A national project to build a business support facility for plant-derived vaccine

최보화,김도영 대한백신학회 2019 Clinical and Experimental Vaccine Research Vol.8 No.1

Controls of Nuclear Factor-Kappa B Signaling Activity by 5’-AMP-Activated Protein Kinase Activation With Examples in Human Bladder Cancer Cells

최보화,이다현,김진,강주희,박창신 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.3

Generally, both lipopolysaccharide (LPS)- and hypoxia-induced nuclear factor kappa B (NF-κB) effects are alleviated through differential posttranslational modification of NF-κB phosphorylation after pretreatment with 5´-AMP-activated protein kinase (AMPK) activators such as 5´-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or the hypoglycemic agent metformin. We found that AICAR or metformin acts as a regulator of LPS/NF-κB-or hypoxia/NF-κB-mediated cyclooxygenase induction by an AMPK-dependent mechanism with interactions between p65-NF-κB phosphorylation and acetylation, including in a human bladder cancer cell line (T24). In summary, we highlighted the regulatory interactions of AMPK activity on NF-κB induction, particularly in posttranslational phosphorylation and acetylation of NF-κB under inflammatory conditions or hypoxia environment.

신생아 담즙정체성 간질환에서 간조직 유전자의 발현 양상

최보화,최병호,정은정,김경모,김행미,박진영,박우현,김문규,김정철,Choi, BoHwa,Choe, Byung Ho,Chung, Eun Jung,Kim, Kyung Mo,Kim, Heng Mi,Park, Jin Young,Park, Woo Hyun,Kim, Moon Kyu,Kim, Jung Chul 대한소아소화기영양학회 2005 Pediatric gastroenterology, hepatology & nutrition Vol.8 No.2

목 적: 담즙정체를 보이는 환자의 간조직에서 cDNA microarray를 이용한 유전자 발현 분석을 통 하여 담도 폐쇄증의 발생과정에 관여하는 유전자를 규명하고자 연구를 시행하였다. 방 법: 환자의 간조직은 담즙정체를 보이는 11명의 환자로부터 진단적 간생검시 얻은 간조직의 일부를 이용하였다. 이들의 원인 질환은 담도 폐쇄증이 7명, 신생아 간염 증후군이 4명이었다. 정상대조군의 간조직은 생체부분 간이식시 성인 공여자로부터 얻은 간조직의 일부를 이용하였다. 간조직에서 분리된 mRNA를 4.7K 인간유전자 cDNA microarray를 이용하여 유전자 발현의 양상을 분석하였다. 결 과: 분석한 4,700종의 유전자 중 담즙정체 환자 11명 모두의 간조직에서 발현이 증가된 유전자는 17종이 발견되었고, 발현이 감소된 유전자는 20종이 발견되었다. 담도 폐쇄증 환자와 신생아 간염 증후군 환자 사이에 49종의 유전자에서 발현의 차이가 관찰되었고, 특히 담도 폐쇄증에서는 발현이 증가하였으나 신생아 간염 증후군에서는 발현이 감소된 유전자는 24종이었으며 이들 유전자 발현의 차이에 의해서 두 군간의 감별이 가능하였다. 결 론: 신생아 간질환에서 담도 폐쇄증 환자들은 모두 일정한 양상을 보여주어 이에 대한 분석을 통하여 담도 폐쇄증의 조기 감별 진단을 할 수 있을것을 시사하였다. 또한 담도 폐쇄증에서 특이 발현을 보이는 유전자의 추가적인 기능 연구를 시행함으로써 담도 폐쇄증의 원인을 규명하는데 도움을 줄 수 있을 것으로 생각한다. Purpose: To identify genes specifically expressed in biliary atresia, we compared the patterns of gene expression between biliary atresia and neonatal hepatitis syndrome using cDNA microarray analysis. Methods: Liver tissues were taken from livers of 11 patients (7 patients with biliary atresia and four with neonatal hepatitis) with neonatal cholestasis by needle biopsy. Normal control could be obtained from donor liver tissue during living-related liver transplantation. Total RNA was extracted from each samples and reversely transcribed to make cDNA. Then fluorescent cDNA were pooled and hybridized to the clones on the microarray. Fluorescence intensities at the immobilized targets were measured. Utilizing cDNA arrays of 4.7 K human genes, gene expression profiles were analyzed. Results: Among 4,700 microarray clones, 17 cDNA clones were significantly over-expressed in all 11 patients with neonatal cholestasis, while 20 clones were significantly decreased. Genome-wide expression analysis was carried out in livers obtained at the time of diagnosis. We could identify 49 genes, in which there showed differential expression between biliary atresia and neonatal hepatitis syndrome. Conclusion: This study shows the pattern of differentially expressed genes in biliary atresia and neonatal hepatitis syndrome. We believe that this study can contribute to the understanding of pathogenesis of neonatal cholestasis.

