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      • 몰핀이 신경아세포종 SH-SY5Y 세포에서 Peroxynitrite에 의한 세포고사를 막는 것은 아편양 수용체나 Phosphatidylinositol-3 kinase (PI-3 kinase) 경로의 활성화에 의한 것이 아니다

        정영표,이동렬,손용,김태요,윤재승,송윤강,김명선,박래길 圓光大學校 醫科學硏究所 1999 圓光醫科學 Vol.15 No.2

        Background: The effect of opioids on nitric oxide (NO)- and peroxynitrite-induced neuronal cell death is largely unknown. In the present study, we examined the effect of morphine on NO- and peroxynitrite-induced cell death using a human neuroblastoma SH-SY5Y cell line, which abundantly expresses μ, δ, k-opioid receptors. Methods: The cultured cells were pretreated with morphine and exposed to 3-morpholinosydnonimine (SIN-1) that simultaneously generates NO and superoxide, thus possibly forming peroxynitrite. The cell damage was assessed by using MTT assay ana crystal violet staining. Exposure of the cells to SIN-1 for 24 hours induced apoptotic cell death, as evaluated by the occurrence of morphological nuclear changes characteristics of apoptosis using 4', 6-diamidino-2-phenylindole (DAPI) and measurement of pro-apoptotic protease, caspase-3, activity. Results: Pretreatment of SH-SY5Y with morphine, significantly inhibited the apoptotic cell death in a dose-dependent manner. Morphine also inhibited SIN-1-induced proapoptotic protease, caspase-3, activity in a dose-dependent manner. However, naloxone (20 μM) hardly antagonized the effect of morphine in SIN-1-induced cell death. The selective ligands for opioid receptor subtypes, [D-Ala^2, N-Me-Phe^4, Gly-ol^5]enkephalin (DAMGO, μ-opioid receptor agonist), [D-Pen^2.5]enkephalin (DPDPE, δ-opioid receptor agonist) and U-69593 (k-opioid receptor agonist) at the concentration of 10 μM did not prevent the cell death induced by SIN-1. PI3-kinase inhibitors, Wortmannin and LY294002, did not inhibit the action of morphine on apoptotic cell death. The neuroblastoma cells treated with morphine significantly elevated glutathione levels (GSH). Conclusions: The present study showed that morphine protected human neuroblastoma cell line, SH-SY45Y, from the peroxynitrite-induced apoptotic cell death through elevated GSH levels. However, it is suggested that the elevation of GSH by morphine is not via the activation of opioid receptors and/or PI3-kinase pathway but via other unknown mechanism.

      • 한의진단명과 진단요건의 표준화 연구 III : 3차년도 연구결과 보고

        최선미,양기상,최승훈,박경모,박종현,심범상,김성우,노석선,이인선,정진홍,이진용,김달래,임형호,김윤범,박성식,송태원,김종우,이승기,최윤정,신순식 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

        The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the third year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows : - analyzing and differentiating of epidemic febrile disease - analyzing and differentiating in accordance with the Sasang constitution medicine based on four-type recognition - differentiation of disease according to pathological changes of Chong and Ren channels - standards for diagnosis of women's disease - standards for diagnosis of children's disease - standards for diagnosis of motor and sensor disturbance (-muscle. born, joint, etc.) - standards for diagnosis of neuropsychiatric disease - standards for diagnosis of five sense organ disease - standards for diagnosis of external disease The indivisual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name, notion of diagnosis pattern, index of differentiation of symptoms and signs, the main point of diagnosis, analysis of diagnosis pattern, discrimination of diagnosis pattern, prognosis, a way of curing a disease, prescription, herbs in common use, disease appearing the diagnosis pattern, documents. The standards for diagnosis of each disease was arranged by the diagnostic requirements in the following order : another name, notion of disease, the main point of diagnosis, analyzing and differentiating of disease, analysis of disease, discrimination of disease, prognosis, a way of curing and prescription of disease, disease in western medicine appearing the disease in oriental medicine, documents.

