서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1

<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>

Organic Solar Cells: Solution‐Processable Reduced Graphene Oxide as a Novel Alternative to PEDOT:PSS Hole Transport Layers for Highly Efficient and Stable Polymer Solar Cells (Adv. Mater. 42/2011)

Yun, Jin‐,Mun,Yeo, Jun‐,Seok,Kim, Juhwan,Jeong, Hyung‐,Gu,Kim, Dong‐,Yu,Noh, Yong‐,Jin,Kim, Seok‐,Soon,Ku, Bon‐,Cheol,Na, Seok‐,In WILEY‐VCH Verlag 2011 Advanced Materials Vol.23 No.42

<P>Solution‐processable reduced graphene oxide as a hole‐transporting layer for highly efficient and stable organic solar cells is reported on page 4923 by Dong‐Yu Kim, Seok‐In Na, and co‐workers. Introduction of a newly reduced graphene oxide by simple solution processing into solar cells dramatically raises the cell efficiency and cell life‐time. The results will allow full use of chemically reduced graphene and will advance the realization of carbon‐based printable optoelectronic devices. </P>

Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury

Kim, Kyeong Seok,Yang, Hun Yong,Song, Hosup,Kang, Ye Rim,Kwon, JiHoon,An, JiHye,Son, Ji Yeon,Kwack, Seung Jun,Kim, Young-Mi,Bae, Ok-Nam,Ahn, Mee-Young,Lee, Jaewon,Yoon, Sungpil,Lee, Byung μ,Kim, Hyung TAYLOR & FRANCIS 2017 Journal of Toxicology and Environmental Health Vol.80 No.9

<P>Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.</P>

Curcumin ameliorates cadmium-induced nephrotoxicity in Sprague-Dawley rats

Kim, Kyeong Seok,Lim, Hyun-Jung,Lim, Jong Seung,Son, Ji Yeon,Lee, Jaewon,Lee, Byung Mu,Chang, Seung-Cheol,Kim, Hyung Sik Elsevier 2018 Food and chemical toxicology Vol.114 No.-

<P><B>Abstract</B></P> <P>Chronic exposure to cadmium (Cd) causes remarkable damage to the kidneys, a target organ of accumulated Cd after oral administration. The aim of the present study was to investigate the protective effect of curcumin against Cd-induced nephrotoxicity. Sprague–Dawley male rats were divided into the following four treatment groups: control, curcumin (50 mg/kg, oral), CdCl<SUB>2</SUB>, (25 mg/kg, oral), and pre-treatment with curcumin (50 mg/kg) 1 h prior to the administration of CdCl<SUB>2</SUB> (25 mg/kg, oral) for 7 days. At 24 h after the final treatment, the animals were killed, and the biomarkers associated with nephrotoxicity were measured. Our data indicated that blood urea nitrogen (BUN) and serum creatinine (sCr) levels were significantly reduced by curcumin pre-treatment in CdCl<SUB>2</SUB>-treated animals. Histopathological studies showed hydropic swelling and hypertrophy of the proximal tubular cells in the renal cortex after Cd treatment. Pretreatment with curcumin ameliorated the histological alterations induced by Cd. The urinary excretion of kidney injury molecule-1 (Kim-1), osteopontin (OPN), tissue inhibitor of metalloproteinases 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL), and netrin-1 significantly reduced by curcumin treatment compared to that in the CdCl<SUB>2</SUB>-treated group. The administration of curcumin provided a significant protective effect against Cd-induced nephrotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Curcumin protects against cadmium-induced renal injury. </LI> <LI> Curcumin reduces urinary excretion of AKI biomarkers. </LI> <LI> Curcumin protects against cadmium-induced apoptosis in the kidney. </LI> </UL> </P>