송과선에서 멜라토닌 합성과 분비조절

최보화,김경태 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.6

Effect of Anti-Siglec-F Antibody and Reactive Oxygen Species Blocking on Histamine Release in Urinary Bladder of Ovalbumin-Treated Mice

최보화,주관엽,강주희,이충열,박창신 대한배뇨장애요실금학회 2012 International Neurourology Journal Vol.16 No.3

Purpose: Sialic acid-binding Ig-like lectin (Siglec) is an immune inhibitory receptor that plays a role in the negative regulation of the activation of immune cells. This study aimed to evaluate the effects of anti-Siglec-F on plasma and urinary histamine levels in ovalbumin (OVA)-challenged urinary bladder in mice. Methods: Thirty BALB/c mice were used. In group I (control group, n=5), mice were sensitized with OVA and challenged with saline. In group II (OVA challenge group, n=5), OVA was used for intraperitoneal sensitization and intravesical challenge. The challenged mice in group III (control immunoglobulin G [IgG] group, n=5) and those in group IV (anti-Siglec-F group, n=5) were intraperitoneally pretreated with rabbit control IgG or anti-Siglec-F antibody, respectively. In groups V (N-acetylcysteine[NAC] in OVA challenge group, n=5) and VI (control NAC only, n=5), mice were pretreated with NAC. Results: Urinary histamine concentrations were significantly higher 7 days after intravesical OVA challenge (P<0.01), whereas plasma histamine levels were not. Pretreatment with anti-Siglec-F antibody significantly prevented the increase in urinary histamine release (P<0.05), whereas pretreatment with the IgG antibody control did not. Also, pretreatment of the OVA challenge group with NAC did not affect the histamine concentration in either urine or plasma. Conclusions: Systemic anti-Siglec-F treatment showed anti-allergic effects at least on local histamine release, particularly in the lower urinary bladder.

Intraventricular Anaplastic Hemangiopericytoma: CT and MR Imaging Findings

최보화,문진일,백혜진,조수범,배경수,전경녀 대한영상의학회 2016 대한영상의학회지 Vol.75 No.3

Intracranial hemangiopericytomas (HPC) are uncommon tumors, and their intraventricular occurrence is even rarer. Although the histopathologic findings in HPC are distinct, the diagnosis of intraventricular HPC can be difficult owing to its rarity and nonspecific clinicoradiologic manifestations. Here we present a case of intraventricular anaplastic HPC in a 20-year-old female patient, confirmed on histopathologic examination. We suggest that HPC should be considered in the differential diagnosis of space-occupying lesions of the ventricles. This article also highlights a situation in which clinical suspicion led to a meticulous radiologic review.

