화살나무의 항종양작용과 그 기전

이정호,김학군,하대유 大韓免疫學會 1993 大韓免疫學會誌 Vol.15 No.-

The water extract of sprig of winged euonymus(Euonymus alatus, EA) has been used for curing gastric ulcer and stomach cancer as a folk medicine without any kind of experimental evidence to support the rationales for its clinical use. This experiment was carried out to evaluate the possible prophylactic or therapeutic effect of EA-extract against cancer. Some kind of tumors were induced by the topical application of 3-Methylcholanthrene(MCA) or by the implantation(sc) of malignant tumor cells such as Lewis lung carcinoma cells(3LL cells) or sarcoma cells(S-180 and Fsa2 cells). EA-application(daily 1mg/mouse, ip) was initiated 7 days prior to tumor-induction and lasted for 20 days. Against squamous cell carcinoma induced by MCA, EA decreased not only the frequency of tumor-induction but also the number and weight of tumors per tumor bearing mice(TBM). EA also significantly suppressed the development of 3LL cell and S-180 cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous administration of EA to TBM. However, when tumor was induced by Fsa2 cell-implantation, the growth of implanted cells in mice was delayed by EA until day 7 and then rapid growth ensued. In vitro EA had no effect on the growth of Fsa2 and A431 cells but it also significantly inhibited the proliferation of 3LL and S-180 tumor cells. EA-administration into mice enhanced Arthus reaction, delayed hypersensitivity and antibody production to sheep erythrocytes. It augmented the DNA synthesis of mitogen-activated lymphocytes and NK cell activities. It stimulated the production of IL-2 and migration inhibitory factor of T cells, but not IL-6 secretion of B cells. These results demonstrated that EA exhibited a significant prophylactic and therapeutic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested the mechanisms responsible for the anticancer effect of EA might be chiefly due to nonspecific enhancement of the NK cell activities and the cell-mediated immune responses.

제주 지역의 B형 간염 바이러스 유전자형

조지현,박도심,김태현,염주진,김학철,문주현,양재식 대한간학회 2004 Clinical and Molecular Hepatology(대한간학회지) Vol.10 No.1

