• 대한유전성대사질환학회지
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• 제1권1호
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• pp.23-27
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• 2001

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism recently demonstrated to be caused by mutations in the GLUT 2 gene for the glucose transporter protein 2 expressed in liver, pancreas, intestine, and kidney. This disease is characterized by hepatorenal glycogen accumulation, both fasting hypoglycemia as well as postprandial hyperglycemia and hyperglactosemia, and generalized proximal renal tubular dysfunctions. We report the first Korean patient with FBS diagnosed based on clinical manifestations and identification of a novel mutation in the GLUT 2 gene. She was initially diagnosed having a neonatal diabetes mellitus due to hyperglycemia and glycosuria at 3 days after birth. In addition, newborn screening for galactosemia revealed hypergalactosemia. Thereafter, she has been managed with lactose free milk, insulin therapy. However, she failed to grow and her liver has been progressively enlarging. Her liver functions were progressively deteriorated with increased prothrombin time. Liver biopsy done at age 9 months indicated micronodular cirrhosis with marked fatty changes. She succubmed to hepatic failiure with pneumonia at 10 months of age. Laboratory tests indicated she had generalized proximal renal tubular dysfuctions; renal tubular acidosis, hypophosphatemic rickets, and generalized aminoaciduria. Given aforementioned findings, the diagnosis of FBS was appreciated at age of 2 months. The DNA sequencing analysis of the GLUT 2 gene using her genomic DNA showed a novel mutation at 5th codon; Lysine5 Stop (K5X).

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제4권1호
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• pp.120-124
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• 2001

저자들은 복부 팽만과 지속적인 황달을 주소로 내원한 랑게르한스세포 조직구증 환아에서 간조직 검사 및 내시경적 역행성 담도조영술로 진단한 속발성 경화성 담관염 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Toxicological Research
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• 제25권1호
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• pp.23-28
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• 2009

Some of the edible plants like apricot kernel, flaxseed, and cassava generate hydrogen cyanide (HCN) when cyanogenic glycosides are hydrolyzed. Rhodanese (thiosulfate: cyanide sulfurtransferases of TSTs; EC: 2.8.1.1) is a sulfide-detoxifying enzymes that converts cyanides into thiocyanate and sulfite. This enzyme exists in a liver and kidneys in abundance. The present study is to evaluate the conversion of apricot cyanogenic glycosides into thiocyanate by human hepatic (HepG2) and colonal (HT-29) cells, and the induction of the enzymes in the rat. The effects of short term exposure of amygdalin to rats have also been investigated. Cytosolic, mitochondrial, and microsomal fractions from HepG2 and HT-29 cells and normal male Spraque-Dawley rats were used. When apricot kernel extract was used as substrate, the rhodanese activity in liver cells was higher than the activity in colon cells, both from established human cell line or animal tissue. The cytosolic fractions showed the highest rhodanese activity in all of the cells, exhibiting two to three times that of microsomal fractions. Moreover, the cell homogenates could metabolize apricot extract to thiocyanate suggesting cellular hydrolysis of cyanogenic glycoside to cyanide ion, followed by a sulfur transfer to thiocyanate. After the consumption of amygdalin for 14 days, growth of rats began to decrease relative to that of the control group though a significant change in thyroid has not been observed. The resulting data support the conversion to thiocyanate, which relate to the thyroid dysfunction caused by the chronic dietary intake of cyanide. Because Korean eats a lot of Brassicaceae vegetables such as Chinese cabbage and radish, the results of this study might indicate the involvement of rhodanese in prolonged exposure of cyanogenic glycosides.

