• BMB Reports
• /
• 제39권3호
• /
• pp.304-310
• /
• 2006

Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of Phase II detoxifying enzymes and antioxidant enzymes in response to many cancer chemopreventive compounds. In this study, we investigated the role of receptor associated coactivator (RAC3) or steroid receptor coactivator-3 (SRC3) and other nuclear co-regulators including CBP/p300 (CREB-binding protein), CARM1 (Coactivator-associated arginine methyltransferase), PRMT1 (Protein arginine methyl-transferase 1), and p/CAF (p300/CBP-associated factor) in the transcriptional activation of a chimeric Gal4-Nrf2-Luciferase system containing the transactivation domain (TAD) of Nrf2 in HepG2 cells. The results indicated that RAC3 up-regulated the transactivation activity of Gal4-Nrf2-(1-370) in a dose-dependent manner. The enhancement of transactivation domain activity of Gal4-Nrf2-(1-370) by RAC3 was dampened in the presence of dominant negative mutants of RAC3. Next we studied the effects of other nuclear co-regulators including CBP/p300, CARM1, PRMT1 and p/CAF, and the results showed that they had different level of positive effects on this transactivation domain activity of Gal4-Nrf2-(1-370). But importantly, synergistic effects of these co-regulators in the presence of RAC3/SRC3 on the transactivation activity of Gal4-Nrf2-(1-370) were observed. In summary, our present study showed for the first time that the 160 RAC3/SRC3 is involved in the functional transactivation of TAD of Nrf2 and that the other nuclear co-regulators such as CBP/p300, CARM1, PRMT1 and p/CAF can also transcriptionally activate this TAD of Nrf2 and that they could further enhance the transactivation activity mediated by RAC3/SRC3.

• 한국환경농학회지
• /
• 제18권1호
• /
• pp.41-47
• /
• 1999

NaCl과 방사선이 자주달개비 수술털 세포 분홍돌연변이에 미치는 영향을 조사하였다. 포트에서 생육된 Tradescantia 4430 식물체에 코발트 선원으로부터 0.3, 0.5, 1.0 및 2.0Gy의 감마선을 조사하였다. NaCl 용액(170mM)의 분무처리는 방사선 조사 24시간전 및 후에 이루어졌다. CT 실험군, NaCl+${\gamma}$실험군 및 ${\gamma}$+NaCl 실험군에 있어서의 돌연변이 빈도가 증가한 고조기간은 방사선 조사 후 6∼12일로 나타났으며 돌연변이 빈도는 방사선량 증가에 따라 선형적으로 증가하는 반응관계를 보였다. CT 실험군에서의 선량반응식 기울기(증가계수)는 5.99($r^2$=0.99)이었으나, NaCl+${\gamma}$실험군의 증가계수는 4.55($r^2$=0.98), ${\gamma}$+NaCl 실험군은 4.33($r^2$=0.99)으로 CT실험군의 값에 비해 낮았다. 즉, 방사선 조사 전후에 NaCl을 처리한 실험군들이 방사선만 조사한 CT 조사군에 비하여 방사선에 의한 돌연변이 유발증가율이 24% 이상 억제됨을 확인할 수 있었으며 이는 NaCl 자체가 방사선에 의한 DNA 손상에 대하여 방어효과를 갖기 때문인 것으로 해석될 수 있다.

• 대한핵의학회지
• /
• 제30권3호
• /
• pp.344-350
• /
• 1996

Iododeoxyuridine의 유사체인 Iodine-131-5-Iodo-2'-O-methyluridine을 합성하여 종양세포의 증식을 영상화하고자 하였다. 2'-O-methyluridine을 이용하여 Iodine-131-Iodomethyluridine을 요오드발생 반응(Iodogen reaction)으로 간편하게 합성하였고 이를 이용한 자가방사영상과 핵의학영상에서 종양세포의 증식을 영상화 할 수 있었다. 이상의 결과는 Iodine-131-Iodomethyluridine을 이용하여 종양세포의 증식을 감마카메라로 영상화하여 세포증식이 활발한 생존 종양조직이나 재발을 평가할 수 있는 가능성이 있음을 시사한다.

