Prostaglandin A₂-induced Apoptosis is Not Inhibited by Heme Oygenase-1 in U2OS Cells

Kyoung-Won Ko(고경원),Sun-Young Lee(이선영),Ji-Hyun Ahn(안지현),Jaetaek Kim(김재택),In-Kyung Kim(김인경),Ho-Shik Kim(김호식) 한국생명과학회 2008 생명과학회지 Vol.18 No.11

Prostaglandin A₂ (PGA₂)는 사람 골육종 세포인 U2OS 세포주에서 apoptosis와 heme oxygenase (HO)-1의 발현을 함께 유도하였다. PGA₂에 의한 apoptosis는 HO-1의 과도한 발현이나 HO-1에 대한 small interfering RNA에 의한 발현저하에 의하여 변동되지 않았으나 H₂O₂에 의한 세포사망은 HO-1의 발현 수준에 반비례하여 변동되었다. 또한 thiol antioxidant인 N-acetyl-L-cysteine (NAC)은 PGA₂에 의한 세포사망과 HO-1의 발현 증가를 모두 차단하였지만, non-thiol antioxidant인 butylated hydroxyanisole (BHA)과 ascorbic acid는 세포사망과 HO-1의 발현 유도를 차단하지 않았다. 이와 같은 결과들은 PGA₂는 산화성 손상에 의해서가 아니라 PGA₂의 thiol-reactivity에 의하여 apoptosis와 HO-1의 발현을 유도하며, HO-1의 발현은 PGA₂에 의한 apoptosis와는 독립적인 현상이거나 기능적으로 apoptosis 유도의 하부에 위치하고 apoptosis의 진행에는 기여하지 않을 것이라는 것을 시사해 준다. Prostaglandin A₂ (PGA₂), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. PGA₂-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas H₂O₂-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by PGA₂. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that PGA₂ induces both apoptosis and HO-1 expression, which are critically related to the thiol-reactivity of PGA₂, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by PGA₂ without contribution to apoptosis progression.

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.

Clinicopathological role of kidney injury molecule-1 in immunoglobulin A nephropathy

( Yu Ho Lee ),( Yang-gyun Kim ),( Sang-ho Lee ),( Ju-young Moon ),( Kyung-hwan Jeong ),( Tae-won Lee ),( Chun-gyoo Ihm ) 대한신장학회 2014 Kidney Research and Clinical Practice Vol.33 No.3

Background: Urinary kidney injury molecule-1 (KIM-1) is an early and sensitivebiomarker of acute kidney injury, but it is unclear if it is a biomarker of chronicglomerulonephritis. We evaluated whether urinary KIM-1 levels in patients withimmunoglobulin A (IgA) nephropathy can be a marker to reflect clinicopathologicalseverity and predict the prognosis. Methods: We measured urinary KIM-1 levels in 40 patients (15 males; mean age36.6712.9 years) with IgA nephropathy and 10 healthy people (5 males; mean age37.379.6 years) as controls. The correlation of urinary KIM-1 levels with patients’clinical parameters, histological grades, and follow-up data were analyzed using themodified H. S. Lee grading system and tubulointerstitial change scores. Results: Urinary KIM-1 levels were higher in patients with IgA nephropathy thanhealthy controls (P¼0.001). Univariate and multivariate regression analyses showedthat urinary KIM-1 levels had a direct correlation with H. S. Lee grade andtubulointerstitial inflammation (P¼0.004 and P¼0.011, respectively). Conclusion: In patients with IgA nephropathy, urinary KIM-1 has a significantcorrelation with histopathologic severity.