Leigh 증후군에서 생화학적 효소분석과 자기공명 분광검사(MR Spectroscopy)의 유용성에 관한 고찰

최보화(Bo Hwa Choi),김정호(Jeong Ho Kim),김현미(Hyun Mee Kim),최충곤(Choong Kon Choi),유한욱(Han Wook Yoo),고태성(Tae Sung Ko),Brian H. Robinson 대한소아신경학회 1998 대한소아신경학회지 Vol.5 No.2

목적 : Leigh 증후군은 lactate의 병적인 형성이 특징인 사립체성 질환으로서 뇌간, 뇌저 신경절, 시상, 소뇌 및 척수를 침범하여 여러 가지 다양한 임상증상을 나타내며 생화학적으로는 사립체내의 에너지 대사과정 중 pyruvate dehydrogenase complex 결핍, cytochrome c oxidase(complex Ⅳ) 결핍 등 여러 가지 효소의 결함에 의해서 초래될 수 있다. 이 질환은 괴사성 병변의 조직학적 소견으로 확진할 수 있으나, 특징적인 병변의 방사선학적 소견과 임상증상, 다른 질환을 배제함으로써 가능해졌다. 최근에는 생화학적 검사에 의한 효소의 결핍과 MR spectroscopy의 이용으로 좀더 정확한 진단에 도움을 주고 있다. 이에 저자들은 Leigh 증후군으로 진단된 환아에서 생화학적 효소분석과 MRS를 시행하여 이들의 유용성을 알아보고자 본 연구를 시행하였다. 방법 : 1992년 7월부터 1997년 6월까지 서울중앙병원 소아과에 입원하여 임상증상과 MRI 검사에서 Leigh 증후군으로 진단된 8명을 대상으로, 생화학적 효소분석(7명)은 섬유아 세포 배양후 캐나다의 Toronto 대학에 의뢰하였고, MRS는 본원에서 시행하여 각각 분석하였으며, 동시에 시행한 뇌척수액과 혈청에서의 lactate치, lactate/pyruvate률과 각각 비교하였다. 결과 : 1) 진단시 나이는 7개월에서 8년 11개월이었며, 남아가 7명 여아가 1명이었다. 2) 임상증성은 경련 6례(75%), 호흡 곤란, 안증상, 근긴장성 저하가 각각 4례(50%), 발달지연과 의식변화가 각각 3례(38%), 지능저하가 2례(25%) 등의 순으로 있었다. 3) MRI상 병변은 모두 양측에서 보였고, 부위별로는 피각 6례(75%), 미상핵 5례(63%), 연수 4례(50%), 흑질, 시상에서 각각 3례(38%) 등으로 보였다. 4)뇌척수액과 혈청에서 lactate치, lactate/pyruvate률이 증가한 2례에서는 생화학적 효소분석에서 NADH-coenzyme Q reductase(complex Ⅰ), cytochrome C oxidase(complex Ⅳ) 결핍을 각각 보였다. 5) 뇌척수액과 혈청에서 lactate치, lactate/pyruvate률이 정상인 6례에서는 발병후 4개월 이내에 시행한 MRS에서 전례에서 lactate 증가, NAA peak 감소를 보였다. 결론 : 생화학적 효소분석과 MRS Leigh 증후군에 있어서 진단적 가치가 매우 클 것으로 생각되며, 특히 MRS는 급성기 병의 활동성 판단에 도움을 줄 것으로 여겨진다. Purpose : Leigh syndrome is a kind of mitochondrial disease with a pathological production of lactate and variable clinical manifestations. Recently biochemical assay of the mitochondrial enzyme activity and MRS are becoming a powerful tool for the definitive antemorterm diagnosis of this disease. The aim of this study was designed to determine the usefulness of biochemical enzyme assay and MRS in Leigh syndrome. Methods : A clinical study of 8 cases of pediatric patients were diagnosed as Leigh syndrome on the basis of clinical manifestations and MRI features at the department of pediatrics, Ulsan university hospital, from July, 1992 to June, 1997. Biochemical enzyme assay of the cultured skin fibroblasts was consulted to hospital for sick children, Toronto, Canada. Cerebral lactates were detected on MRS were analysed in relation to the MRI findings and lactate levels in the CSF. Result : 1) Age at diagnosis ranged from 7 months to 8.9 years; seven were boys and one was girl. 2) Main clinical symptoms were as follows in the order of frequency; seizure(75%), ophthalmoplegia(50%), hemiplegia(50%), hypotonia(50%), respiratory difficulty(50%), developmental delay(38%), consciousness change(38%), mental retardation(25%). 3) Anatomical locations of the focal lesions detected on the initial MRI were as follows in the order of frequency; putamen(75%), caudate nuclei(63%), medulla oblongata(4/8, 50%), substantia nigra(38%), thalamus(38%). 4) Biochemical enzyme assay revealed deficiency of NADH cytochrome c reductase(complex Ⅰ) and dificiency of cytochrome c oxidase(complex Ⅳ) respectively in 2 patients who had markedly elevated serum and CSF lactate levels and lactate/pyruvate ratio 5) Cerebral lactates were detected by MRS from 6 lesions of 1 week-4 months old in 6 patients who had normal or mildly elevated serum and CSF lactate levels and lactate/pvruvate ratio. Conclusion : MRS detected the brain parenchymal lactate non-invasively from the acute or subacute lesions. Therefore, combined evaluation by MRS and biochemical enzyme assay will provide an important information for the diagnosis and estimation of disease activity in pediatric patients who are suspected to have Leigh syndrome.