한국인 갑상선 수질암 환자에서 RET 원종양유전자 점돌연변이 양상

김형훈,김현진,정윤재,민용기,이명식,이문규,김광원,기창석,김종원,정재훈 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경: 갑상선 수질암의 25∼30%는 유전성으로 발현되는데, MEN 2A, MEN 2B 또는 가족성 수질암의 형태로 나타난다. RET 원종양유전자의 점돌연변이가 유전성 갑상선 수질암의 발생에 중요한 역할을 하므로, 진단 당시의 연령이나 가족력 유무에 관계없이 모든 갑상선 수질암 환자나 또는 RET 변이가 발견된 수질암 환자의 가족 구성원들에서 RET 변이 검색을 하여야 한다. 또한 일부 문헌에서 RET 변이의 양상에따라 임상상이 다르게 표현됨이 보고된 바 있다. 이에 저자들은 한국인 갑상선 수질암 환자에서 RET 원종양유전자의 점돌연변이의 양성률을 알아보고, 변이 양상에 따른 임상상의 차이가 있는지를 알아보고자 본 연구를 시행하였다. 방법: 치근 7년간 본원에서 갑상선절제술을 통해 갑상선 수질암으로 진단받은 29예에서 RET 원종양유전자의 점돌연변이 검사를 시행하였다. 29예의 평균연령은 39세(20∼60세)이었고, 남자 7예, 여자 22예 이었다. 이들의 말초혈액에서 genomic DNA를 분리하고, 특이 시발차를 이용하여 RET 원종양유전자의 exon10, 11, 13, 14, 16부위를 증폭하였다. 증폭된 부위를 자동염기서열분석기를 이용하여 직접 분석하였다. 양성으로 나온 경우는 모든 가족 구성원을 대상으로 RET 변이 유무를 검색하였다. 결과: 대상 환자 29예 중 9예 (31%)에서 RET 원종양유전자 점돌연변이가 발견되었다 RET 변이가 발견된 9예 (남자 3예, 여자 6예)의 평균 연령은 33세 (20∼51세)로 RET 변이가 발견되지 않은 20예의 평균연령 42세(24∼60세)보다 의미 있게 적었다. RET 변이가 발견된 9예 중 MEN 2A가 5예, 가족성 수질암이 1예, 그리고 산발성 수질암이 3예이었고, MEN 2B는단 1예도 진단되지 않았다. MEN 2A 5예 중 4예는 exon 11의 codon 634번(C634R 2예, C634Y 2예)에서, 그리고 나머지 1예는exon 10의 codon 618번 (C618R)에서 변이가 각각 발견되었다. 가족성 수질암 1아는 codon 634번(C634W)에서, 산발성 수질암 3예도 모두 codon 634번 (C634y 2예, C634s 1예)에서 각각 변이가 발견되었다. RET변이 양상 또는 위치에 따른 임상상의 차이는 발견할 수 없었다. 결론: 갑상선 수질암 환자 31%에서 RET 원종양유전자의 점돌연변이를 발견할 수 있었다. 유전성 수질암 중 가족성 수질암 1예를 제외하고 나머지 5예는MEN 2A이었다. 저자들의 5예와 지금까지 국내에서 보고 된 7예를 합친 국내 MEN 2A 12예 중 75% (9/12)는 exon 11의codon 634번(C634R 4예, C634y 4예, C634w 1예)에서, 그리고 나머지 25% (3/12)는 exon 10의 codon618번(C618R 2예, C618s 1예)에서 변이가 발견되었다. 국내에서는 codon 634과 codon 618 두 곳에만 국한된 양상이었고, codon 634에서의 C634R 변이는 1/3에서만 나타났다. 비록 본 연구에서는 제한된 환자 수 때문에 변이 양상과 임상상의 관계를 규명할 수 없었지만, 향후 많은 수의 환자를 대상으로 전향적인 연구를 시행하여 genotype-phenotype 관계 규명을 하는 것이 필요하다. Background: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 -30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. Methods: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. Results: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. Conclusion: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this (J Kor SOC Endocrinol 18:360-370, 2003).

Assessment of In Vitro Assay System for Thyroid HormoneDisruptors Using Rat Pituitary GH3 Cells

Hee Jin Kim1,Hae Young Park1,Jeonga Kim1,Il Hyun Kang2,Tae Sung Kim2,Soon Young Han2,Tae Seok Kang2,Kui Lea Park2,Hyung Sik Kim1 한국독성학회 2006 Toxicological Research Vol.22 No.4

