생체적합성과 생분해성을 갖는 Polypeptide Copolymers의 합성과 물성에 관한 연구(Ⅲ): Polypeptide Hydrogels의 약물조절방출

강인규,권대룡,성용길 동국대학교 자연과학연구소 1991 자연과학연구 논문집 Vol.11 No.-

Poly(γ-benzyl L-glutamate) (PBLG)의 측쇄에 polyethylene glycol(PEG) 또는 ethanolamie(EA)을 반응시켜 적심성이 서로 다른 몇가지 폴리펩티드 공중합체를 합성하였고, 이들 공중함체의 약물방출특성을 살펴보았다. 합성된 폴리펩티드공중합체의 수분흡수율은 공중합체 중의 PEG 또는 EA 함량이 높아짐에 따라 증가하였다. PEG-PBLG-EA 공중합체로부터의 5-fluorouracil의 방출속도는 PEG-PBLG 공중합체로부터의 방출속도보다 크게 나타났으며, 이러한 결과는 팽윤성의 폴리펩티드를 합성하고자 할 때 사용되는 치환제로서는 PEG보다도 EA가 더욱 효과적이라는 것이 나타났다. 한편, PEG를 가교시킨 PBLG 공중합체막상에서는 5-fluorouracil의 방출에 기인하여 작은 pores를 명료하게 나타나고 있음을 알 수 있었다. Several copolypeptides having different swellabilities are are synthesized by introducing polyethylene glycol(PEG) or ethanolamine(EA) to the side chains of poly(γ-benzyl L-glutamate) (PBLG) and their drug release characteristics are examined. The degree of swelling of copolypeptide is increased by increasing PEG or EA content in the polymer. The release rate of 5-fluorouracil from the PEG-PBLG-EA copolymers was higher than that of the PEG-PBLG copolymers. This results indicated that EA is more effective than PEG for the preparation of the swellable polypeptides. It was observed, from the morphological study by scanning electron microscope, the pores are generated on the PEG-crosslinked PBLG, but not on the PEG-grafted-PBLG.

방선균 분리주가 생산하는 Phospholipase C 저해물질인 MT2617-2B의 분리 및 특성

고학룡,이현선,오원근,안순철,김보연,강대욱,민태익,안종석 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.1

방선균 분리주 MT2617-2의 배양액으로 부터 phospholipase C (PLC) 저해물질인 MT2617-2B를 n-butanol 추출 및 column chromatography 법을 이용하여 분리하였다. MT2617-2B는 IR ^13C- 및 ^1H-NMR 그리고 ESI-MS에 의한 구조분석 결과, 한 개의 hemiketal ring, polyhydroxyl 및polymethyl groups으로 구성되었으며 side chain으로 한 개씩의 malonate 및 guanidine group을 가지는 분자량 1057의 macrolide 화합물이었다. 따라서, MT2617-2B를 기존의 macrolide 항생제인 copiamycin 및 niphithricin A로 동정하였다. 한편, MT2617-2B는 methanol 용액에서 실온에서 방치하였을 때 도일한 분자량을 가진 두 개의 이성질체를 생성하였다. PLC γ1과 -β1에 대해 각각 25 및 50㎍/㎖의 IC_50 값을 가지며, Staphylococcus aureus 와 Candida albicans에 대해서는 항균활성을 나타내지만 Escherichia coli에는 나타내지 않았다. A phospholipase C (PLC) inhibitor (MT2617-2B) was isolated from the culture broth of actionmycetes isolate MT2617-2 by the extraction with n-butanol and column chromatographic techniques. The molecular weight of the inhibitor was 1057, by the spectroscopic analyses of IR ^13C- and ^1H-NMR and ESI-MS. The chemical structure of MT2617-2B was found to be a macrolide compound consisted of a hemiketal ring, polyhydroxyl and polymethyl groups, which had a malonate and guanidine group as its side chain. MT2617-2B produced its two isomers having the same molecular weight by standing in methanol solution at room temperature. Therefore, MT2617-2B was identified as copiamycin and niphithricin A, macrolide antibiotics. The values of IC_50 against PLC γ1 and PLC-β1 were 25 and 50㎍/㎖, respectively. MT2617-2B had antimicrobial activities against Staphylococcus aureus and Candida albicans, but not against Escherichia coli.