• 한국어병학회지
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• 제36권2호
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• pp.415-422
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• 2023

In veterinary medicine for mammals, studies are being conducted to confirm the effects of antioxidants using pathological toxicity model studies, and are also used to confirm the effect of mitigating liver or kidney toxicity of specific substances. It was considered necessary to study such a toxicity model for domestic farmed fish, so thioacetamide (TAA), a toxic substance that causes tissue damage by mitochondrial dysfunction, was injected into rainbow trout (Oncorhynchus mykiss), a major farmed freshwater fish species in Korea. The experiment was conducted with 40 rainbow trout (Oncorhynchus mykiss) weighting 53 ± 0.6 g divided into two groups. Thioacetamide(TAA) 300mg/kg of body weight was intraperitoneally injected into rainbow trout and samples were taken 1, 3, 5, 7 days after peritoneal injection. As a result, in serum biochemical analysis, AST levels related to liver function decreased 3 and 5 days after intraperitoneal injection and increased after 7 days, and ALT levels also increased after 7 days. In addition, creatinine related to renal malfunction increased 3 and 5 days after TAA injection. In histopathological analysis, pericholangitis and local lymphocyte infiltration were observed in the liver from 1 day after intraperitoneal injection of TAA, and hepatic parenchymal cell necrosis was also observed from 3 days after intraperitoneal injection. Hyaline droplet in renal tubular epithelial cell was observed from 1 day after TAA injection, and acute tubular damage such as tubular epithelial cell necrosis appeared from 3 days after TAA injection. Accordingly, it is thought that it will be able to contribute to studies that require a toxicity model.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제7권1호
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• pp.61-73
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• 2004

목 적: 담즙울체를 포함한 간기능 이상은 총정맥영양법을 시행받는 환자에게서 자주 나타나는 합병증 중 하나이며 이를 해소하기 위한 방법의 하나로서 주기성 정맥영양법이 있으나 소아에서는 이에 대한 연구가 미흡한 상태이다. 본 연구에서는 소아에서 총정맥영양법의 합병증으로 생긴 간기능 이상의 발생초기에 주기성 정맥영양법을 시행하여 그 유용성을 평가하고자 하였다. 방 법: 연구대상은 미숙아를 제외한 유소아로 총정맥영양법에 의한 담즙울체 및 간효소치의 증가를 보이고 혈역학적, 대사적으로 안정되었으며 주기성 정맥영양법이 간기능 이상을 보이는 초기에 시도되었던 12례의 환아들이었다. 주기성 정맥영양법의 중단시간은 3개월 미만에서는 2시간 이하, 그 이상에서는 4시간으로 하였다. 환아들의 의무기록지를 후향적으로 검토하였고 진단명, 지속성과 주기성 정맥영양법의 시행기간과 방법, 대사성 혹은 감염성 합병증 유무, 병행된 경관영양유무 및 정맥영양법을 시행하기 전후의 혈청 총 빌리루빈과 간효소치의 변화를 비교하였다. 결 과: 1) 환아들의 정중연령(median age)은 주기성 정맥영양법 시작시 4세(생후 2개월에서 17세)였고 기저질환은 만성가성장폐색증 4례를 비롯하여 다양하였다. 2) 동일 예에서는 대부분에서 투여된 단백과 포도당, 지방의 투여량에 차이가 없었다(p<0.05). 주기성 정맥영양법을 시행하는 동안 1례에서 잘 조절되지 않는 고혈당이 나타나 포도당의 감량이 필요하였으나 다른 대사성 및 정맥관의 감염과 관련된 합병증은 없었다. 3) 혈청 총빌리루빈은 총 5례에서 상승하였고 주기성 정맥영양법 시행 후 전 증례에서 정상화되었다(p<0.05). 주기성으로 전환시 혈청 빌리루빈은 3.6 mg/dL였으며 정상화된 때까지 걸린 기간은 8일이었다. 4) AST/ALT의 상승은 12례에서 모두 관찰되었고 주기성 정맥영양법 시행 후 전례에서 정상화되었다. 주기성으로 전환시 혈청 ALT는 200 IU/L였으며 주기성 정맥영양 시행 후 정상화된 때까지 걸린 기간은 34일이었다. 결 론: 저자들은 장기간의 총정맥영양법으로 인해 발생한 간기능 이상을 보인 유소아에서 주기성 정맥영양법으로의 조기전환이 효과적인 치료적 대안이 될 수 있으며 부작용이 적은 안전한 방법임을 관찰하였다. 향후 주기성 정맥영양법은 총정맥영양을 시행받는 소아들에서 간기능 이상을 방지하고 삶의 질을 높이기 위한 일차적인 방법으로 더욱 연구되어야 할 것으로 생각된다.

