Study of decreased melanin production through p53 by heme oxygenase-1 inhibitor in normal human melanocytes

( Hee Sun Lim ),( Sun A Jin ),( Jee Bum Lee ),( Seong Jin Kim ),( Seung Chul Lee ),( Young Ho Won ),( Sook Jung Yoon ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Heme oxygenase (HO)-1 is induced by oxidative stress and plays important roles in anti-apoptosis and the rapid growth of several solid tumors. p53 has a central role in skin pigmentation and may impact onmelanoma at all stages. However, there has been little study of HO-1 in relation with p53 on melanin production Objectives: To know the effect of HO-1 on melanogenesis through p53 in normal human melanocytes Methods: Human melanocytes (hM) were primarily cultured from foreskin. After incubation, cells were rinsed twice with PBS then transfection with p53 siRNA Results: Melanin content was detected with ELISA and Western blot analysis and RT-PCR of tyrosinase, MITF were performed after ZnPP treatment and p53 transfection. After ZnPP treatment, melanin content was decreased, and tyrosinase and MITF protein levels were decreased. Tyrosinase and MITF mRNA levels were also decreased. However, melanin content and tyrosinase and MITF protein levels were increased after CoPP treatment. After p53 transfection, HO-1 expression was decreased when HO-1 stimulator was treated. In addition, melanin content was decreased, and tyrosinase expression was decreased in Western blot analysis Conclusion: These results suggest that melanogenesis is inhibited by ZnPP by decreased melanin production, tyrosinase and MITF protein and mRNA levels. Furthermore, those inhibitory effects of ZnPP may be dependent on p53 in normal human melanocytes. Therefore, HO-1 may play an important role in melanogensis

Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

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.

췌장 선방세포암 1예

이화정,지준호,박승찬,박정철,최은정,서혜진,이원식,이정림,배병조,손경락,이경희 영남대학교 의과대학 2008 Yeungnam University Journal of Medicine Vol.25 No.2

Acinar cell carcinoma is a rare tumor that represents 1~2% of al1 pancreatic cancers. Clinical and radiologic findings are inconclusive in this disease Acinar cell carcinoma is characterized by rapid progression and early metastasis, which lead to its poor prognosis. A 41-year-o1d man was admitted to our hospital for abdominal pain. Abdominal computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) showed a splenic mass, which was being invaded by a pancreatic tail mass and which had increased ^(18)F-fluorodeoxyglucose (FDG) uptake Primary radical distal pancreatectomy and splenectomy were performed. Pathologic findings revealed an acinar cell carcinoma of the Pancreas The patient underwent a total gastrectomy three months later because of gastric recurrence Four months later, multiple hepatic metastases were discovered, and the patient underwent a left hepatectomy During treatment with capecitabine, there was no evidence of tumor progression for 14 months. We report a case of metastatic pancreatic acinar cell carcinoma, which did not progress for an extended period while the patient was being treated with capecitabme.

원발성 후복막 점액낭샘암종 1예

지준호,이화정,박승찬,박정철,최은정,서혜진,이원식,이정림,배병조,손경락,이경희 영남대학교 의과대학 2008 Yeungnam University Journal of Medicine Vol.25 No.2

Primary retroperitoneal mucinous cystadenocarcinoma is a very rare malignancy, and little is known concerning its Pathogenesis, optimal treatment, and prognosis. A 29-year-o1d pregnant woman (21 weeks) Presented with abdominal discomfort CA 19-9, CA 125, and CEA were normal Abdominal CT scanning revealed a 19x15x13 cm retropentoneal tumor Exploratory laparotomy and tumor excision were performed. Mucinous retropentoneal implants were removed as completely as possible Histologically, the tumor showed focal areas of capsular invasion, but free resection margins The uterus and both ovaries were normal in appearance No adjuvant therapy was pursued. Six months later, Peritoneal and bilateral ovarian metastases were discovered. Hence, we report the details of this case of primary retroperitoneal mucinous Cystadeno-carcinoma and present a review of the literature.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

Lee, Young-Man,Auh, Q-Schick,Lee, Deok-Won,Kim, Jun-Yeol,Jung, Ha-Jin,Lee, Seung-Ho,Kim, Eun-Cheol Hindawi Publishing Corporation 2013 BioMed research international Vol.2013 No.-

<P>Although previous studies have shown that mollugin, a bioactive phytochemical isolated from <I>Rubia cordifolia</I> L. (Rubiaceae), exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs). Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G<SUB>1</SUB> phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-<I><I>κ</I></I>B and NF-<I><I>κ</I></I>B-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl), invasion (MMP-9 and ICAM-1), and angiogenesis (FGF-2 and VEGF). Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1) and nuclear factor E2–related factor 2 (Nrf2). Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-<I><I>κ</I></I>B.</P>

류마티스 관절염 병이에서 제2형콜라겐에 대한 면역반응의 역할

정영옥,황승재,김호연 Official Journal of the Korean society for immunol 2003 Immune Network Vol.3 No.1

실험동물에서의 내분비계 교란물질인 DEHP, DBP의 생체내 영향

정지윤,이성호,박영석,박병권,김병수,김상기,박창식,강경선,이영순 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

The major protocol features of the rodent uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. The rodents were ovariectomized under general anesthesia via bilateral flank incisions and randomly assigned to groups of 5 animals. This study investigated the estrogenic effects of phthalates, which are DEHP and DBP, suspected as endocrine disruptors. It is concluded that three daily subcutaneous administration of test chemicals, which are di-ethylhexyl phthalate(DEHP) and di-n-butyl phthalate(DBP), to 9 week-old rodents. The results revealed that DEHP & DBP show similar uterotrophic activity in the rat and the mouse, using subcutaneous administration. DEHP and DBP failed to affect any of these parameters, which are body weight, mammary gland, vaginal and uterus histopathology. but, DBP increased uterus weight to only one rat of 1.0 g/kg group. The results conform the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.

Multi-Agent System을 이용한 배전계통 자율 적응 최적 보호 시스템

鄭廣鎬,崔勉松,李承宰 明知大學校 産業技術硏究所 2004 産業技術硏究所論文集 Vol.23 No.-

The topology of the power distribution network with protection scheme using over current relay is changed frequently because of load change, maintenance, mending and so on, but the setting values of protective devices are maximum values to ignore load and topology changes of the distribution network. Therefore the protection system can't isolate the light fault from distribution system. Currently, multi-agent system is focused one's attention on the world. And also the protective device is made by digital component and it has communication ability through the influence of communication technology. Because of these reasons, "an adaptive optimal protection of a distribution system network using multi-agent system" is proposed to apply multi agent system for automatic operation of protective system in this paper. The characteristic of multi-agent system has autonomy that is self-start ability and intelligence, with own knowledge, reasoning and judging ability. The agent works together to achieve a global goal, in which case each agent does the given job only. A protective agent of the proposed system has two autonomous functions with basic the protective function. One is the detecting function of network change. The other is the resetting function for optimal protection of a distribution system by coordinating with neighbor agents. When the fault is detected on network, agents isolate fault from network, then it sets parameters to new operation conditions by collaborating with other device agents. This system has adaptive protection with optimization "Protectability" applying protection. It is the "Protectability" concept for evaluation of protection system to describe how the system is well protection by an index numerical value. This system can operate optimal protection, because it detects adequate parameter by optimal method based on collaboration with neighbor agent. The purpose of proposed paper is development of system which has automatic detection of network change and rapidly automatic adaptation against network change with optimal method to set adequate parameter for complete protection.