목적: HBV 감염이 무증상의 자연 회복부터 간경변 혹은 간세포성 간암까지 다양하게 나타나는 요인들로 숙주의 요인과 바이러스의 요인으로 구분되어 제시되는데, 바이러스 요인으로는 감염된 바이러스이 유형이나 염기 변이들이 논의된다. HBV 유형을 구분하는 데는 혈청형과 유전자형이 이용되는데 근자에는 주로 유전자형이 이용된다. 이러한 HBV의 분포는 지역적으로 다르나 지역에 따라서 다른 유형들이 혼재되어 있다. 동남아시아는 B형이지만 극동아시아는 C형으로 알려져 있으며, 대만과 오키나와에서는 B와 C형이 혼재되어 나타난다. 이러한 결과로 미루어 보아 우리 나라의 남부지역에서는 B과 C형이 혼재되어 있을 가능성이 있다. 이에 본 연구는 제주 지역에서 HBV의 유전자형을 조사하고자 하였다. 대상과 방법: 원적지가 제주도이면사, HBsAg가 양성이었던 107명(평균 연령: 46.5세)을 대상으로 하였다. 이들의 혈청으로부터 HBsAg/antiHBe를 분석하고, DNA를 추출하여 7개의 유전자형에 따라 특이성을 갖는 시발체(genotype specific primer)들을 이용하여 PCR로 증폭한 후 이를 분석하였다. 주된 유전자형의 일부와 다른 유형에서 증폭에 이용되었던 시발체를 다르게 이용하여 hemi nested PCR로 증폭한 후 염기를 분석하여 계통발생학적 분석법을 이용하였다. 결과: 1. PCR에 의한 HBV DNA 양성은 107명 중 59명(55.1%)이 양성이었다. HBeAg/anti HBe의 발현 양태에 따라 음성/음성에서 2명(66.7%), 음성/양성에서 30명(41.1%), 양성/음성에서 24명(85.7%), 양성/양성에서는 3명(100%)에서 증폭되었다. 2. Multiplex PCR에서는 58명의 유전자형이 C형, 1명에서는 B형과 C형이 동반 출현하였다. 3. Genotype specific primer를 이용하여 각각 따로 PCR을 시행한 경우에 A형에 의하여 증폭된 예가 1예, B형에 의하여 증폭된 예가 1예, C형에 의하여 증폭된 예가 59예로 A형과 B형 모두가 C형에서 증폭된 예였다. 4. 한 쌍의 시발체에 의하여 증폭되었던 A형과 B형 및 C형의 일부에서 염기를 분석한 결과 모두 C 유전자형이었다. 결론: HBsAg이 양성인 제주 지역 주민의 HBV의 유전자형은 C형일 것으로 생각된다. Background/Aims: Hepatitis B virus (HBV) was classified into 8 genotypes by a sequence divergence in the entire genome designated from A o H. HBV genotypes have distinct geographic distributions. Recently, HBV genotypes have been partially found as influencing the clinical manifestation of chronic liver disease in hosts. In Korea, the distribution of HBV genotypes remains unclear. The aim of this study was to evaluate the prevalence of the HBV genotype on Jeju Island. Methods: Hepatitis B virus genotypes were evaluated among 107 hepatitis B carriers residing on Jeju Island. We used single PCR and multiplex-PCR assay with genotype-specific primer pairs for HBV genotypes A-F for the genotyping. Results: 1. Fifty nine samples (55%) were positive for HBV DNA. The positivity was different according to the pattern of HBeAg/anti-HBe expression, as -/-; 2/3 (66.7%), -/+; 30/73 (30%), +/-; 24/28 (85.7%) and +/+; 3/3 (100%). 2. In the single primer set of genotype-specific PCR, 59 samples (100%) were detected as genotype C and 2 (3%) were also detected as genotype A and B. 3. In multiplex-PCR, 58 samples (98%) were detected as genotype C and only one (2%) as a mixed pattern of genotype B and C. 4. When the PCR products were amplified with universal sense and genotype specific anti-sense from one genotype A, one B, and 2 C, all were included in genotype C. Conclusions: These results suggest that on Juju Island, almost all HBV genotypes are C.(Korean J Hepatol 2004;10:42-50)

전형적인 DISIDA scan 소견의 Rotor 증후군 1예

황의태,염동한,권지혜,임종주,최창수,김태현,김학철 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.2

만성의 비용혈성 직접형 고빌리루빈혈증은 Rotor 증후군과 Dubin-Johnson 증후군의 특징적인 소견으로, Rotor 증후군은 드문 양성 유전성 질환이며, Dubin-Johnson 증후군과 감별을 필요로 한다. 본 저자들은 황달을 주소로 내원한 26세 남자 환자에서 고빌리루빈혈증에 대한 검사를 시행하여 담도폐쇄 소견없이 간담도 스캔상 전형적인 Rotor 증후군의 소견 즉, 강한 심장 배후방사능이 지속되면서, 간담도계의 조영은 지연 촬영에서도 관찰되지 않으며 신장으로의 배설이 계속 관찰되는 특징적인 소견과 정상 간조직 검사 결과로 Rotor 증후군으로 진단한 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다. Chronic nonhemolytic conjugated hyperbilirubinemia characterizes both Rotor and Dubin-Johnson syndromes. Rotor syndrome is a rare, benign familial disorder and needs to be differentiated from Dubin-Johnson syndrome. Cholescintigraphy is a simple and informative procedure for the diagnosis, which can differentiate Rotor syndrome from Dubin-Johnson syndrome. A 26-year-old man was admitted due to asymptomatic persistent jaundice. Physical examination revealed icteric sclera without hepatosplenomegaly. Laboratory findings showed increased serum bilirubin with direct bilirubinemia. Markedly decreased hepatic uptake and poor visualization of the gallbladder and biliary tract were shown in ^(99m)Tc-DISIDA scan. Histology of the liver showed no diagnostic abnormality without pigmentation. But, we report a case of Rotor syndrome that showed characteristic cholescintigraphic findings with normal urinary total coproporphyrin excretion.