Familial Juvenile Hyperuricemic Nephropathy 2례

박진호,최보화,이소영,유은실,박영서,Park Jin-Ho,Choi Bo-Hwa,Lee So-Young,Yoo Eun-Sil,Park Young-Seo 대한소아신장학회 1997 Childhood kidney diseases Vol.1 No.2

Familial juvenile hyperuricemic nephropathy is an autosomal dominant disease characterized by progressive renal disease and hyperuricemia or gout, affecting young people of either sex equally. There are two biochemical markers of this disorder. The first is hyperuricemia disproportionate to the degree of renal dysfunction; the second is a grossly reduced clearance of uric acid relative to creatinine, dispropotionate to age, sex and degree of renal failure. We experienced 2 family members with hyperuricemia. One family member, a 13-year-old girl who had suffered from tophaceous gout and chronic renal failure. Her younger brother also had hyperuricemia and moderately reduced renal function. Their urinary excretion fractions of uric acid($FE_{uric\;acid}$) were reduced and renal biopsy specimens showed interstitial fibrosis with tubular atrophy and interstitial urate crystal deposition. We have treated these two patients with allopurinol but we have done renal transplantation because she progressed to end stage renal disease at 16 year old age.

만성 B형 간염 환아에서 interferon-alpha 치료의반응 예측 인자 분석

김홍권,최보화,김경모,강경훈,임인석,최응상 대한소아청소년과학회 2000 Clinical and Experimental Pediatrics (CEP) Vol.43 No.4

Purpose : The efficacy and safety of interferon-alpha(IFN-■) therapy in children with chronic hepatitis B(CHB) is similar to that of adults. However, little information is available about the predictive factors of response to this therapy in children. The aim of this study was to determine the predictive factors for responsiveness to IFN-■ therapy in children with CHB. Methods : The basal parameters were studied in 35 children with CHB treated with IFN-■(300 MU/m2 of body surface area subcutaneously, 3 times weekly for 6 months). HBsAg, anti-HBs, HBeAg, anti-HBe, HBV DNA and aminotransferase levels were assessed serially. Pretreatment liver biopsies were performed in 16 patients and modified histologic activity index(HAI) was determined respectively. Responder was defined as disappearance of HBeAg and HBV-DNA after cessation of therapy. We analyzed the predictive factors of response to IFN-■ therapy. Results : Serum HBeAg and HBV DNA became negative in 16 children(46%) among 35 treated children at the time of cessation of therapy. In the univariate analysis, HAI, ALT level and maternal HBsAg were associated with the response. In multivariate analysis, HAI was the best factor for predicting response(sensitivity : 80% and specificity : 100%). Conclusion : Factors predictive of response in children with CHB are similar to those reported in adult, and may help identify those children with a better chance of responding. 목 적 : 소아에서도 성인과 같이 만성 B형 간염에 interferon(IFN)-α가 유용하다는 연구 결과들이 발표되고 있으나, 소아의 경우에 반응 예측 인자에 대해서는 아직 정립되어 있지 않다. 이에 본 연구에서는 소아 만성 B형 간염 환자에서 재조합 IFN-α 치료의 반응 예측 인자를 분석하여 보고자 하였다. 방 법 : 1992년 9월부터 1997년 7월까지 만성 B형 간염으로 진단받고 IFN-α로 치료받은 환아 35명을 대상으로 하였다. 대상 환아들의 연령은 2세에서 15세로 평균 12세 이었으며, 남아 28명, 여아가 7명이었다. 환아들의 치료 종료후의 평균 추적관찰 기간은 18개월이었다. IFN-α를 단위 체표면적당 300만 단위로 일주일에 3회씩 6개월간 피하 주사하였다. 16명에서 치료를 시작하기 전에 경피적 간생검을 시행하여 his- tologic activity index(HAI)를 확인하였고, 치료 전후의 B형 간염의 표지자, DNA값의 변화를 관찰하였다. 6개월 치료 뒤에 HBV DNA와 HBeAg의 음전을 보인 환아들을 반응군, 두 측정치의 음전이 관찰되지 않은 환아들을 무반응군으로 나누어 반응 인자를 분석하였다.

