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Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9
<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>
<P>The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (<I>SASP</I>) genes (interleukin [IL]-1β, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrow–derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway.</P>
목적: 알코올성 간질환에서의 대사성 산증은 지속적인 과량의 알코올 섭취로 인한 당 신생 합성의 억제와 BOHB/AcAc 비율의 증가, 단기간의 금식으로 인한 저혈당, 인슐린 분비 저하, 유리 지방산과 케톤체 형성의 증가, 구토와 수분 섭취 부족에 의한 심한 탈수에 의해 발생하는 것으로 알려져 있다. 알코올성 케톤산증과 감별할 질환으로는 당뇨병성 케톤산증, 젖산증, 살리실레이트, 메탄올, 에틸렌글리콜 중독 등이 있다. 본 연구는 대사성 산증을 동반한 알코올성 간질환으로 내원하여 입원한 환자들을 대상으로 생존군과 사망군에서 임상적 양상 및 검사 소견들의 차이를 비교하여 단기 예후와 연관 있는 인자들을 알아보고자 하였다. 대상과 방법: 만성 알코올 남용자이면서 대사성 산증을 동반하여 입원한 알코올성 간질환 환자 29명을 생존군(18명)과 사망군(11명)으로 나누어 임상 소견과 검사실 소견을 비교하였다. 결과: 1) 대상 환자군은 연령은 36-65세였으며, 성별은 남자가 26명이었고 여자가 3명이었다. 2) 임상 증상은 의식저하, 복통, 구토, 호흡 곤란, 토혈, 흉통 등 다양하게 나타났으며, 신체검사 소견은 탈수, 황달, 빈혈, 간비대, 복수, 부종 등이었고 두 집단을 비교했을 때 사망군에서 복수가 유의하게 더 많은 빈도로 관찰되었다. 일일 평균 음주량은 사망군에서 유의하게 더 많았고(198 vs. 123, P=0.034) 음주 기간과 총 음주량은 두 군 간에 유의한 차이를 보이지 않았다. 4) 내원시 혈액검사 소견을 비교하였을 때 사망군에서 동맥혈 산염기 차이가 유의하게 낮았고 헤모글로빈, 혈소판도 유의하게 낮았다. 사망군에서 총 비리루빈, 크레아티닌, 무기인, 암모니아가 유의하게 높았고 알부민, 클로라이드가 유의하게 낮았다. 사망군에서 프로트롬빈 시간이 유의하게 연장되었으며 섬유소원은 유의하게 낮았고 D dimer는 유의하게 높았다. 결론: 대사성 산증을 동반한 알코올성 간질환 환자에서 일일 알코올 섭취량을 파악하고 복수의 유무, 동맥혈 산염기 차이, 헤모글로빈, 혈소판, 총 빌리루빈, 알부민, 크레아티닌, 무기인, 클로라이드, 암모니아, 프로트롬빈 시간, 섬유소원, D dimer 등을 검사하는 것이 단기 예후를 예측하는 데 도움이 될 것으로 사료된다. 향후 많은 환자들을 대상으로 하여 예후 관련 인자들에 대한 전향적이고 체계적인 연구가 요망된다. Background/Aims: Alcoholic liver disease with metabolic acidosis may have possible causes such as alcoholic ketoacidosis, diabetic ketoacidosis, lactic acidosis. Salicylate, methanol, and ethylene glycol intoxication should also be considered. The aim of this study was to investigate the short-term prognostic factors in patients with alcoholic liver disease with metabolic acidosis. Methods: Clinical data related to twenty-nine patients with alcoholic liver disease and metabolic acidosis was analysed retrospectively. Patients were divided into two groups according to the outcome (survival or death). Past medical history, and physical, laboratory and radiologic data at admission were compared. Results: The amount of daily alcohol intake differed significantly between the two groups (P=0.034), but duration and total amount of alcohol intake did not differ significantly between the two groups (P=0.128; P=0.360). The presence of ascites differed significantly between two the groups (P=0.019). On laboratory testing, the following differed significantly: base excess (P=0.038), hemoglobin (P=0.019), platelet (P=0.040), total bilirubin (P=0.007), albumin (P=0.012), creatinine (P=0.014), phosphorus (P=0.021), chloride (P=0.010), ammonia (P=0.003), prothrombin time (P=0.033), fibrinogen (P=0.011) and D-dimer (P=0.024). Review of the medical history of the patients showed diabetes (10/29), cirrhosis (10/29), and hepatocellular carcinoma (1/29). Combined conditions at admission were sepsis (8/29), pneumonia (7/29), acute renal failure (6/29), rhabdomyolysis (5/29), gastrointestinal hemorrhage (4/29), acute pancreatitis (3/29), acute respiratory distress syndrome (2/29), and acute myocardial infarction (1/29). Conclusions: The amount of daily alcohol intake, base excess, hemoglobin, platelet, total bilirubin, albumin, creatinine, phosphorus, chloride, ammonia, prothrombin time, fibrinogen and D-dimer seemed to be useful parameters in predicting short-term prognosis of patients with alcoholic liver disease with metabolic acidosis. Further study is needed to define the significance of these factors. (Korean J Hepatol 2004;10:117-124)
