.1). From those results, it was conclusive that definitive radiotherapy was more effective than surgery especially in the view of pertainig of anatomical integrity and function in early stage, and radiation plus surgery was considered to be better therapeutic tool in advanced stage.
Carcinoma, Squamous Cell ; Cell Differentiation ; Classification ; Gingiva ; Humans ; Korea ; Lip ; Lymph Nodes ; Mouth Floor ; Mouth Mucosa ; Mouth* ; Neoplasm Metastasis ; Palate ; Radiation Oncology ; Radiotherapy* ; Retrospective Studies ; Survival Rate ; Tongue

PURPOSE: The authors conducted a retrospective analysis of patients with the carcinoma of uterine cervix treated with curative radiation therapy to evaluated the prognostic factors that would affect the results of the therapy and to get the critical ideas in determining more aggressive treatment schedule. METHODS AND MATERIALS: From January 1987 to December 1988, Four hundreds and sixty patients with uterine cervical carcinomas treated with radiotherapy at KCCH were registered to this retrospective study. One hundred and three patients were treated with external radiation therapy alone, and 357 patients were treated with external radiation followed by low dose rate intracavitary radiation therapy. He follow-up rate was 88% and median follow-up duration was 48 months. RESULTS: The overall 5 year survival rate of the patients was 67.7%, and when classified by FIGO stages, 5 year survival rates were 81.2%, 76.3%, 73.1%, 50%, 52.3%, 11.5% for stages Ib, IIa, IIb, IIIa, IIIb, IVa respectively. Tumor size(p=0.0002), endocervical growth pattern(p=0.003), lymph node invasion(p=0.0001), mean hemoglobin level(p=0.0001), and pathologic cell type(p=0.0001) were significant prognostic factors and decrease in survival for young age patient group was marginally important(p=0.03). CONCLUSION: Significant prognostic factors I the radiation therapy of the uterine cervical carcinoma were tumor size, growth pattern of tumor, lymph node invasion, pathologic cell type, hemoglobin level of patients during treatment and lower survival rate in young age group was obvious, too. Patients with large size tumor(> or =4cm), especially combined with endocervical growth patterns or advanced stages(III or more) need more aggressive treatment to improve the outcome of treatment. And positive feature of lymph node invasion affected the result of therapy, so improvement in the diagnostic and therapeutic trial is essential.
Appointments and Schedules ; Cervix Uteri* ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Radiotherapy ; Retrospective Studies ; Survival Rate

Total of 53 patients of unresectable and recurrent rectal cancer treated with neutron beam during the period from Oct. 1987 to Apr. 1992 were analyzed. Dose fractionation for the neutron only group was 1.5 Gy per fraction, 3 fraction per week, 21 Gy/41/2 wks for 42 patients out of 53(76%). Neutron only but modified fractionation schedule (10% more or less of total dose) was applied for 9 patients, and mixed team (neutron boost) was for 4 patients. Complete tumor response was obtained in 40 patients(76% response rate). Local control rate was 28 out of 53(53%). Statistically significant better prognostic factors for local control were age below 49 years old (15/22, 68%) than above 50 years old (13/31, 42%), male (20/32, 63%) than female(8/21, 38%), tumor size less than 5 cm and non-metastatic(16/24, 67%) than size more than 5 cm or metastatic(12/29, 4l%). Major complication had developed in 7 patients (13%). Two year overall survival rate by Kaplan-Meier method was 30%, but it was rised to, 47% when the tumor was less than 5cm non-metastatic.
Appointments and Schedules ; Dose Fractionation ; Humans ; Male ; Middle Aged ; Neutrons* ; Rectal Neoplasms* ; Survival Rate

The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular localization. Analysis of western blots showed that there were no differences in the hippocampal and cortical RAGE levels in 10-month-old adult 3xTg-AD mice, but significant increases in RAGE expression were found in the 22- to 24-month-old aged 3xTg-AD mice compared with those of age-matched controls. RAGE-positive immunoreactivity was observed primarily in neurons of aged 3xTg-AD mice with very little labeling in non-neuronal cells, with the notable exception of RAGE presence in astrocytes in the hippocampal area CA1. In addition, RAGE signals were co-localized with the intracellular amyloid precursor protein (APP)/amyloid beta (Abeta) but not with the extracellular APP/Abeta. In aged 3xTg-AD mice, expression of human tau was observed in the hippocampal area CA1 and co-localized with RAGE signals. The increased presence of RAGE in the 3xTg-AD animal model showing critical aspects of AD neuropathology indicates that RAGE may contribute to cellular dysfunction in the AD brain.
Advanced Glycosylation End Product-Specific Receptor ; Alzheimer Disease/genetics/*metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Astrocytes/*metabolism ; CA1 Region, Hippocampal/growth & development/metabolism/pathology ; Humans ; Mice ; Mice, Transgenic ; Neurons/*metabolism ; Receptors, Immunologic/genetics/*metabolism ; tau Proteins/genetics/metabolism

PURPOSE: Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. MATERIALS AND METHODS: Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. RESULTS: In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. CONCLUSIONS: We suggested that TLE1 expression is a good prognostic indicator in GCs.
Carcinogenesis ; Chungcheongnam-do ; Classification ; Co-Repressor Proteins ; Gastric Mucosa ; Humans ; Joints ; Kaplan-Meier Estimate ; Male ; Stomach Neoplasms* ; Survival Rate ; Tissue Array Analysis