• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.48-53
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• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• Clinical and Experimental Pediatrics
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• v.46 no.1
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• pp.86-90
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• 2003

Alagille syndrome is a autosomal dominant disorder characterized by intrahepatic bile duct paucity and resultant chronic cholestasis in combination with cardiac(mainly peripheral pulmonary stenosis), skeletal, ocular, and facial abnormalities. In addition to the pulmonary stenosis, in large series, anecdotal reports of vascular lesions have concerned the renal artery, aorta, hepatic artery, carotid artery, celiac artery or subclavian artery. Theses diffuse vascular abnormalities, which appear to be a feature of Alagille syndrome, suggest Notch signaling pathway defects affect angiogenesis. The associations of Alagille syndrome with moyamoya disease, the chronic cerebrovascular occlusive disease, were reported and suggested as additional evidence of vasculopathy of Alagille syndrome. We report another 25 month-old Alagille syndrome girl who presented with acute left hemiparesis and was diagnosed with moyamoya disease through the cerebral angiographic study.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.96-107
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• 2006

Citrin deficiency resulting from mutations of SLC25A13is associated with two major clinical phenotypes; neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type 2 citrullinemia (CTLN2). In Korea, 7 cases of citrin deficiency have been diagnosed based on biochemical and molecular findings. Four NICCD cases were identified by newborn screening using MS/MS or presenting symptoms like cholestatic jaundice. They are all males, presenting with conjugated hyperbilirubinemia, elevated liver enzymes, hypoalbuminemia, mild hyperammonemia, elevated citrullin, methionine and threonine. All of them have been spontaneously recovered from hepatic manifestation by the age of 6-8 months. Mutation analysis has been performed using their genomic & cDNAs obtained from skin fibroblasts. They turned out to be compound heterozygotes carrying each of 851del4, IVS11+1G>A, and IVS13+1G>A. Three CTLN2 patients were identified. Two adult male patients presented with a sudden loss of consciousness, seizure, vomiting, hyperammonemia and citrullinemia in their twenties. They carried an IVS13+1G>A, 851del4, and IVS11+1G>A mutant alleles. The other CTLN2 patient was 52 year old female patient, manifesting lethargy, altered consciousness, irritability and hyperammonemia. Similar clinical symptoms had recurred at the delivery of first and second babies in her past medical history. She was managed by hemodialysis and survived with neurological sequellae. Also, we screened the presence of 9 common mutations in 500 Korean newborns using dried blood spot of filter papers. Only a allele carried 854del4 mutation. In conclusion, the entire picture of citrin deficiency in Korea including incidence, genotype, clinical features and natural courses, is still vague at the present time.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.546-550
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• 2005

Sarcoidosis is a rare systemic disorder with unknown cause that is characterized pathologically by non-caseating granuloma. The lung and mediastinal lymph nodes are almost always involved, and most patients experience acute or insidious respiratory symptom. Because sarcoidosis is an interstitial lung disorder involving the alveoli and bronchioles, the most common radiological finding is a reticularnodular lesion with lymphatic distribution. However, cavitation is quite rare. Sarcoidosis is also a major cause of hepatic granuloma in Western countries, accounting for 12% to 30% of cases. In most patients, the course of hepatic sarcoidosis is benign. However, chronic intrahepatic cholestasis or portal hypertension may develop in some patients. We report a case of sarcoidosis with cavitation and hepatic involvement.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.69-76
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• 2017

Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene on chromosome 7q21.3, and a type of urea cycle disorder that causes hyperammonemia. Although neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, a type of citrin deficiency, have been described well in many articles for several decades, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), the other type of citrin deficiency, has been only identified recently. There was previously no case report about FTTDCD in Korea. Patients with FTTDCD could present with loss of appetite, fatigue, failure to thrive, hypoglycemia, hypercitrullinemia, dyslipidemia, and an increased lactate/pyruvate ratio. Routine evaluation may not reveal the cause of hypoglycemia caused by citrin deficiency. We recently had a case that presented with recurrent hypoglycemia in a 30-month-old boy. Chemistry profiling, urine organic acid analysis, plasma acylcarnitine analysis, and hormone studies indicated values within the normal range or non-specific findings. Mutation analysis to identify the cause of hypoglycemia identified the subject as a compound heterozygote carrying each of the c.852_855del ($p.Met285Profs^*2$), and c.1177+1G>A mutant alleles. We report here on this unusual case of citrin deficiency presenting with FTTDCD for the first time in Korea.

• Gut and Liver
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• v.12 no.6
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• pp.722-727
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• 2018

Background/Aims: Although endoscopic bilateral stent-instent placement is challenging, many recent studies have reported promising outcomes regarding technical success and endoscopic re-intervention. This study aimed to evaluate the technical accessibility of stent-in-stent placement using large cell-type stents in patients with inoperable malignant hilar biliary obstruction. Methods: Forty-three patients with inoperable malignant hilar biliary obstruction from four academic centers were prospectively enrolled from March 2013 to June 2015. Results: Bilateral stent-in-stent placement using two large cell-type stents was successfully performed in 88.4% of the patients (38/43). In four of the five cases with technical failure, the delivery sheath of the second stent became caught in the hook-cross-type vertex of the large cell of the first stent, and subsequent attempts to pass a guidewire and stent assembly through the mesh failed. Functional success was achieved in all cases of technical success. Stent occlusion occurred in 63.2% of the patients (24/38), with a median patient survival of 300 days. The median stent patency was 198 days. The stent patency rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months postoperatively, respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10 underwent percutaneous drainage. Conclusions: Large cell-type stents for endoscopic bilateral stent-in-stent placement had acceptable functional success and stent patency when technically successful. However, the technical difficulty associated with the entanglement of the second stent delivery sheath in the hook-cross-type vertex of the first stent may preclude large cell-type stents from being considered as a dedicated standard tool for stent-in-stent placement.