Recently, the diet of middle aged Korean men is changing. Instead of eating Korean foods exclusively, they are consuming more Western foods which are often unhealthy. In addition, they are exercising less. These factors are leading to a rise in lifestyle related disease, such as diabetes, and dangerous medical conditions like hypertension. As a result, some middle aged men have taken up light exercise, such as hiking, walking, swimming etc. However, they don't know how to set up an exercise program, i.e. frequency of exercise, intensity, duration, etc. A 15 week exercise class was set up 36 middle aged men. Before the class began, a physical fitness and blood test were administered to each subject. The same tests were repeated after the 15th week. Based on the initial results, individual programs were prepared for each participant. A step calorie counter was supplied to measure their exercise activity. The step count results were checked everday, and based on the results, the subjects were divided into three groups for analytical purposes. The firts group, sixteen subjects(44%), averaged a little over 8,000 steps per day. The second group, eight subjects(22%), averaged between 8-10,000 steps per day. The third group, twelve subjects(33%), averaged a little over 10,000 steps per day. After fifteen weeks, the total cholesterol, HDL cholesterol and LDL cholesterol of all subjects showed no significant change. The second and third group showing an especially marked decrease in blood sugar. Also, physical fitness improved for the second and third groups. In conclusion, both groups doing the most exercise showed improvement in their TG and blood sugar results. Blood pressure also decreased for these two groups, which was not true for the first group, also, physical fitness improved in the second and third groups, while the first group showed no significant change. It appears that exceeding a certain minimum level of exercise is required to achieve good results. What would happen if group 1 did the same exercise for longer than is weeks.
The object of this study is to obtain a fundamental data on the food and nutritive components of wild fresh water Mud-turtle, Amyda-sinensis, propduced in Korea.For this purpose, the food components in each portion such as the layer of fat, blood and total flesh were investigated and compared by the distinction of sex, respectively.Th results obtained are summarized as follows : 1.Proximate compositions of total flesh between the female and male were nearly the same on the whole, as the contents of moisture, crude protein, crude fat, total sugar and crude ash were 78.4-80.1%, 16.8-18.7%, 1.5-1.6%, 0.3-0.4%, 1.1%, respectively. Protein-N occupied 89%, 91% of total nitrogen content, respectively. 2.The analysis of free amino acids showed that histidine, methionine and arginine were major amino acids in the flesh extract of female, having 32.7% (546.30mg%), 28.8%(481.44mg%),19.7%(329.72mg%) on dry basis, and that histidine, methionine, serine were major in the male, having 34.6% (360.45mg%),28.6% (298.39mg%),8.2% (85.18mg%) of total free amino acid contents, respectively. While the other free amino acid contents except threonine and proline in trace of undetected amount were relatively poor by the content ratio of 0.2-5.3%. 