• 한국동물학회지
• /
• 제29권3호
• /
• pp.181-189
• /
• 1986

본 연구는 adenylate cyclase의 촉진제인 forskolin과 cholera toxin이 생쥐난자의 핵막붕괴 및 cAMP 합성에 미치는 영향을 조사하고자 수행되었다. 체외난자 배양방법과 adenylate cyclase assay 방법을 이용한 연구의 결과는 아래와 같다. 생쥐난자를 4시간 배양한 결과 대조군의 핵막붕괴율은 93%인데 반해서 forskolin (20-40$\\mu$g/ml)이 함유된 배양액에서 배양한 난자의 핵막붕괴율은 56-36%로써, forskolin의 농도에 비례하여 생쥐난자의 핵막붕괴가 현저하게 억제되었다. Forskolin (80 $\\mu$g/ml)을 3시간 처리한 후, 난자를 forskolin이 제거된 배양액으로 옮겼을 때 난자의 핵막붕괴율이 대조군과 비슷한 정도를 나타내고 있어 forskolin에 의한 핵막붕괴 억제현상은 가역적이었다. 한편, cholera toxin (10-1,000 ng/ml)은 생쥐난자의 핵막붕괴를 억제시키지 못했다. Forskolin (10-80 $\\mu$g/ml)을 생쥐난자 추출물에 첨가할 경우 cAMP합성이 5-18배 증가되었으나, cholera toxin (10-1,000 ng/ml)은 효과가 없었다. 덧붙여, adenylate cyclase의 regulatory unit의 촉진제인 guanidylimido-diphosphate (100$\\mu$M)를 forskolin과 함께 처리하여도 forskolin만 처리한 실험군에 비하여 cAMP합성정도에 변화가 없었다. 또한, cholera toxin과 guanidylimido-diphosphate(100$\\mu$M)를 함께 처리하여도 생쥐난자의 cAMP합성은 증가되지 않았다. 이상의 결과에서 forskolin에 의한 생쥐난자의 핵막붕괴 억제 현상은 난자내의 cAMP농도가 높아짐으로써 야기된 것이라 추측되며, 난자내의 cAMP 농도의 변화가 생쥐난자 성숙에 중요한 역할을 수행할 것이라고 사료된다.

• 한국임상약학회지
• /
• 제21권2호
• /
• pp.122-130
• /
• 2011

Objective: Although recombinant human erythropoietin (rhEPO) has revolutionized the treatment of anemia in chronic kidney disease (CKD) receiving hemodialysis (HD) with no need of blood transfusion, some patients have a blunted or appear to be resistant to rhEPO. There is a controversy in the causes of rhEPO resistance in maintenance HD patients with anemia. This study is to examine current anemia treatment outcomes and the factors influencing the rhEPO responsiveness in HD patient with CKD. Methods: The clinical parameters or factors relating to erythrompoietin treatment outcomes and erythropoietin responsiveness were collected from the HD patients in two large dialysis centers for three months. The collected paramenters included serum iron, total iron biding capacity (TIBC), transferrin saturation rate, ferritin, albumin, intact PTH, C-reactive protein (CRP), nPCR and medications such as an angiotensin converting enzyme inhbitor, an angiotension II receptor blocker and an HMG-CoA reductase inhibitor (HMG-CoA RI). The data were analyzed to examine the degree of acheiveing the anemia treatment goal and factors relating to ERI. Results: Among total 111 patients, 42 (42.3%) and 47 (37.8%) patients achieved the target Hct and Hb based on the Health Insurance Review and Assessment Services (HIRA) reimbursement criteria. In the higher ERI group (upper quartile), the patients had higher CRP levels (0.5 mg/dl) (p=0.0096), and lower TIBC score (<$240{\mu}g/dl$) (p=0.0027), and less patients were taking HMG-CoA RI (p=0.0019). Male patients (p=0.0204), patients with high TIBC score ($R^2$=0.084, p=0.0021) and patients taking HMG-CoA RI (p=0.0052) required to administer less dose of rhEPO meaning higher erythropoietin responsiveness. Conclusion: Less than 50% of CKD patients were achieving the goals of anemia by erythropoietin administration in large hospitals in Korea even though the goals were lower than those of NKF-K/DOQI practice guideline. The factors influencing ERI were sex, TIBC and HMG-CoA RI administration status, and neither an ACEI nor an ARB did not influence ERI.