말초혈액에서 Tg mRNA에 대한 역전사 중합효소 연쇄 반응법의 갑상선 재발암의 분자생물학적 진단

권성일,박기룡,김현영,신채희,임영찬,최영식,박요한,이강대,장희경,이재화,염하용 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.4

연구배경: 갑상선암은 다른 조직에 발생한 암에 비해 비교적 천천히 자라므로 대부분 예후가 양호하지만, 일부에서는 주위 조직으로 침윤하거나 혹은 원격 전이로 인하여 치명적인 결과를 초래할 수 있다. 갑상선전절제술 및 131^I 제거술 후 경과 관찰시 갑상선암의 재발과 전이의 진단에 있어 131^I 스캔과 혈청 Tg의 측정이 현재 임상에서 가장 많이 이용되고 있으나 이 방법에는 여러 가지의 결점이 있다. 최근 Tg mRNA에 대한 RT-PCR법을 이용한 여러 연구결과는 131^I 스캔과 혈청 Tg 측정의 결점을 보완할 수 있는 좋은 보조적인 진단법으로 이용할 수 있을 가능성을 제시하였다. 이에 말초혈액에서 측정한 Tg mRNA에 대한 RT-PCR법이 갑상선 절제술 및 방사성요드 치료 후 갑상선암의 재발 및 전이 유무의 진단에 유용한가를 알아보고자 이 연구 시행하였다. 방법: 분화된 갑상선암으로 진단된 후 갑상선전절제술을 시행받고 방사성요드 치료를 받은 환자 중 현재까지 한차례에 이상 추적 방사성요드 전신 스캔을 시행하고 추적관찰이 가능했던 유두선암 35예, 여포선암 5예를 대상으로 연구를 시행하였다. 대상군은 131^I 스캔 소견상 음성인 군(Group Ⅰ), 잔여조직이 있는 군(Group Ⅱ), 국소전이가 있는 군(Group Ⅲ), 및 원격전이 군(Group Ⅳ)으로 구분하였다. 정상 대조군은 갑상선질환이 없는 10예의 건강인으로 하였다. 대상환자의 말초혈액을 이용한 Tg mRNA에 대해 특이적인 primer를 이용하여 RT-PCR 및 nested RT-PCR을 시행하였다. 결과: 본 연구 결과는 다음과 같다. 1) 131^I 스캔 소견상 음성인 군 21예 중 1예에서 Tg가 양성소견을 보였다. Anti Tg Ab가 양성인 4예 모두 Tg가 음성을 보였다. 잔여조직이 있거나 국소전이 및 원격전이를 보인 군 19예 중 Tg가 양성인 경우는 4예였으나, Tg mRNA는 전예에서 양성이었다. 2) 131^I 스캔에서 국소 및 원격전이 소견을 보인 8예 중 4예에서 Tg가 음성으로 131^I 스캔과 혈청 Tg 사이에 불일치 소견을 보였다. 3) 말초혈액에서 특이적인 primer를 이용하여 RT-PCR 및 nested RT-PCR을 시행한 결과 대상군 40예 및 정상 대조군 10예 모두에서 Tg mRNA가 양성을 보였다. 결론: 본 연구에서 갑상선 절제술 및 방사성요드 치료 후 갑상선암의 재발 및 전이 유무를 평가함에 있어 역전사 중합효소 연쇄 반응법을 이용한 Tg mRNA 측정의 의의는 재평가되어야 한다고 생각된다. Background: Differentiated thyroid cancer is the most common endocrine malignancy. Despite advances in the treatment of thyroid cancer, disease recurrence and metastasis may occur in as many as 20% of patients, and so continues to pose major problems in its clinical management. Serum thyroglobulin (Tg) measurements, by immunoassay, are used to detect residual or recurrent thyroid cancer following thyriod ablation. However, the usefulness of immunoassay is limited by both the requirement for thyroid hormone withdrawal, to attain optimal test sensitivity, and interference by the antithyroglobulin antibody (Anti-Tg Ab). Recent studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of Tg mRNA in the peripheral blood of patients with differentiated thyroid carcinomas. We performed this study to evaluated the usefulness RT-PCR of Tg mRNA in peripheral blood of patients with thyroid carcinoma following a total thyroidectomy and radioiodine ablation therapy. Methods: Forty cases that underwent a total thyroidectomy and radioiodine ablation therapy were included in this study. Of the 40 patients, 35 were papillary carcinomas and 5 were follicular carcinomas. Ten normal control subjects were also studied. Tg mRNA was extracted. Then RT-PCR and nested RT-PCR, were run with specific Tg primers. Concurrently, DNA sequencing of the isolates was carried out to prove the isolates were identical to the nucleotide sequence of the Tg. Results: The Tg was detected in 4 of 19 patients, with either a residual thyroid bed, or metastasis, on a 131^I whole body scan and in 1 of 21 patients with a negative radioiodine scan. Surprisingly, the Tg mRNA was detected in all the patients and normal controls. Conclusion: From our results we can not recommend Tg mRNA, detected by RT-PCR in peripheral blood, as a tumor marker superior to that of the Tg serum level. We consider an intensive re-evaluation of the method is required before considering its clinical applications (J Kor Soc Endocrinol 17:501∼513, 2002).

