• Clinical and Experimental Pediatrics
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• v.52 no.8
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• pp.944-952
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• 2009

Purpose : To investigate the effects of angiotensin II inhibition on the epithelial to mesenchymal transition (EMT) in the developing kidney, we tested the expression of EMT markers and nestin in angiotensin converting enzyme (ACE) inhibitor-treated kidneys. Methods : Newborn rat pups were treated with enalapril (30 mg/kg/d) or a vehicle for 7 days. Immunohistochemistry for the expression of ${\alpha}$-smooth muscle actin (SMA), E-cadherin, vimentin, and nestin were performed. The number of positively-stained cells was determined under 100 magnification in 10 random fields. Results : In the enalapril-treated group, ${\alpha}SMA-positive$ cells were strongly expressed in the dilated tubular epithelial cells. The number of ${\alpha}SMA-positive$ cells in the enalapril-treated group increased in both the renal cortex and medulla, compared to the control group (P<0.05). The expression of E-cadherin-positive cells was dramatically reduced in the cortical and medullary tubular epithelial cells in the enalapril-treated group (P<0.05). The number of vimentin- and nestin-positive cells in the cortex was not different in comparisons between the two groups; however, their expression increased in the medullary tubulointerstitial cells in the enalapril-treated group (P<0.05). Conclusion : Our results show that ACE inhibition in the developing kidney increases the renal EMT by up-regulating ${\alpha}SMA$ and down-regulating E-cadherin. Enalapril treatment was associated with increased expression of vimentin and nestin in the renal medulla, suggesting that renal medullary changes during the EMT might be more prominent, and ACE inhibition might differentially modulate the expression of EMT markers in the developing rat kidney.

• Development and Reproduction
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• v.15 no.4
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• pp.349-357
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• 2011

Since nesfatin-1/NUCB2 involved in the control of appetite and energy metabolism was discovered for the first time in hypothalamus, many reports have shown its expression in various tissues. We also recently demonstrated that nesfatin-1/NUCB2 was expressed in the reproductive organs of mouse. However, no data exist on nesfatin-1/NUCB2 expression, regulation, and secretion in the uterus. Therefore, we examined the expression of nesfatin-1/NUCB2 in mouse uterus and the effects of PMSG and estrogen on its expression. NUCB2 mRNA expression in the uterus was determined by conventional and real-time PCR and nesfatin-1 protein expression was detected by western blotting. In immunohistochemistry staining, nesfatin-1 protein was localized at the epithelial cells of the uterine glands and endometrium. Nesfatin-1 protein binding sites were displayed at the epithelial cells of uterine glands and specific granulocytes including neutrophils. Additionally, to examine if the nesfatin-1/NUCB2 expression in the uterus is regulated by gonadotropin or estrogen, ovariectomized mice were treated with PMSG or $17{\beta}$-estradiol. The expression levels of NUCB2 mRNA in the uterus was significantly increased in the control mice after PMSG treatment, but not in the ovariectomized mice. In contrast, NUCB2 mRNA expression was dramatically increased in the ovariectomized mice after treatment with $17{\beta}$-estradiol. We report here for the first time that nesfatin-1/NUCB2 mRNA and protein express in the mouse uterus and its expression is regulated by estrogen secreted from the ovary, but not gonadotropin from the pituitary.

• Applied Biological Chemistry
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• v.47 no.3
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• pp.315-320
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• 2004

The aim of this study was to develop an activator, 3-10 kDa fraction from radish water extracts, that will improve the intestinal function and bowel movement in the colons. Radish water extracts were investigated for their intestinal function effects according to the charcoal meal transit method, employing Balb/c mice: also, their anti-constipation activities were compared utilizing the loperamide-induced constipation method, employing SD rats. The result suggested that the effects of the charcoal meal transit increased remarkably in radish water extract administrated rats in comparison to loperamide administrated rats. Futhermore, the effects of various solvent extracts of radish on charcoal meal transit in Balb/c mice increased remarkably in radish water fraction administrated rats than in different solvent fraction administrated rats. Radish extraction was tested and isolated into 4 groups: below 3 kDa, 3-10 kDa, 10-300 kDa, and over 300 kDa. 3-10 kDa was the most effective on the intestinal function and bowel movement in the colons; also, 3-10 kDa fraction of radish water extraction was found to be the most effective charcoal meal transit. The dry weight and moisture content of feces remarkedly increased in the 3-10 kDa administrated rats group than in the loperamide only group. Experimental results revealed that 3-10 kDa fraction of radish water extract was the most effective on the intestinal function and bowel movement was the crypt epithelial cells that contained more MUC2 in the 3-10 kDa administrated group than the loperamide only group: in addition, the thickness of mucus layer stained with alcian blue was significantly thicker in 3-10 kDa administrated rats than in loperamide administrated rats. Crypt epithelial cells secreted more MUC2 in the 3-10 kDa administrated group than the loperamide only group and the stained cells clearly showed the MUC2 with antibody Biogenex AM358.