• 한국환경성돌연변이발암원학회지
• /
• 제22권4호
• /
• pp.303-311
• /
• 2002

This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

• 한국식품영양과학회지
• /
• 제38권2호
• /
• pp.160-165
• /
• 2009

본 연구는 황금추출물인 baicalein의 피부알레르기 예방 효과를 알아본 연구로서 baicalein을 투여할 농도에 따라 0 mg/kg(대조군), 50 mg/kg(저용량군), 100 mg/kg(고용량군) 3개의 그룹으로 나누고, ear swelling을 측정하는 1군과 IgE 농도와 histamine 농도의 측정 및 조직병리학적 관찰을 위한 2군으로 나눠 실험을 하였다. Baicalein을 8일에 걸쳐 8회 경구투여를 실시한 후 접촉성 피부알레르기 유발 물질인 PCL을 귀에 감작시켜 알레르기를 유발시키고, 1군에서 ear swelling 변화를 확인하고 2군에서는 1군의 ear swelling의 결과에서 귀의 두께가 최고치를 이루는 시간대에 부검을 실시하여 적출한 조직으로는 HE염색과 TB염색을 실시하여 병변의 유무와 비만세포를 확인하였다. 채취한 혈청으로는 IgE 농도와 histamine 농도를 측정하였다. Ear swelling의 경우 0 mg/kg 농도의 baicalein을 투여한 대조군에 비해 50 mg/kg, 100 mg/kg 농도의 baicalein을 투여한 저용량군과 고용량군 그룹의 귀의 두께 증가폭이 낮게 나타났고, 저용량군보다 고용량군에서 그 증가폭이 낮게 나타났다. IgE 농도와 histamine 농도 측정결과에서도 0 mg/kg 농도의 baicalein을 투여한 대조군에 비해 50 mg/kg, 100 mg/kg 농도의 baicalein을 투여한 저용량군과 고용량군에서 낮은 수치가 나왔다. 조직병리학적 검사결과에서는 육안적으로 모든 그룹의 간과 신장에서는 별다른 병변은 관찰되지 않았고, HE염색을 한 귀 조직에서는 대조군에서 고용량군에 비해 귀의 두께가 두껍게 관찰되었고, TB염색을 한 귀 조직에서는 대조군에 비해 고용량군에서 적은 수의 비만세포들이 관찰되었다. 즉, ear swelling, IgE 농도, histamine 농도 및 조직병리학적 결과를 종합해봤을 때 황금추출물인 baicalein이 접촉성 피부알레르기 예방효과가 있다고 판단되어지고, 향후 baicalein은 항알레르기 치료제로 사용되는 생약제의 주요 성분으로 유용할 것이라 사료된다.

• 대한한의학방제학회지
• /
• 제21권2호
• /
• pp.144-157
• /
• 2013

Objectives : The aim of this study was to evaluate the efficacy of Hwangnyeonhaedok-tang (HH) and Geongangbuja-tang (GB) on the plasma hormone level in mice exposed to cold stress. HH and GB are the representative prescriptions of cold and hot property, respectively. Methods : We established cold condition by confining ICR mice to a $4^{\circ}C$ cage for 24 hours, ICR mice were given a HH (100, 300, 1000 mg/kg) or GB (100, 300, 1000 mg/kg) extract orally twice a day for three consecutive days. From the second day, they were given cold stress ($4^{\circ}C$) for twenty four hours. To measure the plasma corticosterone, insulin, thyroxine, epinephrine and norepinephrine levels of mice, their blood samples were collected from cardiac puncture, immediately centrifuged at $4^{\circ}C$. The protein level of HSP70 and JNK was examined using western blot analysis in cortex and hypothalamus. Results : Oral administration of GB more significantly reduced plasma corticosterone level raised by cold stress than HH. Gardeniae Fructus (CJ), the constituent of HH, significantly increased the thyroxine level. Western blot analysis showed that cold stress-induced Heat shock protein 70 (HSP70) expression was increased by HH and GB, HH decreased JNK expression and GB increased JNK expression dose-depently in hypothalamus. Scutellariae Radix (HG), Zingiberis Rhizoma (GG) and Aconiti Tuber (BJ) decreased HSP70 in hypothalamus and GG, BJ decreased HSP70 in cortex as well. Conclusions : These results suggest Geongangbuja-tang (GB) is more effective for ameliorating the stress response caused by cold stress.

