Plasmaphresis therapy for pulmonary hemorrhage in a pediatric patient with IgA nephropathy

임대균,이상택,조희연 대한소아청소년과학회 2015 Clinical and Experimental Pediatrics (CEP) Vol.58 No.10

IgA nephropathy usually presents as asymptomatic microscopic hematuria or proteinuria or episodic gross hematuria after upper respiratory infection. It is an uncommon cause of end-stage renal failure in childhood. Pulmonary hemorrhage associated with IgA nephropathy is an unusual life-threatening mani- festation in pediatric patients and is usually treated with aggressive immunosuppression. Pulmonary hemorrhage and renal failure usually occur concurrently, and the pulmonary manifestation is believed to be caused by the same immune process. We present the case of a 14-year-old patient with IgA nephropathy who had already progressed to end-stage renal failure in spite of immunosuppression and presented with pulmonary hemorrhage during oral prednisone treatment. His lung disease was com- parable to diffuse alveolar hemorrhage and was successfully treated with plasmapheresis followed by oral prednisone. This case suggests that pulmonary hemorrhage may develop independently of renal manifestation, and that plasmapheresis should be considered as adjunctive therapy to immunosup- pressive medication for treating IgA nephropathy with pulmonary hemorrhage.

Application of 13C MFA for microbial GABA production

임대균,오민규 한국공업화학회 2018 한국공업화학회 연구논문 초록집 Vol.2018 No.1

Stretchable pressure sensitive adhesives with high adhesive performance and optically clearance for flexible electronics

임대균,백명진,김학선,백충기,이동욱 한국공업화학회 2021 한국공업화학회 연구논문 초록집 Vol.2021 No.-

정부출연 연구기관의 연구개발 생산성 변화 분석

임대균,이한규,김문수 대한산업공학회 2009 대한산업공학회 추계학술대회논문집 Vol.2009 No.10

본 연구는 산업응용기술분야 7개 연구기관의 2003~2008년 6개년도 자료를 대상으로 상대적 효율성 평가 기법인 DEA을 적용하여 연구개발 생산성 변화를 고찰한다. 분석 대상 기관의 제한적인 수에 따른 DEA 적용 한계를 극복 하기 위해서 AHP 방법을 활용하여 DEA 모형의 가중치에 대한 제약조건을 부가하였으며, 또한 각 연구기관별 연구개발생산성에 대한 동태적 변화 분석을 위해서 맘퀴스트 생산성지수를 산출하여 기관별, 시기별 비교 분석하고 이를 통해 정책적 시사점을 파악하였다.

Microbial GABA Production via Metabolic Engineering with ¹³C MFA

임대균,구본철,오민규 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0

We engineered E.coli to synthesize GABA through knocking out byproduct pathway related genes and overexpressing modified glutamate decarboxylase which can synthesize GABA under neutral pH condition. However, as the titer of GABA was still low, ¹³C MFA was conducted to determine metabolic flux ratios of central carbon metabolism to identify metabolic bottleneck for GABA production. From ¹³C MFA result, intracellular metabolic flux ratios were successively quantified and rational metabolic engineering targets were determined. We enhanced anaplerotic flux by introducing heterologous pyruvate carboxylase from C. glutamicum and additionally down regulated TCA flux by knocking out sucA to reduce byproduct secretion by succinate. Finally, ¹³C MFA was carried out to verify optimal central carbon metabolic flux ratios for GABA production. Engineered E.coli strain synthesize 1.8 g/L of GABA in defined medium condition.