• Neonatal Medicine
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• 제16권2호
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• pp.197-204
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• 2009

목 적 : 동일 병원에서 같은 기준에 의하여 정맥영양을 받는 미숙아들 중에도 간기능 검사 결과는 쓸개즙정체가 있는 경우와 없는 경우, 간효소의 수치만 오르고 쓸개즙정체의 증상이 없는 경우, 쓸개즙정체 및 간효소 수치의 이상이 없는 경우 등 서로 다른 것을 알 수 있다. 저자들은 출생 직후부터 정맥영양을 받은 미숙아 및 극소저출생체중아들을 대상으로 간기능 검사 결과의 양상 및 이에 영향을 미치는 요인을 알아보기 위하여 본 연구를 시행하였다. 방 법 : 2004년 1월 1일부터 2008년 12월 31일까지 가톨릭의대 부천 성모병원 신생아 집중치료실에 입원했던 출생체중 1,500 gm 미만의 미숙아들 중 2주 이상 TPN을 시행한 92명을 대상으로 이들의 의무 기록지를 후향적으로 검토하였다. 정맥영양 시행 2주 이후부터 관찰기간 동안 시행된 대상아 각각의 간기능 검사 전체를 분석하였으며 검사 결과 혈청 직접빌리루빈(direct bilirubin, DB) 2 mg/dL 이상이 측정되었고 담도폐쇄나 쓸개즙정체를 초래할 다른 원인이 배제된 경우 쓸개즙정체 그룹으로, aspartate aminotransferase (AST) 및 alanine aminotransferase (ALT)가 각각 60 IU/L 이상으로 측정되었고 측정시기에 상기의 제외기준을 비롯하여 뚜렷한 간손상의 원인을 알 수 없었던 경우 간세포손상 그룹으로 하였다. DB 2 mg/dL 이상인 쓸개즙정체그룹을 I군, DB 2 mg/dL 미만이나 AST 및 ALT가 각각 60 IU/L 이상인 간효소치 이상군을 II군, 각각에 이상이 없었던 정상군을 III군으로 하였다. 각 대상아들의 출생체중, 재태주령, 분만방법, 당뇨병 및 전자간증 등의 산모질환, 1분 및 5분 아프가 점수, 계면활성제 사용, 장관영양 시작 시기, 정맥영양기간, 적혈구수혈 횟수, 패혈증, 괴사성장염, 만성호흡곤란증, 동맥관개존증 발생 등을 비교하였다. 결 과 : 대상아들 중 쓸개즙정체 그룹이 36명(39.1%), 간세포손상 그룹이 51명(55.4%) 이었으며, I군 36명(39.1%), II군 19명(20.7%), III군 37명(40.2%) 이었다. 쓸개즙정체그룹과 간세포손상 그룹 각각에 대한 T검정 및 교차분석 결과 재태일령, 출생체중, 1분 및 5분 아프가 점수, 정맥영양기간, 적혈구수혈 횟수, 계면활성제 사용, BPD 진단, PDA 진단 유무에서 유의한 상관관계를 보였다(P<0.05). 쓸개즙정체 그룹을 종속변수로 한 다중회귀분석결과 재태주령, 계면활성제 사용, 패혈증, 적혈구수혈 횟수, 동맥관 개존증과의 관계가 유의했다(P<0.05). 결 론 : 정맥영양을 받고 있는 극소저출생체중아의 쓸개즙정체증에 대하여 정맥영양 이외에 출생체중, 재태주령, 1분 및 5분 아프가 점수, 계면활성제사용, 적혈구수혈 횟수, 만성호흡곤란증, 동맥관개존증 등 요인들에 대한 고민이 동반 되어야 할 것으로 생각된다.

