• 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.

• Journal of Preventive Medicine and Public Health
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• v.39 no.3
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• pp.199-204
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• 2006

Objectives: Mercury is a hazardous organ-specific environmental contaminant. It exists in a wide variety of physical and chemical states, each of which has unique characteristics for the target organ specificity. Exposure to mercury vapor and to organic mercury compounds specifically affects the CNS, while the kidney is the target organ for inorganic Hg compounds. Methods: In this study, mercury chloride $(HgCl_2)$ was studied in a renal derived cell system, i.e., the tubular epithelial Madin-Darby canine kidney (MDCK) cell line, which has specific sensitivity to the toxic effect of mercury. MDCK cells were cultured for 6-24 hr in vitro in various concentrations (0.1-100 M) of $HgCl_2$, and the markers of apoptosis or cell death were assayed, including DNA fragmentation, caspase-3 activity andwestern blotting of cytochrome c. The influence of the metal on cell proliferation and viability were evaluated by the conventional MTT test. Results: The cell viability was decreased in a time and concentration dependent fashion: decreases were noted at 6, 12 and 24 hr after $HgCl_2$, exposure. The increases of DNA fragmentation were also observed in the concentrations from 0.1 to 10 M of $HgCl_2$ at 6 hr after exposure. However, we could not observe DNA fragmentation in the concentrations more than 25 M because the cells rapidly proceeded to necrotic cell death. The activation of caspase-3 was also observed at 6 hr exposure in the $HgCl_2$ concentrations from 0.1 to 10 M. The release of cytochrome c from the mitochondria into the cytosol, which is an initiator of the activation of the caspase cascade, was also observed in the $HgCl_2-treated$ MDCK cells. Conclusions: These results suggest that the activation of caspase-3 was involved in $HgCl_2-induced$ apoptosis. The release of cytochrome c from the mitochondria into the cytosol was also observed in the $HgCl_2-treated$ MDCK cells. These findings indicate that in MDCK cells, $HgCl_2$ is a potent inducer of apoptosis via cytochrome c release from the mitochondria.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• Journal of Gastric Cancer
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• v.3 no.3
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• pp.151-157
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• 2003

Purpose: In this study, we attempted to ascertain the proton magnetic resonance spectroscopy (${1}^H$ MRS) peak characteristics of human gastric tissue layers and finally to use the metabolic peaks of MRS to distinguish between normal and abnormal gastric specimens. Materials and Methods: Ex-vivo ${1}^H$ MRS examinations of thirty-five gastric specimens were performed to distinguish abnormal gastric tissues invaded by carcinoma cells from normal stomach-wall tissues. High-resolution 400-MHz (9.4-T) ${1}^H$ nuclear magnetic resonance (NMR) spectra of two gastric layers, a proper muscle layer, and a composite mucosasubmucosa layer were compared with those of clinical 64- MHz (1.5-T) MR spectra. Three-dimensional spoiled gradient recalled (SPGR) images were used to determine the size and the position of a voxel for MRS data collection. Results: For normal gastric tissue layers, the metabolite peaks of 400-MHz ${1}^H$ MRS were primarily found to be as follows: lipids at 0.9 ppm and 1.3 ppm; alanine at 1.58 ppm; N-acetyl neuraminic acid (sialic acid) at 2.03 ppm; and glutathione at 2.25 ppm in common. The broad and featureless featureless spectral peaks of the 64-MHz MRS were bunched near 0.9, 1.3, and 2.0, and 2.2 ppm in human specimens without respect to layers. In a specimen (Borrmmann type III) with a tubular adenocarcinoma, the resonance peaks were measured at 1.26, 1.36 and 3.22 ppm. All the peak intensities of the spectrum of the normal gastric tissue were reduced, but for gastric tumor tissue layers, the lactate peak split into 1.26 and 1.39 ppm, and the peak intensity of choline at 3.21 ppm was increased. Conclusion: We found that decreasing lipids, an increasing lactate peak that split into two peaks, 1.26 ppm and 1.36 ppm, and an increasing choline peak at 3.22 ppm were markers of tumor invasion into the gastric tissue layers. This study implies that MR spectroscopy can be a useful diagnostic tool for gastric cancer.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.548-553
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• 2010

Purpose : IgA nephropathy (IgAN) is the most commonly occurring form of chronic glomerulonephritis in pediatric cases. Human leukocyte antigen (HLA) genes have been implicated in various inflammatory and autoimmune diseases. The present study was conducted to investigate the association between 2 single nucleotide polymorphisms (SNPs) of the HLA-G gene and childhood IgAN. Methods : The authors analyzed and compared $HLA-G$ gene SNPs (rs1736936 and rs2735022) in 174 patients with childhood IgAN and in 438 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to proteinuria (< and >$4mg/m^2/hour$), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No significant SNP frequency differences were observed for the $HLA-G$ gene between IgAN patients and the control group. Moreover, no significantly associated SNP was observed with the presence of proteinuria, podocyte foot process effacement, or pathologically advanced markers. However, the haplotype, composed of rs1736936 and rs2735022, showed a significant association with the susceptibility to develop childhood IgAN (haplotype T/C: dominant model, $P$=0.049; haplotype C/T: recessive model, $P$=0.030). Conclusion : Our results indicate that rs1736936 and rs2735022 as the $HLA-G$ gene promoter haplotype might be associated with the susceptibility to develop childhood IgAN in the Korean population.