• 한국의학물리학회지:의학물리
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• 제21권1호
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• pp.35-41
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• 2010

본 연구는 생체 외 $^1H$ 고분해능 매직앵글스핀닝($^1H$ High-Resolution Magic Angle Spinning; $^1H$ HR MAS) 기술을 이용하여 정상군 adult mice의 뇌에서의 부위별 뇌 신경화학 대사물질(brain neurochemical metabolites)을 정량적으로 분석하고, 이를 이용하여 정상군의 뇌 대사물질의 표준 data base를 정립하기 위함이다. 실험에 사용된 adult mice는 C57BL/6J 모델의 체중 25~28 g, 40주령 수컷 10마리를 사용하였으며, 연령과 성별을 일치시켰다. 또한 뇌의 전두엽(frontal cortex), 측두엽(temporal cortex), 해마(hippocampus), 시상(thalamus) 총 4개의 부위를 채취하여 생체 외 $^1H$ 고분해능 매직앵글 스핀닝 실험을 진행 하였다. 생체 조직의 뇌 대사물질의 절대농도를 획득하기 위하여 대표적인 대사물질(Ace, NAA, NAAG, tCr, Cr, tCho, Cho, mIns, GPC+PC, Lac, GABA, Glu, Gln, tau, Ala)을 각 피크의 면적과 대사물질의 프로톤 개수를 계산하였다. 결과적으로 정상 군에서의 mice 뇌의 신경화학 대사물질들을 Acet, NAA, NAAG, Cho, mIns가 부위별로 절대농도차의 유의성을 나타내었으며, 이 외의 대사물질에서는 유의성이 없는 것으로 나타났다. 본 연구 결과를 토대로 $^1H$ HR-MAS을 이용한 생체조직 실험은 뇌조직 내 대사물질의 절대농도를 측정하고 기본적인 지표를 확보하는데 매우 정확하고 정량적인 방법이 될 수 있을 것으로 사료되며, 더 나아가 mice를 이용한 인간질병 모델의 실험동물에서의 뇌 신경화학 대사물질의 표준 자료화 하는데 도움이 될 수 있을 것으로 판단된다.

• 대한핵의학회지
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• 제38권6호
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• pp.528-531
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• 2004

목적: PET은 해상도 한계로 인하여 각종 소동물 실험에서 영상화하는데 현실적인 어려움이 많았다. 마이크로 PET의 등장으로 랫트나 마우스와 같은 실험 동물을 보다 나은 해상도로 평가할 수 있으나 실험 동물의 크기가 작기 때문에 영상이 사람에서와 같이 선명하지는 않다. 고양이와 같은 중소형 동물은 뇌가 상대적으로 크기 때문에 마이크로PET을 이용하여 보다 선명한 영상을 얻을 수 있다. 이 연구에서는 고양이 뇌 경색을 구축하고 마이크로PET으로 평가하였으며 시간에 따른 변화도 같이 평가하였다. 대상 및 방법 : 수컷 고양이 2마리를 사용하였으며, 체중은 각각 3.0 kg, 3.3 kg 이었다. Xylazine과 Ketamine HCl으로 마취하였다. 고양이 대천문에서 오른쪽으로 1cm되는 곳에 burr 구멍을 뚫은 후 30 G 바늘을 삽입하여 collagenase type IV 10 ${\mu}l$를 5분에 걸쳐 주사하여 뇌 경색 모델을 만들었다. 경색을 만든 후 1일, 11일, 32일 후에 마이크로 PET R4 scanner (Concorde Microsystems Inc., Knoxville, TN)을 사용하여 $^{18}F$-FDG PET 영상을 얻었다. 추가로 경색 13, 47일에 사람용 PET scanner (Gemini, Philips medical systems, CA, USA)를 사용하여 FDG-PET 촬영을 하였다. 결과: 성공적으로 고양이 뇌출혈경색 모델을 만들 수 있었으며 마이크로 PET으로 얻은 영상에서 병변의 당 대사는 시간이 지남에 따라서 호전되었다. 사람용 PET으로도 병변을 확인할 수 있었다. 결론: 고양이 2마리에 두개골을 통해 collagenase를 주입하여 성공적으로 출혈성 뇌 경색 모델을 만들었으며 $^{18}F$-FDG 마이크로 PET으로 영상화할 수 있었다.

