• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.321-323
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• 2003

Hyoscyamine and scopolamine are the pharmaceutically valuable anticholinergic drugs. The aim of our study is to increase the contents of both hyoscyamine and scopolamine by means of elicitation. Various biotic elicitors derived from 3 fungi and 1 yeast were inoculated to the hairy root cultures. When homogenate and supernatant of elicitors treated with hairy root cultures, that of yeast elicitor was only increased scopolamine production. However, all of the fungal elicitors did not influenced the productions of scopolamine and hyoscyamine. Our results will contribute to mass production of tropane alkaloids by hairy root cultures of Scopolia parviflora.

• Korean Journal of Medicinal Crop Science
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• v.12 no.5
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• pp.378-383
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• 2004

Scopolamine and hyoscyamine are important anticholinergic compounds. To increase the productivity, we have selected various elicitors and developed culture system using a bubble column bioreactor (BCB). As the same manner of elicitation in flask cultures, the elicitors were introduced into BCB cultures and the productivity was investigated. Except the bacterial elicitor of Staphyllococcus aureus, the elicitors inhibited hyoscyamine production. In scopolamine production, the elicitors revealed different responses from the results obtained in flask cultures. The elicitors of KCl and Candida albicans less increased the production than flask cultures. However, methyl jasmonate and S. aureus showed stronger positive effects on tropane alkaloid production. In particular, S. aureus was the most effective elicitor on scopolamine production and the elicitor resulted in the highly increased production, approximately 10 times higher than the control culture.

• Genomics & Informatics
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• v.20 no.4
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• pp.43.1-43.18
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• 2022

Atropa belladonna is a valuable medicinal plant and a commercial source of tropane alkaloids, which are frequently utilized in therapeutic practice. In this study, bioinformatic methodologies were used to examine the pattern of coding sequences and the factors that might influence codon usage bias in the chloroplast genome of Atropa belladonna and other nightshade genomes. The chloroplast engineering being a promising field in modern biotechnology, the characterization of chloroplast genome is very important. The results revealed that the chloroplast genomes of Nicotiana tabacum, Solanum lycopersicum, Capsicum frutescens, Datura stramonium, Lyciumbarbarum, Solanum melongena, and Solanum tuberosum exhibited comparable codon usage patterns. In these chloroplast genomes, we observed a weak codon usage bias. According to the correspondence analysis, the genesis of the codon use bias in these chloroplast genes might be explained by natural selection, directed mutational pressure, and other factors. GC12 and GC3S were shown to have no meaningful relationship. Further research revealed that natural selection primarily shaped the codon usage in A. belladonna and other nightshade genomes for translational efficiency. The sequencing properties of these chloroplast genomes were also investigated by investing the occurrences of palindromes and inverted repeats, which would be useful for future research on medicinal plants.

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.568-570
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• 2003

The Hyoscyamus niger hyoscyamine $6{\beta}-hydroxylase$ (H6H, EC 1.14.11.11) gene was introduced into the genome of a Scopolia parviflora by the binary vector system using the disarmed Agrobacterium rhizogenes strain KCTC 2703. Expression of H6H enzyme which are involved in alkaloids pathway by western blot analysis using proteins extracted from leaf, stem flower, branch root and main root were examined The enzyme expression was found only in the roots, with no expression in leaf, stem and flower. The alkaloids contents were the most higher in root and then leaf and stem has very small amount of alkaloid contents were analyzed by HPLC. The expression level of H6H in transgenic plants were two or more times than wild type plants. In transgenic plant which constitutively expresses H6H enzyme, high concentration of scopolamine was accumulated.

• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.342-348
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• 2001

Objective : Dopamine transporter concentrations have been known to decrease in Parkinson's disease(PD). The aim of the present study was to evaluate the correlation between SPECT measurements of [I-123]N-(3-iodopropene-2-yl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-chlorophenyl) tropane(IPT) as an imaging agent for measuring changes in transporter concentrations with PD. Patients and Methods : IPT labelled with $4.87{\pm}1.29mCi$($180.19{\pm}47.73MBq$) of [I-123] was intravenously injected into 23 patients(age : $58{\pm}12$) with PD and three normal controls(NC)(age : $37{\pm}7$) as bolus. Brain SPECT were then performed at 1 hour and 2 hours after injection on a double headed camera. The statistical parameters were the contrast ratio of left basal ganglia(BG) and right basal ganglia to occipital cortex(OCC) per milli curies of injected radiotracer at 1 hour and 2 hours. The correlations were evaluated between these parameters and Hoehn-Yahr classification of the patients. Results : The(BG - OCC)/OCC/mCi ratios at 1 hour and 2 hours for PD and NC were $0.14{\pm}0.07$ and $0.27{\pm}0.07$(1 hour) and $0.12{\pm}0.07$ and $0.34{\pm}0.04$(2 hour), respectively. The(BG - OCC)/OCC/mCi ratios of Parkinson's disease were decreased with higher grade of Hoehn-Yahr classification of the patients. The ratio between BG and OCC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. Conclusion : The findings suggest that IPT may be a very useful tracer for early diagnosis and treatment of PD and study of dopamine re-uptake site.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.19-34
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• 1996

[ $[^{123}I]{\beta}$ ]-CIT [$2{\beta}$-carbomethoxy-$3{\beta}$-(4-iodophenyl)tropane]는 도파민 운반체 (dopamine transporter)에 특이결합하며 $[^{123}I]{\beta}$-CIT의 도파민 운반체 결합정도는 파킨슨병에서 도파민 뉴우런의 변성정도를 반영하는 것으로 제안되어 왔다. 이 연구의 주요 목적은 파킨슨병 환자에서 $[^{123}I]{\beta}$-CIT SPECT를 이용하여 측정된 $[^{123}I]{\beta}$-CIT의 선조체 결합지표들이 질병의 임상적 진행정도를 반영하는지를 검토하고, 간편화된 조직방사능비가 $[^{123}I]{\beta}$-CIT의 결합정도를 나타내는 정량적 지표로 이용될 수 있는지를 검증하는 것이었다. 파킨슨병 환자 30명($59{\pm}9$세, 평균${\pm}$표준편차: Hoehn-Yahr stage 1-3)과 정상인 6명 ($58{\pm}5$세)을 대상으로 $[^{123}I]{\beta}$-CIT SPECT 영상을 얻었다. $[^{123}I]{\beta}$-CIT 선조체 결합의 정량적 지표로서 (선조체 방사능-소뇌방사능)/소뇌방사능 비(specific binding ratio, SBR)와 추적자역학모델을 이용하여 측정한 선조체 결합능(binding potential)($k_3/k_4$)을 구하였다. 파킨슨병 환자에서 $[^{123}I]{\beta}$-CIT의 선조체 결합역학은 정상인에 비하여 현저하게 느렸으며 그 결합지표들은 정상인에 비하여 뚜렷하게 낮았다. 한편, 편측파킨슨병 환자에서 $[^{123}I]{\beta}$-CIT 결합은 증상 반대쪽 선조체 뿐만 아니라 같은 쪽 선조체에서도 정상인에 비해 유의하게 감소되어 있었다. 파킨슨병 환자에서 $[^{123}I]{\beta}$-CIT 투여 후 24시간의 선조체 SBR 및 최대 SBR, 선조체 결합능은 모두, 유병기간, Hoehn-Yahr stage, UPDRS(Unified Parkinson's Disease Rating Scale) 총점, UPDRS 운동점수, UPDRS 일상활동점수와 유의한 상관관계를 나타내었다. 24시간 선조체 SBR과 최대 SBR은 선조체 결합능과 우수한 상관관계를 보였다. 이상의 결과로부터 $[^{123}I]{\beta}$-CIT의 선조체 결합은 파킨슨병의 진행정도를 나타내는 지표로 이용될 수 있다. 또 $[^{123}I]{\beta}$-CIT 투여 후 24시간 영상으로부터 얻은 간편화된 조직방사능 비는 $[^{123}I]{\beta}$-CIT의 결합정도를 정량적으로 반영한다. $[^{123}I]{\beta}$-CIT SPECT는 파킨슨병의 조기진단 및 진행 추적에 임상적으로 유용할 것으로 판단된다.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.35-46
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• 1996

