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Association of the G134A and G184C Polymorphisms in the CYP1A1 Gene with Lung Cancer Incidence

  • Ryu, Doug-Young;Huang, Ming-Ai;Park, Chang-Bo;Chang, Soo-Im;Im, Ruth;Choi, Seong-Jin;Kim, Na-Young;Park, In-Won;Choi, Byoung-Whui;Kim, Jae-Yeol;Shin, Jong-Wook;Choi, Jae-Chul;Choi, Byung-Sun;Park, Jung-Dock
    • Toxicological Research
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    • v.24 no.2
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    • pp.109-112
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    • 2008
  • The G184C and G134A single nucleotide polymorphisms(SNPs) of the CYP1A1 gene result in Ala62Pro and Gly45Asp substitutions, respectively. Here, we tested whether these SNPs are associated with an alteration in lung cancer incidence. We examined 80 Korean subjects with lung cancer and 240 age- and sex-matched controls. For each subject, the CYP1A1 gene was PCR amplified and sequenced. We observed that the odds ratio(OR) for lung cancer was 3.37 higher in subjects with the G184C polymorphism than in controls(95% confidence interval(CI), $0.89{\sim}12.73$, P=0.07). In contrast, the OR for lung cancer was 1.23 in subjects with the G134A polymorphism compared to controls(95% CI, $0.68{\sim}2.20$, P=0.49). The G184C polymorphism exacerbated the effects of smoking on lung cancer development. Gene-smoking interaction analyses revealed that past or present smokers with the G184C polymorphism had a higher incidence of lung cancer(OR, 24.72; 95% CI, $4.48{\sim}136.31$; P<0.01) than control smokers(OR, 6.65; 95% CI, $2.72{\sim}16.28$; P<0.01). However, there was only a slight difference in the ORs for lung cancer between control smokers and smokers with the G134A polymorphism. These findings suggest that the G184C polymorphism, but not the G134A polymorphism, is associated with an increased risk of lung cancer.

Efficient Diagnosis of Cucumber Green Mottle Mosaic Virus in Watermelon Using RT-PCR and Cloning of Coat Protein Gene (RT-PCR을 이용한 수박 Cucumber Green Mottle Mosaic Virus의 효율적인 진단 및 외피단백질 유전자의 클로닝)

  • 양덕춘;이진숙;김두욱;임용표;민병훈
    • Korean Journal of Plant Tissue Culture
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    • v.25 no.6
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    • pp.519-524
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    • 1998
  • A simple and reliable method to diagnose cucumber green mottle mosaic virus of watermelon in Korea (CGMMV-WK) was determined by RT-PCR, and coat protein gene for CGMMV-WK was cloned. Comparing to a method reported by Lee et al. (1996), the method developed here showed a better RT-PCR reaction. RT-PCR was possible by one step in the PCR reaction mixture that contains 20 pmol of primer, reverse transcriptase (30 unit), RNasin (5 unit) using the crude RNA solution. RT-PCR condition for specifically diagnosing CGMMV-WK was that cDNA was synthesized at 42$^{\circ}C$ for 45 min followed by pre-denaturation at 95$^{\circ}C$ for 2 min, and then PCR reaction was carried out with a programmed condition that consisted of 36 sequential cycles at 96$^{\circ}C$ for 30 sec, 6$0^{\circ}C$ for 30 sec, and 72$^{\circ}C$ for 1 min. A gene encoding the coat protein of CGMMV-WK was cloned and characterized. Nucleotide sequence of coat protein gene of CGMMV-WK shared 98.77% and 99.38% of sequence identity with those of CGMMV-W and CGMMV-SH, respecitvely, however, all of amino acid sequences were same.

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Dosimetry of $^{222}Rn$ Component in Outdoor Natural Background Radiation (자연 방사선량 중 $^{222}Rn$기여 성분 정량 해석)