• Journal of Gastric Cancer
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• v.6 no.3
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• pp.146-153
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• 2006

Purpose: Gastrointestinal stromal tumorsm (GISTs) are the most common mesenchymal tumors that arise anywhere in the tubular GI tract. The prognosis for GSTIs is important because f GISTs may metastasiwx in the liver or the abdominal cavity in an early stage. For the reason we examined the tumor size, the mitotic number, ki 67, p53, and c-kit mutation as independent prognostic factor for GISTs. Materials and Methods: A retrospective study was conducted in 76 patients who had been re-evaluated for confirmation of diagnosis between Jan 1998 and Dec. 2001. at Catholic University of medicine. Results: There were significant difference between the turner size, mitotic indices, ki 67, c-kit mutations and the 5-years survival rates. Tumor size (${\geq}5\;cm$) and mitotic index (${\geq}5/50\;HPF$) were statistically related to a significantly poor prognosis (P=0.017 and P=0.042, respectively). c-kit mutations in exon 11 were found in 7 cases c-kit mutation was observed more frequently in high risk patients, and there was a significant difference between c-kit mutation and survival (P=0.037). Elevated ki 67 was noted in 34 out of the 76 cases. High risk patients showed elevated ki67 index more frequently and there was significant relation with the survival rate (P=0.0417). Conclusion: We think that tumor size, mitotic index, Ki 67 and c-kit mutation are as independent prognostic factors for GISTs, but more research is needed.

• Journal of Chest Surgery
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• v.36 no.6
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• pp.397-403
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• 2003

Background: The research sought to identify the clinical features of pleomorphic carcinoma of the lung generally known as a rare subtype in accordance with the lung cancer classification done in 1999 by WHO. Material and Method: 250 cases of surgically resected lung cancers were collected in this hospital from January 1992 to December 2001. This study included 42 cases of pleomorphic carcinoma diagnosed through light microscope and immunohistochemistry. Result: Out of 42 cases, males represented 31, and females 11, the age ranged from 26 to 77. Main clinical symptoms included coughing, hemoptysis, sputum. Diagnoses disclosed the stage as stage la in 3 cases (7%), Ib in 16 (38%), IIa in 1 (2%), IIb in 8 (19%), IIIa in 15 (35%), and IIIb in 1 (2%). Out of these, no lymph node metastasis was represented in 23 cases (54%), while N1 and N2 involving lymph node metastasis was shown 19 cases (46%). A total of 19 patients developed metastasis, comprising the brain in 5 cases (26%), bone in 4 (21%), muscle in 4 (21%), Lymph node in 2 (10%), and 1 liver, ovary, contralateral lung, and adrenal gland, respectively. The size of the tumor ranged from 1 cm to 11 cm, averaging 5.85 cm. Out of the 42 patients, the total two-year and five-year survival rates in accordance with the Kaplan-Meier method represented 26% and 13%, respectively, These figures compared to the corresponding 44% and 34% in cases other than pleomorphic carcinoma from the survey target of 256 cases, proved to be significantly low (p<0.002). No significant difference was found in the survival rates compared between age and tumor size, between stage I and above stage II, and between N0 and above N1. Patients who developed postoperative metastasis all died, and showed significantly low survival rates (p<0.002) compared to those patients without metastasis. Conclusion: With the new diagnosis method of f999 WHO's lung cancer classification applied, pleomorphic carcinoma showed a higher prevalence rate than under previous classifications, their postoperative survival rate was significantly low compared to histologic type of non small cell lung carcinomas.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.401-408
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• 2011

Type 2 diabetes mellitus (NIDDM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In order to control the type 2 diabetes mellitus, anti-hyperglycemic effect of Triticum aestivum L. water extracts (TAWE) was investigated in 7 week old male diabetic C57BL6/J-ob/ob mice. For the experiments, the diabetic animal model ob/ob mice and non-diabetic animal model lean mice were divided into 3 groups: non-treatment control group (Control), and two experimental groups orally treated with 25 or 100 mg/kg/day dose of TAWE (TAWE-25 and TAWE-100, respectively). The lean mice were used as the non-diabetic normal control. TAWE was orally administrated for 6 weeks and the diabetic clinical markers, including blood glucose level, body weight, organs weight and insulin level were determined. The oral administration of TAWE-100 in ob/ob diabetic mice significantly decreased blood glucose level (78.4%) and body weight (11.9%) compared with diabetic control group. The weights of organs, including spleen, liver, kidneys, heart and lung were not different among groups, while the treatments of TAWE-100 in ob/ob diabetic mice significantly reduced blood total cholesterol (24.35%) and triglyceride (23.97%) levels compared with the diabetic control group. The levels of serum insulin and glucose tolerance were improved after TAWE-100 treatment in ob/ob diabetic mice. Moreover, the immunohistochemical staining for insulin detection in pancreatic islet $\beta$-cells expressed high level of insulin in TAWE-100 treated ob/ob mice. From the above results, the intake of TAWE may be effective in anti-hyperglycemia by the attenuation of glucose and lipid levels. TAWE-containing diets or drugs may be beneficial for controlling diabetes mellitus type 2 in human.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.191-199
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• 2005

Background: Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy. Materials and Methods: A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of $HIF-1{\alpha}$ and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay. Results: H. pyfori-associated gastritis tissues showed significantly higher density of $CD34^+$ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of $HIF-1{\alpha}$. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis. Conclusion: The fact that PPls can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.