Dopamine transporter concentrations have been known to decrease in Parkinson's disease (PD) or increase in Tourette's disorder. The purpose of this study was to evaluate the effectiveness of [I-123]N-(3-iodopropene-2-yl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-chlorophenyl) tropane (IPT) as an imaging agent for measuring changes in transporter concentrations with PD. IPT labelled with 6.69+/-0.64 mCi(247.53+/-23.68 MBq) of I-123 was intravenously injected into ten patients(age: 55+/-11) with PD, and six normal controls(NC)(age: 46+/-14) as a bolus. Dynamic SPECT scans of the brain were then performed for 5 minutes each over 120 minutes on a triple headed camera. Time activity curves were generated for the left basal ganglia(LBG), right basal ganglia(RBC), and occipital cortex(OCC). The statistical parameters included the time to peak activity, the contrast ratio of LBG and RBG to OCC at several time points, and the accumulated specific binding counts/mCi/pixel(ASBC) from 0 to 115 minutes. The uptake of IPT in the brains of PD and NC peaked within 10 minutes of injection in all subjects. The maximum target to background ratio in the basal ganglia of PD and NC occurred at 85+/-20 min and 110+/-6 min of injection, respectively. The BG/OCC ratios at 115 minutes for PD and NC were 2.15+/-0.54 and 4.26+/-0.73, respectively. The ASBC at 115 minutes for PD and NC were 152.91+/-50.09 and 289.51+/-49.00, respectively. The ratio of BG/OCC for the NC was significantly higher than the ratio for PD. SPECT data matched with clinical diagnosis for PDs. The ratio between BG and OCC and the ASBC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. The findings suggest that IPT may be a very useful tracer for early diagnosis of PD and study of dopamine reuptake site.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.41-51
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• 2004

PURPOSE: Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled $N-(3-iodopropen-2-yl)-2{\beta}-carbomethoxy-3beta-(4-chlorophenyl)tropane$ ($[^{123}I]IPT$) single photon omission computed tomography (SPECT). MATERIALS and METHODS: $[^{123}I]IPT$ SPECT Imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of $[^{123}I]IPT$. RESULTS: Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. CONCLUSION: These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.

• The Korean Journal of Nuclear Medicine
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• v.37 no.4
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• pp.235-244
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• 2003

Purpose: Attention deficit hyperactivity disorder (ADHD) has been known as psychiatric disorder in childhood associated with dopamine dysregulation. In present study, we investigated changes in dopamine transporter (DAT) density of the basal ganglias using I-123 N-(3-iodopropen-2-yl) -2-carbomethoxy-3beta-(4-chlorophenyl) tropane [I-123 IPT] SPECT in children with ADHD before and after methylphenidate treatment. Materials and Method: Nine drug-naive children with ADHD and seven normal children were included in the study. We peformed brain SPECT two hours after the intravenous administration of I-123 IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of soecific/nonspecific DAT binding ratios in the basal ganglia. All children with ADHD reperformed [123I]IPT SPECT after treatment with methylphenidate(0.7mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/nonspecific DAT binding ratio of basal ganglia. Results: Children with ADHD had a significantly greater specificinonspecific DAT binding ratio of the basal ganglia comparing to normal children(Right : z = 2.057, p = 0.041 : Left : z : 2.096, p = 0.032). Under treatment with methylphenidate in all children with ADHD, specificinonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right : t = 3.239, p = 0.018 ; Left : t = 3.133, p = 0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. Conclusions: These findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.