  • Jun, Jae-Shik;Oh, Hi-Peel;Chae, Ha-Suk;Lee, Byung-Young;Kim, Do-Sung
    • Journal of Radiation Protection and Research
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    • v.14 no.2
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    • pp.10-17
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    • 1989
  • A study for the assessment of dose given by outdoor radon to respiratory system has been carried out by making use of radon-cups containing CR-39 plastic track detectors. Detection efficiencies were determined by irradiation of the radon-cups in a standard radon chamber of known concentration. Thus determined detection factors of CR-39 plastic track detector in bare, open cup and filtered cup geometry are found to be 0.273, 0.0813 and 0.0371 $trmm^{-2}$/(37$Bqm^{-3}{\cdot}d$), respectively, which are chemically etched in 30% NaOH solution of $70^{\circ}C$ for 220 minutes. The outdoor radon concentrations measured at Taejeon(Chungnam National University) from May 1988 to March 1989 are in the range of 27.4 - 135.8 Bq/$m^3$(0.74 - 3.67pCi/l)by open cup and 16.7 - 143.9 Bq/$m^3$(0.45 - 3.89 pCi/l) by filtered cup, which yield overall annual average value of outdoor radon concentration of $70.8Bq/m^3$(1.91 pCi/l). Corresponding effective dose equivalent rate to respiratory system of ICRP standard man is assessed to be 520 nSv /h.

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Metabolic Changes in Patients with Parkinson's Disease after Stereotactic Neurosurgery by Follow-up 1H MR Spectroscopy

  • Choe, Bo-Young;Baik, Hyun-Man;Chun, Shin-Soo;Son, Byung-Chul;Kim, Moon-Chan;Kim, Bum-Soo;Lee, Hyoung-Koo;Suh, Tae-Suk
    • Journal of the Korean Magnetic Resonance Society
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    • v.5 no.2
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    • pp.99-109
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    • 2001
  • Authors investigated neuronal changes of local cellular metabolism in the cerebral lesions of Parkinsonian symptomatic side between before and after stereotactic neurosurgery by follow-up 1H magnetic resonance spectroscopy (MRS). Patients with Parkinson's disease (PD) (n = 15) and age-matched normal controls (n = 15) underwen MRS examinations using a stimulated echo acquisition mode (STEAM) pulse sequence that provided 2${\times}$2${\times}$2 ㎤ (8ml) volume of interest in the regions of substantia nigra, thalamus, and lentiform nucleus. Spectral parameters were 20 ms TE, 2000 ms TR, 128 averages,2500 Hz spectral width, and 2048 data points. Raw data were processed by the SAGE data analysis package (GE Medical Systems). Peak areas of N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), inositols (Ins), and the sum (Glx) of glutamate and GABA were calculated by means of fitting the spectrum to a summation of Lorentzian curves using Marquardt algorithm. After blindly processed, we evaluated neuronal alterations of observable metabolite ratios between before and after stereotactic neurosurgery using Pearson product-moment analysis (SPSS, Ver. 6.0). A significant reduction of NAA/Cho ratio was observed in the cerebral lesion in substantia nigra of PD patient related to the symptomatic side after neurosurgery (P : 0.03). In thalamus, NAA/Cho ratio was also significantly decreased in the cerebral lesion including the electrode-surgical region (P : 0.03). A significant reduction of NAA/Cho ratio in lentiform nucleus was not oberved, but tended toward significant reduction after neurosurgery (P = 0.08). In particular, remarkable lactate signal was noted from the surgical thalamic lesions of 6 among 8 patients and internal segments of globus pallidus of 6 among 7 patients, respectively. Significant metabolic alterations of NAA/Cho ratio might reflect functional changes of neuropathological processes in the lesion of substantia nigra, thalamus, and lentiform nucleus, and could be a valuable finding fur evaluation of Parkinson's disease after neurosurgery. Increase of lactate signals, being remarkable in surgical lesions, could be consistent with a common consequence of neurosurgical necrosis. Thus, IH MRS could be a useful modality to evaluate the diagnostic and prognostic implications fur Parkinsons disease after functional neurosurgery.

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Combined MRI and Relaxogram: A New Method of Fat Study (MRI와 Relaxogram을 이용한 지질 연구의 새로운 기법에 관한 연구)

  • Yongmin Chang;Yoo, Done-Sik;Kim, Tae-Hun;Kim, Yong-Joo;Kang, Duk-Sik;Robert B. Clarkson
    • Progress in Medical Physics
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    • v.10 no.1
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    • pp.23-32
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    • 1999
  • Combined MRI and Relaxogram approach was introduced as a very useful tool for fat study. The phantoms simulating homogeneous mixture of fat and non-fat environments were measured with spin echo pulse sequence on a 0.15 T whole body imager. From 45 scans, the Tl values were obtained by fitting the data to continuous distribution (CONTIN) of relaxation time. This relaxogram gives broad distributions of relaxation time, which are characterized by a number of peaks with characteristic T1 values. Two distinct peaks in relaxogram were observed and identified as signals from com oil and gelatin gel. This model system can be served as simulating the distribution of fat in muscle. Also the relative ratio of two components, which is proportional to the area under the peak, is estimated and compared to nominal values. Based on the good agreement between two predictions, the values from our proposed method agreed with nominal values within $\pm$7 % error. The effects of different concentration of contrast agent and different region of interest are presented. To optimize total scan times, the minimum required data points and so further reduction in total scan times are discussed.