• BMB Reports
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• 제45권10호
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• pp.554-559
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• 2012

Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), a glycosyltransferase encoded by the Mgat5 gene that catalyzes the formation of ${\beta}1$,6GlcNAc (N-acetylglucosamine) branches on N-glycans, is thought to be associated with cancer growth and metastasis. Overexpression of GnT-V in cancer cells enhances the signaling of growth factors such as epidermal growth factor by increasing galectin-3 binding to polylactosamine structures on receptor N-glycans. In contrast, GnT-V deficient mice are born healthy and lack ${\beta}1$,6GlcNAc branches on N-glycans, but develop immunological disorders due to T-cell dysfunction at 12-20 months of age. We have developed Mgat5 transgenic (Tg) mice (GnT-V Tg mice) using a ${\beta}$-actin promoter and found characteristic phenotypes in skin, liver, and T cells in the mice. Although the GnT-V Tg mice do not develop spontaneous cancers in any organs, there are differences in the response to external stimuli between wild-type and GnT-V Tg mice. These changes are similar to those seen in cancer progression but are unexpected in some aspects. In this review, we summarize what is known about GnT-V functions in skin and liver cells as a means to understand the physiological roles of GnT-V in mice.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제10권1호
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• pp.60-65
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• 2007

저자들은 가족 내에서 아동학대로 인해 발생한 치명적인 중증 영양실조를 보인 5세 여아에 동반된 빈혈과 구리 결핍증을 WHO 치료 지침과 구리 보충요법으로 호전시킨 1예를 치험하였기에 보고하는 바이다.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.306-311
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• 2008

Although hepatic microcirculatory dysfunction occurs during endotoxemia, the mechanism responsible for this remains unclear. Since Kupffer cells provide signals that regulate hepatic response in inflammation, this study was designed to investigate the role of Kupffer cells in the imbalance in the expression of vasoactive mediators. Endotoxemia was induced by intraperitoneal E. coli endotoxin (LPS, 1 mg/kg body weight). Kupffer cells were inactivated with gadolinium chloride ($GdCl_3$, 7.5 mg/kg body weight, intravenously) 2 days prior to LPS exposure. Liver samples were taken 6 h following LPS exposure for RT-PCR analysis of mRNA for genes of interest: endothelin (ET-1), its receptors $ET_A$ and $ET_B$, inducible nitric oxide synthase (iNOS), heme oxygenase (HO-1), and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). mRNA levels for iNOS and TNF-$\alpha$ were significantly increased 31.8-fold and 26.7-fold in LPS-treated animals, respectively. This increase was markedly attenuated by $GdCl_3$, HO-1 expression significantly increased in LPS-treated animals, with no significant difference between saline and $GdCl_3$ groups. ET-1 was increased by LPS. mRNA levels for $ET_A$ receptor showed no change, whereas $ET_B$ transcripts increased in LPS-treated animals. The increase in $ET_B$ transcripts was potentiated by $GdCl_3$. We conclude that activation of Kupffer cells plays an important role in the imbalanced hepatic vasoregulatory gene expression induced by endotoxin.

• Journal of Community Nutrition
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• 제7권3호
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• pp.163-168
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• 2005

The present investigation was undertaken in vivo to determine whether the functional alterations of hepatic mitochondria induced by ethanol might be prevented by taurine. We examined the effects of supplementation of taurine on hepatic mitochondrial oxidative phosphorylation in the chronic ethanol-administered rats. Isolated hepatic mitochondria from three groups of rats were functionally tested by an analysis of $\beta-hydroxbutyrate-supported$ respiration and the coupling of this process to ATP synthesis in the presence of ADP. The three groups were control group(CO), ethanol(60g/L) administered group (AL), and ethanol (60g/L) + taurine (5g/L) supplemented group (AT). Ethanol and/or taurine were given in drinking water for 10 weeks. The mitochondria from AL group had lower state 4 respiratory rate, respiratory control (RC) ratio and ADP : O(P/O) ratio than those from CO and AT group. It showed that the ethanol administered rats were less coupled and thus less efficient with respect to mitochondrial ATP synthesis than both control rats and ethanol + taurine supplemented rats. It suggests that taurine supplementation might improve the impaired oxidative phosphorylation efficiency in mitochondrial dysfunction that is recognized as a cause of liver diseases in chronic ethanol consumption.