Investigation of metabolic reprograming in CK2α-overexpressed colon cancer cells by carbon isotope using GC/MS

임대균,양경미,정희선,이종석,오민규 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0

CK2α is a serine/threonine kinase that is constitutively active in multiple cancer cells. Using colon cancer cell lines such as HT29 and SW620, CK2α induced epithelial mesenchymal transition and the transitioned cells became more proliferative. We assumed that CK2α could affect cancer cell growth by modulating energy metabolism. Therefore, we examined the reprogrammed metabolic fluxes of CK2α on glucose metabolism via isotope labeled substrates and could successfully determine the relative amount and mass isotopomer distribution(MID) of metabolites using GC/MS. The results showed that continuous activation of CK2α facilitates the Warburg effect and anaplerotic pathway. Besides, results also showed CK2α overexpression affected glutamine uptake metabolism, varying amount and MID of TCA intermediates. This study suggests that because oncogenes regulate important metabolic enzymes and metabolism signaling pathways, CK2α is an excellent metabolic target for cancer therapy.

Comparison of metabolite profiling of Ralstonia eutropha H16 phaBCA mutants grown on different carbon sources

임대균,윤석훈,정준영,이진원,오민규 한국화학공학회 2017 Korean Journal of Chemical Engineering Vol.34 No.3

Metabolite profiling was conducted to monitor the metabolic differences of the Ralstonia eutropha H16, polyhydroxybutyrate (PHB) producing strain, when grown on different sole carbon sources and to identify the effect of the deletion of the PHB production pathway. The combination of rapid filtration and boiling ethanol extraction successfully extracted intracellular metabolites. Accumulation of acetyl-CoA was detected when the strain was grown on fructose. Whereas, lower adenylate energy charge (AEC) ratio and cell mass was identified on the cells grown on acetate. No significant difference was detected between the wild type and mutant strain except metabolites in the PHB synthetic pathway. Increased PHB production is expected on fructose due to the accumulation of AcCoA, while it is more difficult to improve the production on acetate because of lower metabolic precursor level and AEC ratio.

ASS 1 유전자 돌연변이로 확진된 시트룰린혈증 1형 1례

임대균,허림,권영희,이지은,조성윤,박형두,진동규,Yim, Dae kyoon,Huh, Rimm,Kwun, Younghee,Lee, Jieun,Cho, Sung Yoon,Park, Hyung Doo,Jin, Dong-Kyu 대한유전성대사질환학회 2015 대한유전성대사질환학회지 Vol.15 No.1