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Correction of Receiver Gain using Noise′s Standard Deviation for Reconstruction of T$_1$/T$_2$ Maps (T$_1$/T$_2$ maps 의 재구성을 위해 잡음의 표준편차를 이용한 수신 증폭률 보정)

  • 김미나;김성은;신승애;정은기
    • Progress in Medical Physics
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    • v.10 no.3
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    • pp.125-131
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    • 1999
  • T$_1$/T$_2$ weighted images are being used to give the characteristic contrast among the various tissues and the norma;/abnormal tissues. Abnormalities in tissues, in general, accompany the biochemical changes and eventually structural ones in which results in the change in T$_1$ and T$_2$ relaxation times of water protons. It has been suggested that the mapping of T$_1$/T$_2$ values may serve as a possible tool for the quantitative evaluation of the degree of abnormality. On reconstructing T$_1$/T$_2$ maps(or any other MR parametric map), only corresponding variables are to be varied, such as TE for T$_2$, TI or TR for T$_1$ and b-factor for diffusion images. But often the receiver gain is taken for the optimal usage of A/D converter, so that the set of the image data has different receiver gain. It must be corrected before any attempt to reconstruct the maps. Here we developed method of correcting receiver gain variation effect, using the standard deviation of noise on individual image. The resultant T$_1$ and T$_2$ values were very comparable to the other reported values.

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Turbo FLASH NRI Using Optimized Flip Angle Pattern: Application to Inversion-Recovery T1-Weighted Imaging (최적화된 Flip Angle Pattern을 사용한 Turbo FLASH MRI: Inversion-Recovery T1-Weighted Imaging에의 응용)

  • Oh, C.H.;Choi, H.J.;Yang, Y.J.;Lee, D.R.;Ryu, Y.C.;Hyun, J.H.;Kim, S.R.;Yi, Y.;Jung, K.J.;Ahn, C.B.
    • Proceedings of the KOSOMBE Conference
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    • v.1998 no.11
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    • pp.55-56
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    • 1998
  • The 3-D Fast Gradient Echo (Turbo FLASH, Turbo Fast Low Angle Shot) sequence is optimized to achieve a good T1 contrast using variable excitation flip angles. In Turbo FLASH sequence, depending on the contrast preparation scheme, various types of image contrast can be established. While proton density contrast is obtained when using a short repetition time with a short echo time and small flip angles, T1 or T2 weighting can be obtained with proper contrast preparation sequences applied before the above proton density Turbo FLASH sequence. To maximize the contrast to noise ratio while retaining a sharp impulse response (smooth frequency domain response), the excitation flip-angle pattern is optimized through simulation and experiments. The TI (the delay after the preparation sequence which is a 180 degree inversion RF pulse in the IR T1 weighted imaging case), TD (the delay time between the Turbo FLASH sequence and the next preparation), and TR are also optimized fur the best image quality. The proposed 3-D Turbo FLASH provides $1mm\times1mm\times1.5mm$ high resolution images within a reasonable 5-8 minutes of imaging time. The proposed imaging sequence has been implemented in a Medison's Magnum 1.0T system and verified through simulations as well as human volunteer imaging. The experimental results show the utility of the proposed method.

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Molecular Mechanism of Tetrabromobisphenol A (TBBPA)-induced Target Organ Toxicity in Sprague-Dawley Male Rats

  • Choi, Jae-Seok;Lee, Young-Jun;Kim, Tae-Hyung;Lim, Hyun-Jung;Ahn, Mee-Young;Kwack, Seung-Jun;Kang, Tae-Seok;Park, Kui-Lea;Lee, Jae-Won;Kim, Nam-Deuk;Jeong, Tae-Cheon;Kim, Sang-Geum;Jeong, Hye-Gwang;Lee, Byung-Mu;Kim, Hyung-Sik
    • Toxicological Research
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    • v.27 no.2
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    • pp.61-70
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    • 2011
  • Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.