      • SCISCIESCOPUS

        p21-Activated Kinase 4 Critically Regulates Melanogenesis via Activation of the CREB/MITF and β-Catenin/MITF Pathways

        Yun, Cheong-Yong,You, Soon-Tae,Kim, Jin-Hwa,Chung, Jin H,Han, Sang-Bae,Shin, Eun-Young,Kim, Eung-Gook The Society for Investigative Dermatology, Inc 2015 The Journal of investigative dermatology Vol.135 No.5

        p21-activated kinase 4 (PAK4) regulates a wide range of cellular events, including cytoskeletal remodeling, cell growth, and survival. Our previous study identified PAK4 as a key regulator of cAMP-response element–binding protein (CREB) that acts upstream of microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. We therefore investigated the role of PAK4 in melanogenesis. Melanocytes express both PAK2 and PAK4 isoforms, but only RNA interference knockdown of PAK4 significantly influenced α-melanocyte-stimulating hormone (α-MSH)–induced melanogenesis in B16 melanoma cells. Consistent with this result, PAK4 inhibition by PF3758309, a potent ATP-competitive inhibitor of PAKs, suppressed not only α-MSH–induced melanogenesis in B16 melanoma and human epithelial melanocyte cells but also UVB-induced melanogenesis in the skin of melanin-possessing hairless mice (HRM-2) in a dose-dependent manner. Inhibition of PAK4 over several days markedly decreased the levels of CREB, MITF, and tyrosinase in both HRM-2 mice and B16 melanoma cells. Moreover, PAK4 knockdown and inhibition suppressed α-MSH-stimulated β-catenin phosphorylation at serine 675 (S675) but enhanced phosphorylation at S33/37, an indicator for ubiquitination-dependent proteolysis. Together, our results provide evidence that PAK4 promotes α-MSH/UVB-induced melanogenesis via the CREB and Wnt/β-catenin signaling pathways and suggest that PAK4 may be a potential therapeutic target in pigmentation disorders.

      • KCI등재후보

        직업적 아크릴아미드 폭로에 의한 다발성 신경병증

        정해관,권용욱,어경윤,김병준,양정선,정철,진영우,이미영,강성규 大韓産業醫學會 1998 대한직업환경의학회지 Vol.10 No.3

        Authors report a first Korean case of polyneuropathy in an acrylamide producing factory together with an environmental and epidemiologic survey for the ten workers of the same workplace and 46 workers in the production and manufacturing acrylamide in Ulsan, Korea. The case is 30 years old man who worked in the production of the acrylamide for two years. In August, 1997, he had a weakness of the lower extremity with loss of body weight of 15 Kg which progressed to paresthesia of the limbs, the loss of vibration sense, difficulty in walking, speech disturbance, dysuria, constipation, difficulty in erection and swallowing difficulty. Neurologic examination showed a complete loss of vibration and position sense, and loss of deep tendon reflex in all the limbs. There was a contact dermatitis-like skin lesion on the feet. Electrodiagnostic test showed a generalized polyneuropathy of moderate degree involving motor and sensory component of peripheral and cranial nerves. After 8 months' cessation from exposure and supportive care, his symptoms were completely resolved, but abnormality in electrodiagnostic test and vibrotactile perception threshold still persisted, although much improved than before. There were 11 workers in the same workplace of the case, producing acrylamide by microorganism as a catalyst. Environmental monitoring of the workplace revealed air borne concentration of the acrylamide to be from 0.05 to 0.23 mg/m3 by personal sampling and from 7.65 to 11.65 mg/m3 by area sampling during filter exchanging process, which far exceeds TLV-TWA of 0.03 mg/m3. However, acrylamide was not detected from the plasma of the workers. Symptom questionnaire showed a markedly higher complain of neurologic symptoms, compared to the workers of the other acrylamide producing companies. Electrodiagnostic test showed a several workers are in the lower normal range without definite abnormality. Vibrotactile perception threshold by Vibratron Ⅱ showed a significantly increased threshold in the workers of the same workplace compared to the other acrylamide workers and significantly decreased test score of color vision compared to normal controls. After improvement of the production process and strict wearing of the protective device, most workers reported the improvement of clinical symptoms, but vibrotactile perception threshold was not improved. These result suggests the need for the effective environmental monitoring together with a periodic biological monitoring. Development of effective screening test is urgently needed to control and assess the skin absorption of acrylamide.