담도폐쇄증 진단에서 DISIDA 간담도주사의 진단적 의의

이병선,최보화,김경모,김재승,문대혁,Lee, Byeong-Seon,Choi, Bo-Hwa,Kim, Kyung-Mo,Kim, Jae-Seung,Moon, Dae-Hyeok 대한소아소화기영양학회 2000 Pediatric gastroenterology, hepatology & nutrition Vol.3 No.1

목 적: 신생아 담즙정체증의 흔한 원인중 하나인 담도폐쇄증의 진단에 많이 이용되고 있는 Tc-99m DISIDA간담도 주사의 진단적 의의에 대하여 알아보고자 하였다. 방 법: 1995년 1월부터 1999년 8월까지 4년 8개월 동안 서울 중앙병원 소아과와 소아외과에서 신생아담즙정체증으로 Tc-99m DISIDA간담도 주사를 시행한 60명의 환자를 대상으로 그 결과를 분석하였다. 결 과: 전체 60명의 환자 중에서 담도폐쇄증으로 14례(23%), 신생아 간염으로 33례(55%), 간내 담도형성부전증으로 9례(15%), 경정맥 고영양법으로 인한 황달로 4례(7%)가 진단되었다. Tc-99m DISIDA 간담도주사의 민감도는 100%를 보였고 특이도는 80%였다. 결 론: Tc-99m DISIDA 간담도주사에서 장관내 방사능이 관찰되면 담도폐쇄증을 진단에서 제외할 수 있지만 관찰되지 않을 경우에는 경피간침생검이나 시험적 개복술 등의 적극적인 진단방법을 고려해야 할 것으로 생각된다. Purpose: Biliary atresia, one of the major causes of neonatal cholestais, is an idiopathic, serious disorder, affecting the newborn that results in complete obstruction of biliary tract. Successful reestablishment of bile flow is dependent on early surgical intervention, early diagnosis is imperative. The authors evaluate the utility of Tc-99m-labeled diisoprpyliminodiacetic acid (DISIDA) hepatobiliary scintigraphy in the diagnosis of biliary atresia. Methods: From January, 1995 to August, 1999, total 60 patients with neonatal cholestasis underwent Tc-99m DISIDA hepatobiliary scintigraphy at Asan Medical Center. Results: The undelying causes of neonatal cholestasis were biliary atresia in 14, neonatal hepatitis in 33, intrahepatic bile duct paucity in 9, and total parenteral nutrition induced cholestasis in 4. All patient with biliary atresia were interpreted correctely in DISIDA hepatobiliary scintigraphy, showing 100% sensitivity. Of the 46 patients with neonatal hepatitis and other causes, 37 patients had intestinal radioactivity showing 80% specificity. Conclusion: Visualization of DISIDA in the intestinal tract indicates patency of the biliary ducts and excludes the diagnosis of biliary atresia. But the absence of intestinal excretion on the DISIDA hepatobiliary scintigraphy dose not necessarily indicate biliary atresia.