3.The content of lysine in total flesh of the female and male seemed to be marked differences, being 13.5%(2415.73mg%) and 9.3%(1465.37mg%) respectively, but the other amino acid compositions of the female showed similar tendency to that of the male without significant differences. The major amino acids were glutamic acid (16.3-17.7%), lysine (9.3-13.5%), aspartic acid (7.6-8.7%) leucine (7.7-8.3%), alanine (5.8-6.2%) and arginine (5.6-6.0%) occupied 56.2-56.5% of total amino acids, but such amino acid contents as proline, threonine glycine, valine, phenylalanine, serine, isoleucine, tyrosine, methionine and histidine were low in order, while cystine and tryptophan were least amount. The essential amino acid content of 8 kinds occupied 38.0-43.2% (2471.92-2832.72mg/gN) of total amino acids. 4.Among the 9 kinds of minerals analyzed such as total flesh and blood, mineral compositions in the female showed similar to the pattern in the male. Such macrominerals as potassium, magnesium, sodium and phosphorus contents in flesh were absolutely predominant being more than 98.0% (498.5-521.6mg%), these four elements in blood also occupied 92.7-94.1% (498.1-551.6mg%) of total minerals, while iron content of micromineral in blood 5.3-6.8% (31.0-36.4mg%). 5.Fatty acid compositions in total lipid were different considerably by the distinction of sex and each portion except layer of fat. The major fatty acids of flesh in the female and male were shown to be C18 : 1(1425.7%), C16 : 0(13.5-18.6%), C18 : 3(9.0-17.4%), C16 : 1(13.4-16.4%), and particulary C18 : 2(20.0%), C14 : 1(16.5%) in the male.In fresh blood of the female and male, C18 : 1(16.3-36.7%), C16 : 1 (16.2-18.5%), C18 : 3 (13.7-17.3%), C16 : 0(8.5-9.6%) were the most abundant fatty acids, and particulary C14 : 1(10.1%), C18 : 2(9.1%) in the male. In the layer of fat, the major fatty acids were C18 : 1(25.2-28.0%), C16 : 0(17.2-18.3%), C16 : 1 (15.8-17.0:7), C18 : 3 (10.5-11.6%) and C18 : 2(8.8-9.7%).Total lipids consisted of 18.3-32.5% of saturated fatty acids, 42.6-60.6% of monoene and 19.2-29.2% of polyene acids to total fatty acids, respectively, and P/S ratio in each fortion were in sphere of 0.7-1.2.
Background : Widespread resistance to the broad-spectrum tetracyclines has been caused by heavy clinical use and misuse in the human population. Additional contributing factors are the use of tetracyclines as a growth promotor in agriculture and as infection control agent in domestic animals and aquaculture. The purpose of this study was to investigate susceptibility of tetracycline and to detect tetracycline resistant genes from chickens. Methods : Thirty-seven tetracycline resistant enteric bacteria were collected from the rectal swab of chickens by disk diffusion method, and the MICs (minimal inhibitory concentration) of tetracycline, oxytetracycline, chlortetracycline and erythromycin were determined by agar dilution method. PCR screening was carried out to identify possible tet genes that contributed to tetracycline resistance. Results : Of the 37 tetracycline-resistant isolates, the frequency of isolation was Escherichia coli 32 (84.2%), Citrobacter freundii 2 (5.3%), Klebsiella pneumoniae 1 (2.5%), Lectercia adecarboxylata 1 (2.5%), Proteus vulgaris 1 (2.5%). The MIC range for the tetracycline-resistant enteric bacteria was as follows: tetracycline, >256 ㎍/㎖; oxytetracycline, >256 ㎍/㎖; chlortetracycline, 16∼>128 ㎍/㎖; erythromycin, 32∼>256 ㎍/㎖. All of the 37 tetracycline-resistant isolates were positive for tet(A) gene (100%), and 8 (21.6%) of these isolates were found to harbor the tet(A) plus tet(B) genes. Conclusion : All isolates were resistant to tetracycline, oxytetracycline, chlortetracycline and erythromycin, and they harbored tet(A) gene or tet(A) plus tet(B) genes that gave rise to the tetracycline resistance. These results show that enteric bacteria isolates from chicken in Korea are resistant to tetracycline and all of them harbored tet(A) gene.