• Clinical and Experimental Pediatrics
• /
• 제46권5호
• /
• pp.500-504
• /
• 2003

목 적: 소아의 가와사끼병에서 급성기 항염치료는 고용량의 IVIG와 경구용 아스피린의 병합투여가 일반적으로 사용되고 있다. 이러한 초기 항염치료에 반응을 보이지 않은 경우에는 IVIG의 추가투여나 스테로이드가 사용될 수 있으며 발열기간과 입원기간이 길어질 수 있다. 관련인자로서 환자의 나이, 성별, 발열-치료 간격과 백혈구수, CRP 등이 연관될 수 있다는 보고가 있었다. 저자들은 이러한 초기 치료실패에 임상적 또는 검사소견상의 관련인자가 있는가를 알아보기 위해 본 연구를 시행하였다. 방 법 : 1997년 6월부터 2002년 6월까지 만 5년간 원광대학교병원 소아과에서 가와사끼병으로 입원하여 치료받았던 177명의 환자를 대상으로 후향적으로 조사하였다. 1회의 투여로 반응을 보이지 않은 군(A군, n=19)과 반응을 보였던 대조군(B군, n=158)에서 나이와 성별, 발열에서 입원까지의 기간(hr)을 비교하였다. 입원 당시와 발병 6주째에 백혈구수와 혈소판, ESR, CRP, AST/ALT, ASO치, 소변검사, 관상동맥 심초음파 검사를 시행하여 비교하였다. 통계적 비교는 chi-square와 t-test를 이용하였다. 결 과 : 초기치료에 반응하지 않은 환아는 177례 중 19례(10.7%)였다. 나이와 성별, 백혈구수, 농뇨, 관상동맥의 이상에서는 두 군간에 유의한 차이가 없었다. 재치료군에서는 발열-입원 기간(hr)이 유의하게 짧았으며(P=0.041), AST/ALT치의 동반 상승(P=0.011), ASO치의 상승(P=0.000)이 관찰되었다. 결 론 : 백혈구수와 ESR, CRP의 증가나 AST, ALT가 따로 상승한 경우, 농뇨의 존재 여부에서는 재치료율과 관계가 없었다. 반면에, 발열-입원 기간이 짧았던 경우와 AST/ALT의 동시상승, ASO치 상승군에서 재치료율이 유의하게 높았다. 향후, AST/ALT치와 ASO치의 관련성에 대한 추가적인 연구가 더 필요할 것으로 사료된다.

• 한국대기환경학회지
• /
• 제2권1호
• /
• pp.11-21
• /
• 1986

The study was performed to investigate the effects of gaseous imission of sulfur dioxide and hydrogen fluoride on the growth of rice plant under stressed field conditions. The plants were cultivated in normal paddy fields where are 88 industrial plants operating with 285 smoke stacks emitting pollutants. There has been a number of reported studies (1, 3, 11, 19, 20) which deal with rice plant damages by air pollution under a simulated exposure experimental condition. Furthermore, these experiments were conducted to examine effects of a single pollutant on the plant. Furthermore, these experiments were conducted to examine effects of a single pollutant on the plant. In korea, however, there is no study reported in literature with respect to the in-situ dose-response relationship between rice pant reduction in yields and air pollution. This study is specifically dealt with multiple effects of sulfur dioxde and hydrogen fluoride on various plant growth indicators such as leaf damage, culm height, weight of grain, panicles per hill, spikelets per panicle and percent fertility.It appears that there is a good correlation between ambient concentrations of sulfur oxides and sulfur contents found in leaves with an average correlation coefficient of 0.868 within a 1% significance level. It is interesting to note that a better multiple correlation was found between percent leaf damage and sulfur and fluoride contentd found in leaf with a significance of 1% level. The yearly correlation coefficient ranges from 0.963 to 0.987 with an average being 0.971. It is, therefore, believed that a percent leaf damage may serve as a single indicator of pollutional damages to rice plant cultivating in fields. Regarding other factors to the diminution of rice plant growth in polluted atmosphere, it appears that a significant correlation to culm length and dry weight of grain with a 1% significance level whereas T/R ratio has a good correlation with lead damage within 5% significance level. An evaluation of data observed has demonstrated that both panicles per hill and percent fertility are significantly affected by air pollutants. As expected, hydrogen fluoride has more effects than sulfur oxide. It is, however, interesting to note that spikelets per panicles has slightly been affected while no indication of effects on 1000-grain-weight has been observed. This may lead to a conclusion that a reduction in yield of rice under polluted field conditions may have more been caused by the diminution of panicles per hill and percent fertility rather than by the diminution of spikelets per panicle and grain weight.