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

제한된 적응증의 대퇴골 간부 골절에 사용된 역행적 골수정 삽입술

김성중,오창욱,인주철,김희수,전인호,경희수,박일형,김경훈 대한골절학회 2003 대한골절학회지 Vol.16 No.1

목 적 : 전향적 골수강내 고정술로는 치료가 힘들었던 대퇴골 간부 골절에 대해 역행적 골수강내 고정술을 시행한 후 그 결과를 분석하였다. 연구 대상 및 방법 : 대퇴골 간부 골절로 진단 후 슬관절에서 역행적으로 비확공성 골수강내 금속정(Unreamed femoral nail, Synthes R)으로 치료한 환자 중 최소 1년 이상 추시(평균; 21개월, 범위; 13개월-28개월)가 가능하였던 21명 24례의 환자를 대상으로 임상적, 방사선학적 평가를 시행하였다. 남자가 16명, 여자가 5명이었으며, 수술시 평균 연령은 41세(18-76세)이었다. Winquist-Hansen의 분류상 제1형이 10례, 제2형이 5례, 제3형이 3례, 제4행이 6례 이었으며, 전 례에서 동반된 골절 손상이 있었으며, 적용된 적응층에 따르면 동측 경골 골절이 8명, 동측 근위 대퇴골 골절)경부 및 전자부 골절) 5명, 동측 골반부 및 비구 골절 4명, 양측 대퇴골 골절 3명, 동측 슬관절 손상이 1명이었다. 방사선 소견상 골유합 시기 및 불유합, 부정유합 등을 평가하였고, 임상적 평가는 슬관절의 동통을 포함한 Neer 등에 의한 방법을 이용하였다. 결 과 : 대부분(87.5%)에서 일차적인 골유합을 얻을 수 있었으며, 평균 골유합 기간은 15.8주(범위; 12-20주)이었다. 추가적인 술식이 요구된 지연유합 또는 불유합은 3례가 있었으며, 그 외 ㎝ 이상의 단축이나 10도 이상의 부정유합 술 후 슬관절 감염 또는 불안정성이 발생한 경우는 없었다. 슬관절의 운동 평가에서 Neer score는 평균 86.9점으로, 모든 례에서 양호한 결과를 나타내었다. 평균 슬관절 운동영역은 120.2도 이었고, 3례에서 경미한 슬관절 동통을 나타냈다. 결 론 : 역행성 골수정은 동측 하지의 동반된 골절이나 다발성 골절이 있는 환자에서 대퇴골 간부 골절에 대하여 제한적으로 이용될 수 있는 유용한 방법으로 사료된다. Purpose : This is a retrospective study to analyze the results after retrograde intramedullary(IM) nailing in femoral shaft fractures with limited indications. Materials and Methods : Twenty-four femoral shaft fractures(21 patients) were operated with unreamed IM nail(Unreamed femoral nail, SynthesR) in a retrograde method and were followed for more than 1 years. There were 16 men and 5 women, and the mean age at index operation was 41 years (range 18-76 years). In Winquist-Hansen classifications, there were 10 of type Ⅰ, five of type Ⅱ, three of type Ⅲ, and ix of type Ⅳ. All the patients had associated fractures or injuries, and there were eight ipsilateral tibia fractures, five ipsilateral proximal femoral fractures(including neck and trochanter), four ipsilateral pelvic or acetabular fracture, three bilateral femoral fractures, and one ipsilateral knee injury according to the used indication, and clinical evaluation with Neer's criteria was done. Results : Most fracture(87.5%) were primarily united cases, and the mean time for union was 15.8% weeks(range 12-20 weeks). Three cases of delayed union or nonunion were developed, but a shortening over 1㎝ or malunion over 10 degrees angular deformity were not found. Evaluating the knee functions, the Neer score wes 86.9 in average and all the cases were above satisfactory grade. The average range of knee motion was 120.2 degrees, and the mild knee pain was developed in three cases. Conclusion : The retrograde IM nailing can be a useful option for femoral shaft fracture with limited indications, including ipsilateral fractures of other areas or multiple fractures.

IgG GM₁ 항체와 Campylobacter jejuni 항체와 관련된 급성 운동축삭형 신경병증

홍경훈,김승현,이영배,이영주,김희태,김주한,김명호 대한신경과학회 1997 대한신경과학회지 Vol.15 No.5

만성 경막하혈종의 단순 천공 배액술후 재발 및 두개강내 합병증 발생과 관련된 요인

김영규,민경수,이무섭,김동호,복원길,홍석기,김호재 충북대학교 의학연구소 2001 忠北醫大學術誌 Vol.11 No.2

연구목적: 만성 경막하혈종은 두개골 천두술및 혈종배액으로 쉽게 치료될 수 있는 예후가 양호한 질환으로 알려져 있으나, 혈종의 재발 및 합병증이 드물지 않게 발생하기도 한다. 본 연구는 두개골 천두술 및 혈종배액으로 치료받은 102예의 만성 경막하혈종 환자들을 분석하여 혈종의 재발 및 수술후 합병증과 관련된 요인들을 분석하고자 하였다. 대상 및 방법: 만성 경막하혈종으로 진단되어 두개골 천두술 및 혈종배액술법으로 본원 신경외과에서 수술치료받은 102명의 환자를 대상으로 하였고, 입원진료기록 및 방사선소견을 후향적으로 분석하였다. 재발 및 합병증의 발생과 관련된 요인으로는 수술전 환자의 나이, 의식상태, 양측성여부, 뇌실질의 위축정도, 수술후 기뇌의 양, 전신질환여부에 대하여 분석하였다. 결과: 재발의 빈도는 9.8% 였으며 재발과 관련된 요인으로는 양측성, 고령, 수술후 뇌실질재팽창정도(뇌 실질위축, 잔여수액, 기뇌)가 관계가 있었으나 환자의 예후에는 영향이 없었다. 합병증의 종류에는 수술후 급성출혈 5예 및 경막하 농양 1예가 있었으나 이는 모두 출혈성전신질환 또는 면역결핍증이 동반된 환자에서 발생하였고 예후가 불량하였으며, 긴장성 기뇌가 1예발생 하였다. 결론: 전신질환의 동반여부가 합병증의 발생 및 환자의 예후에 가장 중요한 영향을 미쳤으며, 비록 예후에는 영향이 적으나 혈종의 재발의 빈도가 드물지 않으며 기뇌의 방지 및 배액방법의 개선으로 재발의 빈도를 줄일 수 있을 것으로 생각된다. Purpose : Most of chronic subdural hematomas(SOH) are amenable disease with simple cranoistomy drainage, but the recurrence of SDH or development of complications after surgery is not uncommon. To see the prognostic factors related to outcome the recurrence of chronic subdural hematoma and development of complication were analysed in 102 cases of chronic SDH after craniostomy drainage. Materials and Methods: We studied 102 chronic SDH patients treated with craniostomy drainage. Clinical and radiological records were reviewed retrospectively. We analysed the recurrence and complication rate, factors related to the development of recurrence and complications. Results: The rate of recurrence of chronic SDH was 9.8% and factors related to recurrence were bilaterality, old age, and postoperative intracranial environments for brain reexpansion(degree of brain atrophy, amount of residual fluid, amount of intracranial air). Intracranial complications after surgery were developed in 7 cases(6.9%), 5 postoperative bleedings, 1 tension pneumocephalus, 1 subdural empyema. Conclusion : Preoperative clinical condition and association of serious sytemic disease were of major importance in prognosis. The recurrence of chronc SDH was not uncommon, Even though the recurrence was not related to the outcome, great care should be paid on the patients with high risk group.