      • KCI등재후보

        전화번호안내원의 누적외상성 장애

        정해관,최병순,김지용,유선희,임현술,김용민,어경윤,권용욱 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.1

        To evaluate the prevalence of cumulative trauma disorders in relation to ergonomic evaluation of their work, 260 female directory assistance operators employed in three branch facilities of the nation-wide telecommunication company. Ergonomic evaluation of the work status was done by two industrial hygienists through inspection. Workers were surveyed with standardized self-administered questionnaire and examined by family physicians and an orthopaedician for cumulative trauma disorders. Laboratory examination of serum aspartate aminotransferase(AST), creatinine phosphokinase(CPK), aldolase and rheumatoid factor was done and X-ray of cervical spine and both shoulders was taken from all subjects and nerve conduction velocity test was done on 57 subjects with suspected nerve entrapment cases. Cumulative trauma disorders were categorized into 3 category according to work-relatedness of the disorders. On ergonomic evaluation of the working posture and work environment, improvement of work posture revealed inappropriate postures and devices. Mean age of the subjects were 39 years old and more than 80% graduated high school or above. Ninety-eight percent of the workers employed in the company for more than 15 years and 74.6% of the workers worked at the VDT job for more than 4 years. Mean daily work hours was 8.0 hours per day and mean break hours was 90.5 minutes per day with mean extra work hours of 10.7 hours per month. Mean daily calls were 1128.6 calls in maximum and 864-8 calls in minimum. On laboratory examination, 13.(5.0%) workers had abnormal AST, 53(20.4%) had abnormal CPK, and 1(0.4%) had abnormal aldolase level. On x-ray examination of cervical spine, 111(42.7%) had loss of or reversed normal cervical lordosis, 10(3.8%) had narrowing of intervertebral space. Nerve conduction velocity test was abnormal in 11(19.2%) among 57 workers. Among disorders categorized as work-related, 131(50.4%) were diagnosed to have fatigue myalgia of levator scapulae, 108(41.5%) had cervical strain or sprain, 47(18.1%) had fatigue arthralgia of phalangeal joints, and 47(18.1%) had probable carpal tunnel syndrome, in 10(3.8%) of those diagnosis was confirmed electrophysiologically. Age, seniority, work duration at present job, workload nor location of facilities were associated with the prevalence of symptoms nor specific diagnoses on simple statistical analysis and multiple logistic regression, which seems to be due to highly selected and homogeneous characteristics of the study subjects. Above results shows that cumulative trauma disorders are very prevalent among directory assistance operators and elaborate effort is needed to reduce the cumulative trauma disorders among the operators.

      • Hebei Spirit Oil Spill Exposure and Subjective Symptoms in Residents Participating in Clean-Up Activities

        Cheong, Hae-Kwan,Ha, Mi-Na,Lee, Jong-Seong,Kwon, Ho-Jang,Ha, Eun-Hee,Hong, Yun-Chul,Choi, Ye-Yong,Jeong, Woo-Chul,Hur, Jong-Il,Lee, Seung-Min,Kim, Eun-Jung,Im, Ho-Sub The Korean Society of Environmental Toxicology 2011 환경독성보건학회지 Vol.26 No.-