Effects of Diglyceride-Conjugated Linoleic Acid on Proliferation and Differentiation of 3T3-L1 Cells

  • Jeong, Jae-Hwang;Lee, Sang-Hwa;Hue, Jin-Joo;Lee, Yea-Eun;Lee, Young-Ho;Hong, Soon-Ki;Jeong, Seong-Woon;Nam, Sang-Yoon;Yun, Young-Won;Lee, Beom-Jun
    • Toxicological Research
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    • v.23 no.3
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    • pp.223-229
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    • 2007
  • Conjugated linoleic acid (CLA) has been recently reported to have an anti-obesity effect in animals and humans. The objective of this study was to investigate effects of diglyceride (DG)-CLA on proliferation and differentiation of 3T3-L1 preadipocytes. Cell proliferation was determined using WST-8 analysis and cell differentiation was determined by glycerol-3-phosphate dehydrogenase (GPDH) activity. Lipid accumulation in differentiating 3T3-L1 cells was determined by Oil red O staining. There were four experimental groups including vehicle control (DMSO), CLA, triglyceride (TG)-CLA, and DG-CLA. Treatments of CLA, TG-CLA, and DG-CLA at the concentrations of $10{\sim}1000{\mu}g/ml$ reduced proliferation of preconfluent 3T3-L1 cells in a dose-dependent manner. Among them CLA was the most effective in the proliferation inhibition of preconfluent 3T3-L1 cells with increasing concentrations. Treatments of CLA and DG-CLA at the concentration of $100{\mu}g/ml$ significantly inhibited differentiation of postconfluent 3T3-L1 cells as measured by GPOH activity (p<0.05). In addition, treatments of CLA, TG-CLA, and DG-CLA effectively inhibited lipid accumulation during differentiation of 3T3-L 1 cells. OG-CLA had the most inhibitory effect on the differentiation and lipid accumulation. These results suggest that the compounds including CLA have a respectable anti-obesity effect and that consumption of DG-CLA as a dietary oil may give a benefit for controlling overweight in humans.

The Effect of Systemic Iron Level on the Transport and Distribution of Copper to the Brain (체내 철 수준이 뇌로의 구리 이동과 분포에 미치는 영향)

  • Choi, Jae-Hyuck;Park, Jung-Duck;Choi, Byung-Sun
    • Toxicological Research
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    • v.23 no.3
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    • pp.279-287
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    • 2007
  • Copper (Cu) is an essential trace element indispensable for brain development and function; either excess or deficiency in Cu can cause brain malfunction. While it is known that Cu and Fe homeostasis are strictly regulated in the brain, the question as to how systemic Fe status may influence brain Cu distribution was poorly understood. This study was designed to test the hypothesis that dietary Fe condition affects Cu transport into the brain, leading to an altered brain distribution of Cu. Rats were divided into 3 groups; an Fe-deficient (Fe-D) group which received an Fe-D diet ($3{\sim}5 mg$ Fe/kg), a control group that was fed with normal diet (35mg Fe/kg), and an Fe-overload group whose diet contained an Fe-O diet (20g carbonyl Fe/kg). Following a 4-week treatment, the concentration of Cu/Fe in serum, CSF (cerebrospinal fluid) and brain were determined by AAS, and the uptake rates of Cu into choroids plexus (CP), CSF, brain capillary and parenchyma were determined by an in situ brain perfusion, followed by capillary depletion. In Fe-D and Fe-O, serum Fe level decreased by 91% (p<0.01) and increased by 131% (p<0.01), respectively, in comparison to controls. Fe concentrations in all brain regions tested (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were lower than those of controls in Fe-D rats (p<0.05), but not changed in Fe-O rats. In Fe-D animals, serum and CSF Cu were not affected, while brain Cu levels in all tested regions (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were significantly increased (p<0.05). Likewise, the unidirectional transport rate constants $(K_{in})$ of Cu in CP, CSF, brain capillary and parenchyma were significantly increased (p<0.05) in the Fe-D rats. In contrast, with Fe-O, serum, CSF and brain Cu concentrations were significantly decreased as compared to controls (p<0.05). Cu transport was no significant change of Cu transport of serum in Fe-O rats. The mRNA levels of five Cu-related transporters were not affected by Fe status except DMT1 in the CP, which was increased in Fe-D and decreased in Fe-O. Our data suggest that Cu transport into brain and ensuing brain Cu levels are regulated by systemic Fe status. Fe deficiency appears to augment Cu transport by brain barriers, leading to an accumulation of Cu in brain parenchyma.