HCV, Alcoholic : PO-14 ; The significance of megaloblastic change during treatment of hepatitis C patients

( Haak Cheoul Kim ),( Eun Young Cho ),( Young Bum Cho ),( Ji Won Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background and Aims: For Hepatitis C virus (HCV) infection, pegylated interferon and ribavirin treatment are used as standard treatments, but they can make various hematologic adverse events. If such an adverse event arises, does should be reduced dosage, which may drop the treatment response. Also it is often reported that anemia occurrence can be an indicator of the good treatment response. We confirmed that Mean corpuscular volume (MCV) increase was not unusual during the HCV standard treatment and tried to find out the meaning of MCV increase during the process of HCV treatment. Methods: The subjects of the study were 60 outpatients who visited Wonkwang University Hospital because of chronic C viral hepatitis and were treated with pegylated interferon and ribavirinfrom from 2005 to 2010 and whose SVR could be identified. The medical records of the subjects were analyzed. CBC, blood chemistry, HCV RNA (copies/mL), T4 free and TSH were reviewed at 0, 4, 12, 24, 48 and 72 week after the treatment, and aspartate aminotransferase to platelet ratio index(APRI) was calculated based on the blood test result. Additionally, abdomen ultrasound scan was performed to check if there is a cirrhotic change. Results: 1. The subjects were 31 males and 29 females by gender, and 19 Genotype 1, 40 Genotype 2 and 1 Genotype 3 by Genotype. 24 patients were treated with interferon α2a, and 36 with pegylated interferon α2b. Regarding ribavirin dose, 11 patients had less than 800mg, 37 patients had 800mg ~ <1000mg, and 12 patients had ≥1000mg. Ten patients showed significant drinking history (80 g/day). 2. When classifying the group with the baseline of MCV 95fL before the treatment (Group 1, MCV< 95 fL; Group 2, MCV ≥95 fL) 16 subjects showed over 95 fL MCV, and there was no significantly different factors between groups (all≥0.05). The only significantly different factor was average age such as 59.1±13.5 in Group 1 and 64.0±7.19 in Group 2, which showed borderline significance (p=0.076). 3. Regarding the increase of MCV during the treatment, it increased regardless of Genotype at 4, 12, and 24 weeks and decreased from 48 weeks. (Genotype 1: 90.92±3.62, 90.95±4.03, 94.52±6.74, 97.43±7.31, 93.68±5.36, 91.36±5.56 in week 0, week 4, week 12 (p=0.000), week 24 (p=0.024), week 48, week 72, retrospectively; Genotype 2: 92.26±5.87, 93.54±5.66, 97.13±6.55, 98.08±7.11, 92.72±4.82, 92.58±4.99 in week 0, week 4 (p=0.000), week 12 (p=0.000), week 24 (p=0.000), week 48, week 72, retrospectively) 4. There was statistically significant difference in Hemoglobin (week 0, 2, 4, 12, 24) and platelet count (week 0, 2, 12, 24, 48, 72) and albumin (week 0, 4, 12, 24, 48, 72) (all p≤0.05) when dividing group with the standard of MCV ≥100fL (Group 3, MCV< 100 fL; Group 4, MCV ≥100 fL), which showed significant correlation when it was divided by APRI >0.08. Group 4 had more patients who showed cirrhotic changes on the sonography comparing to Group 3 (3/29(21.4%) in Group 3, 11/31(78.6%) in Group 4, p=0.021). Conclusions: Although MCV increase during the treatment was not related with the treatment response, it seemed to be related with chronicity of hepatitis. Thus, such patients should be closely observed even after the termination of the treatment.

HCV, Alcoholic : PO-14 ; The significance of megaloblastic change during treatment of hepatitis C patients