        Objectives: This study was conducted to examine the relationship between crude oil exposure and physical symptoms among residents participating in clean-up work associated with the Hebei Spirit oil spill, 2007 in Korea. Methods: A total of 288 residents responded to a questionnaire regarding subjective physical symptoms, sociodemographic characteristics and clean-up activities that occurred between two and eight weeks after the accident. Additionally, the urine of 154 of the respondents was analyzed for metabolites of volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) and heavy metals. To compare the urinary levels of exposure biomarkers, the urine of 39 inland residents who were not directly exposed to the oil spill were analyzed. Results: Residents exposed to oil remnants through clean-up work showed associations between physical symptoms and the exposure levels defined in various ways, including days of work, degree of skin contamination, and levels of some urinary exposure biomarkers of VOCs, metabolites and metals, although no major abnormalities in urinary exposure biomarkers were observed. Conclusions: This study provides evidence of a relationship between crude oil exposure and acute human health effects and suggests the need for follow-up to evaluate the exposure status and long-term health effects of clean-up participants.

      • 항Ro(SS-A) 및 항La(SS-B)항체 양성인 전신성 경피증 환자에서 태어난 환아로 선천성 완전 심장차단을 가졌던 1례

        정광호,남경재,이윤우,박용원 인제대학교 1994 仁濟醫學 Vol.15 No.4

        선천성 완전 심장차단의 중요한 원인 중의 하나는 모체의 항 Ro(SSA) 항체가 태반을 통과하는 것이다. 26세의 항 Ro(SSA) 항체 및 항 La(SS-B) 항체가 양성인 전신성경피증 산모로부터 태어난 18개월된 여아에게서 선천성 완전 심장 차단을 관찰하였기에 보고하는 바이다. One of the important causes of congenital heart block is the transplacental transmission of maternal ants-Ro(SSA) antibody. An 18 month old girl was brought to our hospital because of dyspnea from which she had been suffered after birth. A complete heart block, atrial septal defect(secundum type) and patent ductus arteriosus were found. Closure of defects was done and permanent pace maker installed. She died of pneumonia and congestive heart failure at the age of 30 months. Her mother had this baby at the age of 26 years old and had suffered from systemic sclerosis since her early twenties. The laboratory studies on her revealed as follows. ANA 1 : 2650, anti-nRNP Ab (-), anti-Scl 70 Ab (-), anti-centromere Ab (-), rheumatoid factor (-), anti-Ro(SSA) Ab (+), anti-La(SSB) Ab (+), interstitial pulmonary fibrosis (DLCO : 50% of predicted value).

      • SCIESCOPUSKCI등재

        Effect of Hydride Reorientation on Delayed Hydride Cracking In Zr-2.5Nb Tubes

        Yun Yeo Bum,Kim Young Suk,Im Kyung Soo,Cheong Yong Moo,Kim Sung Soo Korean Nuclear Society 2003 Nuclear Engineering and Technology Vol.35 No.6

        The objective of this study is to investigate the reorientation of hydrides with applied stress intensity factor, the peak temperature and the time when to apply the stress intensity factor in a Zr-2.5Nb pressure tube during its thermal cycle treatment. Cantilever beam (CB) specimens with a notch of 0.5 mm in depth made from the Zr-2.5Nb tube were subjected to electrolytic hydrogen charging to contain 60 ppm H and then to a thermal cycle involving heating to the peak temperature of either 310 or $380^{\circ}C$, holding there for 50 h and then cooling to the test temperature of $250^{\circ}C$. The stress intensity factor of either 6.13 or $18.4\;MPa\sqrt{m}$ was applied at the beginning of the thermal cycle, at the end of the hold at the peak temperatures and after cooling to the test temperature, respectively. The reorientation of hydrides in the Zr-2.5Nb tube was enhanced with the increased peak temperature and applied stress intensity factor. Furthermore, when the CB specimens were subjected to $18.4\;MPa\sqrt{m}$ from the beginning of the thermal cycle, the reoriented hydrides occurred almost all over the Zr-2.5Nb tube, surprisingly suppressing the growth of a DHC crack. In contrast, when the CB specimens were subjected to the stress intensity factor at the test temperature, little reorientation of hydrides was observed except the notch region, leading the Zr-2.5Nb to grow a large DHC crack. Based on the correlation between the reorientation of hydrides and the DHC crack growth, a governing factor for DHC is discussed along with the feasibility of the Kim's DHC model.

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