The development of in vitro assays has been recommended to screening and test-ing the potential endocrine disruptors (EDs). These assay systems focus only on identifying thethe thyroid hormone (TH) disruptors. The aim of this study was to evaluate a test system to detectTH disruptors using rat pituitary tumor GH3 cells. The test system is based on the TH-dependentincrease in growth rate. As expected, L-3,5,3-triiodothyronine (T3) markedly induced a morphologicalchange in GH 3 cells from flattened fibroblastic types to rounded or spindle-shaped types. T3 stimu-lated GH3 cell growth in a dose-dependent manner with the maximum growth-stimulating effect9 M. In addition, T3 increased the release of growth hor-mone and prolactin into the medium of the GH3 cells culture. Using this assay system, the TH-dis-rupting activities of bisphenol A (BPA) and its related compounds were examined. BPA,dimethylbisphenol A (DMBPA), and TCI-EP significantly enhanced the growth of GH3 cells in therange of 1 × 10-5M to 1 × 10-6M concentrations. In conclusion, this in vitro assay system might bestandardization before it can be used as a broad-based screening tool.

T1b 병기의 신세포암에서 수술 후 예후를 예측할 수 있는 임상 및 병리학적 인자에 대한 연구

오승용, 김영원, 윤형윤, 서성필, 이상근, 김원태, 윤석중, 이상철, 김원재, 김용준 충북대학교 의과대학 충북대학교 의학연구소 2014 忠北醫大學術誌 Vol.24 No.1

연구목적: T1병기의 국소신세포암(localized clear-cell renal cell carcinoma)은 근치적신적출술이 나 부분신절제술이 표준치료이며 수술 후 타 병기에 비해 양호한 예후를 보인다. 하지만, 많은 수의 환 자에서 추적관찰 중 재발 및 사망이 발생하는데, 이는 T1b 병기에서 더 높게 보고되고 있다. 본 연구 에서는 국소신세포암 중 T1b 병기의 신세포암에서 표준적 치료 후 환자의 예후에 영향을 주는 임상 및 병리학적 인자에 대하여 알아보고자 하였다. 대상 및 방법: 1999년부터 2011년 까지 5개 기관에서 근치적신적출술이나 부분신제술을 시행 받은 3567명의 국소신세포암 환자들 중 병리학적 병기가 T1b로 확진 된 702명을 대상으로 하였다. 이들 환자가 가지는 임상 및 병리학적 특성 [연령, 성별, 고혈압, 당뇨, 비만도, European Cooperative Oncology Group(ECOG) 수행도, 증상유무, 수술방법, 종양크기, 분화도, 조직학적 형태 등]을 이용 하여 환자의 예후 [무재발생존율(relapse-free survival), 암특이생존율(cancer-specific survival) 및 전체생존율(overall survival)]에 영향을 미치는 인자에 대하여 다양한 방법으로 비교분석 하였다. 결과: 추적 관찰 기간은 34.0개월 (중앙값, 0-152개월)이었으며, 이 기간 중 재발, 사망 및 암특이사 망은 각각 72례 (10.3%), 57례 (8.1%) 및 24례 (3.4%)에서 발생하였다. 단변량 및 다변량 Cox 비례위험회귀분석에서 다양한 인자들이 무재발생존율(당뇨 유무, 종양크기 및 Fuhrman등급), 암특이 생존율(나이, 체질량지수, 당뇨 유무, 종양크기) 및 전체생존율(나이, 체질량지수, ECOG 수행도, 종 양크기)에 영향을 줄 수 있는 독립적 예후인자였다. 결론: 본 연구결과 국소신세포암의 예후를 예측할 수 있는 다양한 임상 및 병리학적 인자를 확인 할 수 있었다. 이러한 위험인자를 가지고 있는 환자는 보다 적극적인 추적관찰을 통하여 재발을 조기에 발 견한다면 이들의 생존율 향상에 많은 기여를 할 수 있을 것으로 생각한다.

Original Article : Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

( Ji Yeon Son ),( Yoon Jong Kang ),( Kyeong Seok Kim ),( Tae Hyung Kim ),( Sung Kwang Lim ),( Hyun Jung Lim ),( Tae Cheon Jeong ),( Dal Woong Choi ),( Kyu Hyuck Chung ),( Byung Mu Lee ),( Hyung Sik Ki 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

Son, Ji Yeon,Kang, Yoon Jong,Kim, Kyeong Seok,Kim, Tae Hyung,Lim, Sung Kwang,Lim, Hyun Jung,Jeong, Tae Cheon,Choi, Dal Woong,Chung, Kyu Hyuck,Lee, Byung Mu,Kim, Hyung Sik Korean Society of ToxicologyKorea Environmental Mu 2014 Toxicological Research Vol.30 No.2

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.