• Molecules and Cells
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• v.38 no.10
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• pp.851-858
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• 2015

Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.1
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• pp.76-81
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• 2016

Carnitine palmitoyltransferase 1A (CPT1A) is an enzyme functioning in mitochondrial fatty acid oxidation (FAO) of the liver. Patients with CPT1A deficiency have impaired mitochondrial FAO and display hypoketotic hypoglycemia and hepatic encephalopathy as typical manifestations. In this report, we present a case of CPT1A deficiency presenting jaundice as the first manifestation. A 1.9 years old boy showed jaundice and elevated levels of free and total carnitine were observed. From direct sequencing analysis of CPT1A, two novel mutations, c.1163+1G>A and c.1393G>A (p.Gly465Arg), were identified. At the age of 2.2 years, hypoglycemia, tachycardia, and altered mental status developed just after cranioplasty for craniosynostosis. High glucose infusion rate was required for recovery of his vital signs and mentality. Diet rich in high carbohydrate, low fat and inclusion of medium chain triglyceride oil resulted in improvement in cholestatic hepatitis and since then the boy has shown normal growth velocity and developmental milestones to date.

• Pediatric Infection and Vaccine
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• v.5 no.2
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• pp.230-238
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• 1998

Purpose : Worldwidely, the incidence of the hepatitis A has been markedly decreased in the past years. Also in Korea, there has been only a few sporadic cases without evidence of epidemics since the mid 1980s. However, the incidence of the hepatitis A in young adults and childen has been in trends of increasing since 1996. So, we retrospectively performed the study on the epidemiolgical changes and the clinical feature of hepatitis A in childen, living in Kyung-gi province, since 1988 to 1998. Methods : The four affiliated hospitals of the Catholic University of Korea, Our lady of Mercy's hospital, Holy family hospital, Eui-Jung-bu St. Mary's hospital, and St. Vincent hospital, were enrolled in this study. We conducted statistical analysis on the incidence of hepatitis A since 1988 to 1998, concerning with the period (monthly, annually), age, sex and related epidemiological property, by reviewing the hospital records of the patients with hepatitis A. We simultaneously performed the study concerning with the clinical characteristics of hepatitis A. Results : 1) During the study period, 46 children was diagnosed as hepatitis A, and among them 28 children (60.1%) developed sporadically in the 1998. And sex ratio was 1.2(male):1(female). 2) Most of the patients developed between March and July, and hepatitits A were mainly developed in the patients above the 10 year old ages(37 patients; 80.4%). 3) The socioeconomic and educational status of the patient's parents was almostly below the middle and low class. Although, we could not find the etiological factors in most cases, but we found the evidence of interfamilial transmission in one family. 4) The patients complained the symptoms of nausea and vomiting, jaundice, poor appetite, mild fever, fatigueness, abdominal pain, URI symptom, dyspepsia, dark urine, headache and diarrhea in order, and findings of jaundice, hepatomegaly, RUQ tenderness, splenomegaly and LLQ tenderness in order were seen. 5) All patients showed abnormal findings of the liver function tests, and the pattern of cholestatic hepatitis were seen in most cases, but these findings were normalized within the 2~4 weeks. The findings of the gall bladder wall thickening, hepatomegaly, splenomegaly and ascites were seen on abodominal sonogram. 6) The prognosis of all patients were good without complications, except in one case who had the episode of transient recuurence. And the mean hospitalization dates were 11.1 days. Conclusion : We found that the incidence of hepatitis A showed the increasing trend, and peaked in the 1998 in Kyung-gi province children. And hepatitis A mainly developed in children above the 10 year old ages. The scioeconomic and educational status of patient's family was almostly below the middle class. All of them showed abnormal liver function, and clinically cholestatic hepatitis features were seen in most cases. But, the prognosis was excellent without complication in all cases.

• Journal of Genetic Medicine
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• v.5 no.2
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• pp.131-135
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• 2008

Classical galactosemia is an autosomal recessive disorder of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). Buildup of galactose-1-phosphate is toxic at high levels and can damage the liver, brain, eyes, and other vital organs. The case presented here was that of an 11-day-old female infant who had elevated galatose levels upon initial neonatal screening test with persistent cholestatic jaundice, coagulopathy, and hepatomegaly. The patient was transferred due to aggravation of clinical symptoms including bleeding and jaundice. She had a delayed galactose free diet because of an inappropriate diagnosis. We quickly provided her with a lactose/galactose-restricted diet as per her final diagnosis. Clinical and laboratory results were improved after a few days of treatment. For confirmatory testing for classical galactosaemia, we simultaneously analyzed for GALT enzyme activity and allele-specific PCR/fragments for seven mutations and two polymorphisms in the GALT gene. We were able to find several GALT-deficient and compound heterozygous mutations of the GALT gene.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.186-190
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• 2014

Citrullinemia type 2 (citrin deficiency) is an autosomal recessive inborn error metabolism, caused by the SLC25A13 gene mutation. Citrin deficiency is associated with two clinical phenotype; neonatal-onset type II citrullinemia (CTLN2), also known as neonatal intraphepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset CTLN2. Clinical manifestations of NICCD include poor growth, intrahepatic cholestasis, liver dysfunction and increased plasma citrulline, methionine, threonine, arginine. The molecular diagnosis could be confirmed by SLC25A13 gene mutation analysis. A 3-month-old male infant with persistent jaundice was referred for evaluation. Newborn screening was normal at birth. Mild elevation of serum ammonia and AST/ALT were observed. Plasma amino acid analysis showed significantly elevated citrulline, methionine, threonine. DNA sequence analysis of the SLC25A13 gene revealed two compound heterozygous mutations, c.[852_855del]($p.Met285Profs^*2$) and [1180+1G>A]. We suggest that NICCD should be considered as one of the cause of in infants with cholestatic jaundice, although the newborn screening was normal.

• Journal of Life Science
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• v.21 no.12
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• pp.1772-1777
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• 2011

Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent $Cl^-/HCO_3^-$ anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.