Trends in research on indoor radon exposure and lung cancer in South Korea

Kang, Dae Ryong,Kang, Dongmug,Min, Kyoung-Bok,Kim, Changsoo,Oh, Sung-Soo,Koh, Sang-Baek BioMed Central 2016 Annals of occupational and environmental medicine Vol.28 No.1

Elevated On-Treatment Diastolic Blood Pressure and Cardiovascular Outcomes in the Presence of Achieved Systolic Blood Pressure Targets

Dae-Hee Kim,In-Jeong Cho,Woohyeun Kim,Chan Joo Lee,Hyeon-Chang Kim,Jeong-Hun Shin,Si-Hyuck Kang,Mi-Hyang Jung,Chang Hee Kwon,Ju-Hee Lee,Hack Lyoung Kim,Hyue Mee Kim,Iksung Cho,Dae Ryong Kang,Hae-Young 대한심장학회 2022 Korean Circulation Journal Vol.52 No.6

Background and Objectives: This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). Methods: A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). Results: During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated on-treatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10; 95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. Conclusion: Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.

Epidemiological studies on indoor radon exposure in Korea

Dae Ryong Kang(강대용) 환경독성보건학회 2019 한국독성학회 심포지움 및 학술발표회 Vol.2019 No.4

Trends in research on indoor radon exposure and lung cancer in South Korea

Dae Ryong Kang(강대용) 환경독성보건학회 2016 한국독성학회 심포지움 및 학술발표회 Vol.2016 No.6

Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes.

Kang, Young Sun,Park, Yun Gyu,Kim, Bo Kyung,Han, Sang Youb,Jee, Yi Hwa,Han, Kum Hyun,Lee, Mi Hwa,Song, Hye Kyoung,Cha, Dae Ryong,Kang, Shin Wook,Han, Dae Suk Journal of Endocrinology (Ltd. by Guarantee) 2006 Journal of molecular endocrinology Vol.36 No.2

<P>Angiotensin II (Ang-II) and vascular endothelial growth factor (VEGF) have an important role in the pathogenesis of diabetic nephropathy, but the signaling cascade of VEGF regulation in response to Ang-II in podocytes is largely unknown. In these experiments, we looked at the effect of Ang-II on the production of VEGF, and investigated whether VEGF production depends on the p38 mitogen activated protein kinase (MAPK) pathway in cultured mouse podocytes. Incubation of podocytes with Ang-II induced a rapid increase in VEGF mRNA expression and protein synthesis as well as its transcriptional activity in an Ang-II dose-dependent manner. To further define the role of angiotensin type 1 (AT1) and type 2 (AT2) receptors involved in Ang-II-mediated VEGF synthesis, the effects of selective AT1 and AT2 receptor antagonists were evaluated. Prior treatment with losartan significantly inhibited VEGF mRNA and protein synthesis induced by Ang-II, which suggests that the AT1 receptor is involved in Ang-II-mediated VEGF synthesis. Furthermore, stimulation of the cells with Ang-II increased both phosphorylation of p38 MAPK and MAP kinase kinase 3/6 (MKK3/6). Additionally, Ang-II enhanced the DNA binding activity to cAMP response element binding protein (CREB) and phosphorylation of CREB. In addition, to investigate the role of p38 MAPK in Ang-II-induced VEGF synthesis, podocytes were pretreated with or without the p38 MAPK inhibitor, SB203580 for 24 h to observe whether Ang-II-mediated VEGF synthesis was inhibited by blocking p38 MAPK. The addition of SB203580 led to a marked inhibition of the increased VEGF mRNA and protein production induced by Ang-II in a dose-dependent manner. Taken together, these results suggest that Ang-II stimulates the synthesis of VEGF in podocytes and the production of VEGF induced by Ang-II is mediated, in part, through the activation of the p38 MAPK pathway.</P>

Trends in research on indoor radon exposure and lung cancer in South Korea

Dae Ryong Kang,Dongmug Kang,Kyoung-Bok Min,Changsoo Kim,Sung-Soo Oh,Sang-Baek Koh 대한직업환경의학회 2016 대한직업환경의학회지 Vol.28 No.-

Statistical Methods for Causal Inference in Environmental Epidemiologic Studies

Dae Ryong Kang(강대용) 환경독성보건학회 2017 한국독성학회 심포지움 및 학술발표회 Vol.2017 No.2