( Haak Cheoul Kim ),( Eun Young Cho ),( Young Bum Cho ),( Ji Won Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background and Aims: For Hepatitis C virus (HCV) infection, pegylated interferon and ribavirin treatment are used as standard treatments, but they can make various hematologic adverse events. If such an adverse event arises, does should be reduced dosage, which may drop the treatment response. Also it is often reported that anemia occurrence can be an indicator of the good treatment response. We confirmed that Mean corpuscular volume (MCV) increase was not unusual during the HCV standard treatment and tried to find out the meaning of MCV increase during the process of HCV treatment. Methods: The subjects of the study were 60 outpatients who visited Wonkwang University Hospital because of chronic C viral hepatitis and were treated with pegylated interferon and ribavirinfrom from 2005 to 2010 and whose SVR could be identified. The medical records of the subjects were analyzed. CBC, blood chemistry, HCV RNA (copies/mL), T4 free and TSH were reviewed at 0, 4, 12, 24, 48 and 72 week after the treatment, and aspartate aminotransferase to platelet ratio index(APRI) was calculated based on the blood test result. Additionally, abdomen ultrasound scan was performed to check if there is a cirrhotic change. Results: 1. The subjects were 31 males and 29 females by gender, and 19 Genotype 1, 40 Genotype 2 and 1 Genotype 3 by Genotype. 24 patients were treated with interferon α2a, and 36 with pegylated interferon α2b. Regarding ribavirin dose, 11 patients had less than 800mg, 37 patients had 800mg ∼ <1000mg, and 12 patients had ≥1000mg. Ten patients showed significant drinking history (80 g/day). 2. When classifying the group with the baseline of MCV 95fL before the treatment (Group 1, MCV< 95 fL; Group 2, MCV ≥95 fL) 16 subjects showed over 95 fL MCV, and there was no significantly different factors between groups (all≥0.05). The only significantly different factor was average age such as 59.1±13.5 in Group 1 and 64.0±7.19 in Group 2, which showed borderline significance (p=0.076). 3. Regarding the increase of MCV during the treatment, it increased regardless of Genotype at 4, 12, and 24 weeks and decreased from 48 weeks. (Genotype 1: 90.92±3.62, 90.95±4.03, 94.52±6.74, 97.43±7.31, 93.68±5.36, 91.36±5.56 in week 0, week 4, week 12 (p=0.000), week 24 (p=0.024), week 48, week 72, retrospectively; Genotype 2: 92.26±5.87, 93.54±5.66, 97.13±6.55, 98.08±7.11, 92.72±4.82, 92.58±4.99 in week 0, week 4 (p=0.000), week 12 (p=0.000), week 24 (p=0.000), week 48, week 72, retrospectively) 4. There was statistically significant difference in Hemoglobin (week 0, 2, 4, 12, 24) and platelet count (week 0, 2, 12, 24, 48, 72) and albumin (week 0, 4, 12, 24, 48, 72) (all p≤0.05) when dividing group with the standard of MCV ≥100fL (Group 3, MCV< 100 fL; Group 4, MCV ≥100 fL), which showed significant correlation when it was divided by APRI >0.08. Group 4 had more patients who showed cirrhotic changes on the sonography comparing to Group 3 (3/29(21.4%) in Group 3, 11/31(78.6%) in Group 4, p=0.021). Conclusions: Although MCV increase during the treatment was not related with the treatment response, it seemed to be related with chronicity of hepatitis. Thus, such patients should be closely observed even after the termination of the treatment.

The Role of Economic Cluster Perspectives in Regional Economic Development

Haak, Robert,Vora, Gautam,Walsh, Steven T.,White, Craig G. World Technopolis Association 2014 World Technopolis Review Vol.3 No.1

The importance of science and technology as the root of exceptional regional economic development has been extolled since the time of Schumpeter. Today emerging technologies are signaling the start of a new economic cycle where regions that are effective in technology translation will gain advantage. The will of policymakers to translate technology into regional job and wealth creation seems to be at an all-time high. Yet an improved process for translating technical development into regional prosperity has proved elusive. If there are no processes other than applying techniques that have worked in the past for other regions to a new region then there is cause for concern. Here the authors seek to add to this field of knowledge by applying elements of the varied cluster theories to provide a basis for policy for regional economic development by turning science and technology into commercial innovation. We provide a review of current cluster theories and discuss the positive and negative issues associated with each. We propose a model that allows interested professionals to utilize aspects of each cluster perspective geared to the realities of their specific area.