시트룰린혈증은 유전적인 요인에 의하여 혈중에 암모니아를 비롯한 독성 물질이 축적되어 치명적인 임상 경과를 나타낼 수 있는 질환이다. 이 질환은 2가지 형태로 구분할 수 있으며, 유형별로 각기 다른 원인과 임상 양상을 보이는 것으로 알려져 있다. 시트룰린혈증 1형은 상염색체 열성유전 질환으로 암모니아를 간에서 요소로 합성하는 과정에 아르기니노숙신 생성효소(argininosuccinate synthethase)가 결핍되어 혈중 암모니아 농도와 혈중 시트룰린 농도의 증가와 혈중 아르기닌의 저하를 초래하게 되는 질환이다. 시트룰린혈증의 유병률은 50,000-60,000명당 1명 정도이다. 시트룰린 혈증은 임상 양상과 분자유전학적 특징에 따라 2가지 유형으로 구분할 수 있는데, 1형은 급성으로 신생아기에 발병하는 가장 흔한 형태이다. 환자는 출생시에는 특별한 증상을 보이지 않다가, 생후 3-4일을 지나면서 구토, 기면, 발작을 나타내게 되며 심하면 혼수 및 사망까지 이를 수 있다. 한편, 발병이 늦은 경우는 보다 드문 형태로 임상적으로 비교적 경한 증상을 나타낸다. 시트룰린혈증 1형은 9q34.1 염색체에 위치한 ASS1 유전자의 돌연변이에 의하여 아르기니노숙신 생성효소가 결핍되어 나타나며, 이 효소는 요소 회로에서 시트룰린과 아스파르트산이 아르기니노숙신으로 전환되는 과정을 담당한다. 따라서 ASS1 유전자의 돌연변이를 규명하는 것은 이 질병을 진단하는 데 분자유전학적으로 가장 확실한 방법이다. 저자들은 의심 증상을 가진 환자에게 조기에 시트룰린혈증 1형을 유전자 분석을 통하여 진단하였으며, 지속적 신대체 요법을 포함한 효과적인 급성기 치료 과정을 거쳐 현재 장기적인 식이 및 약물 치료를 성공적으로 진행 중에 있어, 이를 문헌 고찰과 함께 보고하는 바이다. Citrullinemia type1 is an autosomal recessive disorder of the urea cycle characterized by neonatal or late onset of hyperammonemia caused by a deficiency of the enzyme argininosuccinate synthetase (ASS). An ASS1 deficiency demonstrates fatal clinical manifestations that are characterized by the neonatal metabolic coma and early death when untreated. It causes a broad spectrum of effects, ranging from a mild disorder to a severe mental retardation, epilepsy, neurologic deficits. An acute neonatal form is the most common. Infants are normal at birth followed by an acute illness characterized by vomiting, lethargy, seizures and coma. These medical problems are life-threatening in many cases. A later onset form is less frequent and may be milder than the neonatal form. This later-onset form is associated with severe headaches, visual dysfunction, motor dysfunction, and lack of energy. Citrullinemia type1 is caused by mutations in the ASS1 gene located on chromosome 9q34.1 that encodes argininosuccinate synthetase, the third enzyme of the urea cycle catalyzing the formation of argininosuccinic acid from citrulline and aspartic acid. The enzyme is distributed in tissues including liver and fibroblasts. This mutation leads to hyperammonemia, arginine deficiency and elevated citrulline level. In the urea cycle, argininosuccinate synthetase catalyses the conversion of citrulline and aspartate to argininosuccinate.. Here, we describe a female newborn patient with lethargy, rigidity and hyperammonemia who was diagnosed as citrullinemia type1 with a c.[421-2A>G], c.[1128-6_1188dup] mutation.

GABA Production from glucose in E.coli with 13C MFA

이보영,임대균,오민규 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1

We engineered E.coli to synthesize GABA through knocking out byproduct pathway related genes and overexpressing modified glutamate decarboxylase which can synthesize GABA under neutral pH condition. However, as the titer of GABA was still low, 13C MFA was conducted to determine metabolic flux ratios of central carbon metabolism to identify metabolic bottleneck for GABA production. From 13C MFA result, intracellular metabolic flux ratios were successively quantified and rational metabolic engineering targets were determined. We enhanced anaplerotic flux by introducing heterologous pyruvate carboxylase from C. glutamicum and additionally down regulated TCA flux by knocking out sucA to reduce byproduct secretion by succinate. Finally, 13C MFA was carried out to verify optimal central carbon metabolic flux ratios for GABA production. Engineered E.coli strain synthesize 2 g/L of GABA in defined medium condition. This is the first report on GABA synthesis from defined medium condition.

Improved isoprenoids production by precursor rebalancing using precise control of gapA expression in Escherichia coli

우성화,임대균,석주연,오민규,정규열 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1

Biosynthesis of isoprenoids via the DXP pathway requires equimolar glyceraldehyde 3-phosphate and pyruvate to divert carbon flux toward the products of interest. Here, we demonstrate that precursor balancing is one of the critical steps for the production of isoprenoids in E. coli. First, the implementation of the synthetic lycopene production pathway as a model system and the amplification of the native DXP pathway were accomplished using synthetic promoters and redesigned 5'-UTR. Next, fine-controlled precursor balancing was investigated by tuning phosphoenolpyruvate synthase (PpsA) or glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The results showed that tuning-down of gapA improved the specific lycopene content by 46% compared to the overexpression of ppsA. The lycopene in the strains with down-regulated gapA increased by 96% compared to that in the parental strain. Our results indicate that gapA is the best target for precursor balancing to increase biosynthesis of isoprenoids.