Macroaspartasemia as a Cause of Isolated Elevation of Aspartate Aminotransferase - Its Biochemical and Physiological Characteristics -

( Haak Cheoul Kim ),( Je Hyung Kim ) 대한내과학회 1997 The Korean Journal of Internal Medicine Vol.12 No.2

Effects of Endoscopic Variceal Ligation in Lower Esophageal Motor Function: A Prospective Study

( Haak Cheoul Kim ),( Ju Hung Song ),( Hyeong Eon Kim ),( Suck Chei Choi ),( June Hyung Lyou ),( Tae Hyeon Kim ),( Bong Joo Shin ) 대한내과학회 1995 The Korean Journal of Internal Medicine Vol.10 No.2

한국인 만성 B형 간염 바이러스 ( HBV ) 보유자에서 HBV 유전자형 - 일차 중합 효소 반응법에 의한 온전한 B 형 간염 바이러스 증폭 및 그의 염기 서열 -

김학철(Haak Cheoul Kim),서검석(Geom Suk Seo),김용성(Youg Sung Kim),송우건(Woo Gun Song),문형배(Hyung Bae Moon),조지현(Jie Heun Cho) 대한내과학회 2001 대한내과학회지 Vol.61 No.5

N/A Background : Hepatitis B virus (HBV) is major source of chronic liver disease in Korea. However this virus might have different nucleotide sequence according to races, different region, etc. Recently the novel method that allows sensitive amplification with dramatically decreased mis-incorporation has developed. We determined to get the major form of HBV nucleotide sequence from whole sequencing data of 26 Korean HBV carriers. Methods : HBV DNA were collected from 26 Korean chronic HBV carriers. We used the novel PCR with pfu for the amplification of HBV DNA, and specific primers were made with combination sequence bases of non-HBV part and HBV parts which were located head and tail in the virion. Then whole length of HBV were directly sequenced and analysed. Result : HBV DNA was consisted of 3215 bases in 20 cases of 26 Korean chronic HBV carriers. And the remainder had smaller or larger number due to deletion, insertion or both in pre-S2 and S gene. They were 99.03% homology of their nucleotide sequence and belong to genotype C. The variability of nucleotide sequence was significantly higher in the singly coding region (SCR) than doubly coding region (DCR), and also high in pre-S1 and pre-S2 gene among the DCR. Hot-spots were more frequently found in the SCR, pre-S1 and pre-S2 gene. Conclusion : In Korean chronic HBV carriers, HBV is consisted of 3215 nucleotides, and belongs to genotype C. And it might exist one genotype with the variability in Korea.(Korean J Med 61:479-488, 2001)

Chronic intermittent hypoxia exacerbates lung fibrosis in bleomycin-induced lung injury mouse model

( Sang Haak Lee ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.0

Introduction: Obstructive sleep apnea (OSA) is highly common among patients with idiopathic pulmonary fibrosis. OSA causes chronic intermittent hypoxia (CIH) during sleep. We aimed to investigate the effect of CIH on bleomycin (BLE)-induced pulmonary fibrosis in mice and to explore putative mechanisms. Methods: C57/BL6 mice were divided into four groups and then exposed to normoxia (NOR) condition or CIH for 2 weeks prior to the intratracheal injection of BLE. After BLE instillation, mice were exposed to CIH or NOR for 4 weeks. Fibrosis was evaluated by masson trichrome stain, Sirius red and hydroxyproline assay. The mRNA expressions or protein levels of fibrosis-related genes were measured by real-time PCR and western blot in lung tissue, respectively. Results: Lung histology and special staining results showed that CIH led to scattered fibrotic changes in alveolar structure and substantive fibrotic tissue dominantly situated in the perivascular space. In BLE treated group, CIH compared to NOR increased hydroxyproline (p<0.001) in lung tissue and TGF-β (p<0.01) in serum. CIH increased the mRNA and protein levels of TGF-β, and collagen type 1 in BLE group, though the difference was not statistically significant. The protein levels of TGF-β and collagen type 1 were elevated in CIH with BLE treated group. The protein level of epithelial to mesenchymal transition regulator, snail, and phosphorylation of extracellular signal-regulated kinase (ERK)1/2 were notably increased in CIH with BLE treated group. Conclusion: The findings demonstrate that CIH might exacerbate the progression of BLE induced pulmonary fibrosis via TGF-β/ERK/snail signaling and provide proof of concept of targeting this pathway in fibrotic lung disease.