• 한국의학물리학회:학술대회논문집
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• 한국의학물리학회 2003년도 제27회 추계학술대회
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• pp.74-74
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• 2003

Purpose: To investigate whether there are significant changes in regional brain metabolism in patients with Parkinson's disease after thalamotomy using proton magnetic resonance spectroscopy (lH MRS). Methods: Fifteen patients with Parkinson's disease of mean age 56.5 years (7 males and 8 females; mean age, 56.5 years) that have treated with levodopa were included. All patients with tremor experienced amelioration of their symptoms on the side contralateral to the thalamotomy. As a single-voxel technique, 1H MR spectra were obtained from the volume of interested regions in thalamus and primary motor cortex. Spectral parameters were: 20 ms TE, 2000 ms TR, 128 averages, 2500 Hz spectral width, and 2048 data points. Results: We found that NAA/Cho ratios showed generally low levels in thalamus in Parkinson's disease patients with clinical improvement following thalamotomy. Conclusions: 1H MRS may be a useful utility for the aid in better understanding the pathophy-siologic process in Parkinson's disease patients on the basis of the variation of NAA/Cho ratio. Acknowledgement: This study was supported by a grant of the Center for Functional and Metabolic Imaging Technology, Ministry of Health & Welfare, Republic of Korea (02-PJ3-PG6-EV07-0002).

• 환경생물
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• 제23권2호
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• pp.152-156
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• 2005

Ionizing radiation is a well- known therapy factor for human carcinoma cells. Genotoxic stress mediates cell cycle control, transcription and cellular signaling. In this work, we have used a microarray hybridization approach to characterize the cell type-specific transcriptional response of human carcinoma MCF-7 and HeLa cell line to $\gamma-radiation$, such as 4Gy 4hr. We found that exposure to $\gamma-ray$ alters by at least a $log_2$ factor of 1.0 the expression of known genes. Of the 27 genes affected by irradiation, 11 are down- regulated in MCF-7 cells and 2 genes induced by radiation,15 are repressed in HeLa cells. Many genes were involved in known damage- response pathways for cell cycling, transcription factor and cellular signaling response. However, in MCF-7 cells, we observed gene expression pattern in chromatin, apoptosis, stress, differentiation, cytokine, metabolism, ribosome and calcium. In HeLa cells, it showed clearly the expression changes in adhesion and migration, lysosome, brain, genome instability and translation. These insights reveal new therapy directions for studying the human carcinoma cell response to radiation.

• 한국축산식품학회지
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• 제34권1호
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• pp.65-72
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• 2014

This study is executed to develop probiotics which produce S-adenosyl-L-methionine (SAM), a methyl group donor of the 5-methyltetrahydrofolate methylation reaction within the animal cell. SAM is an essential substance for the synthesis, activation, and metabolism of hormones, neurotransmitters, nucleic acids, phospholipids, and cell membranes of animals. The SAM is also known as a nutritional supplement to improve brain functions of the human. In this study, the SAM-producing strains are identified in 18 types of salted fish, and then, the strains with excellent SAM productions are being identified, with 1 strain in the Enterococcus genus and 9 strains in the Bacillus genus. Strains with a large amount of SAM production include the lactic acid bacteria such as En. faecium and En. durans, En. sanguinicola, as well as various strains in the Bacillus genus. The SAM-overproducing strains show antibacterial activities with certain harmful microbes in addition to the weak acid resistances and strong bile resistances, indicating characteristics of probiotics. It is possible that the jeotgal-originated beneficial strains with overproducing SAM can be commercially utilized in order to manufacture SAM enriched foods.

• 생약학회지
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• 제30권2호
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• pp.145-150
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• 1999

To explain the theory of KIMI which is the theory of therapeutics in oriental medicine, monoamine oxidase(MAO) activities were measured in the brain and liver of mice which were orally administered oriental medicinal herbs which were classified into cold and hot drugs. Rheum palmatum, Anemarrhena asphodeloides, Gardenia jasminoides, Scutellaria baicalensis and Coptis japonica were considered as the cold drugs and Zingiber officinale, Aconitum carmichaeli, Asiasarum sieboldi, Evodia officinalis and Cinnamomum cassia were included in the hot drugs. The effects of cold and hot drugs on in vitro enzyme activities were measured and compared with the in vivo effects. Serotonin is important neurotransmetter involved in the control of body temperature. The MAO plays a central role in the metabolism of many neurotransmetter monoamines including serotonin. MAO is a flavoprotein found exclusively in the mitochondrial outer membrane, occuring in the MAO-A and MAO-B subtypes. MAO-A deaminates serotonin and noradrenaline, whereas MAO-B prefers phenylethylamine and benzylamine as substrates. Coptis japonica and Aconitum carmichaeli elevated the in vivo MAO activities and especialy, in vivo MAO-B activities were significantly increased. In vitro MAO-A activities were increased by hot drugs, whereas the in vitro MAO-B activities were inhibited. Cold drugs inhibited both enzyme activities in vitro.

• Journal of Pharmaceutical Investigation
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• 제29권1호
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• pp.47-53
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• 1999

Gastrodia elata (GE) is an oriental medicinal herb which has been used traditionally for the treatment of various brain diseases including convulsion and epilepsy. The purpose of this study was to determine pharmacokinetic parameters of 4-hydroxy-3-methoxybenzaldehyde (HMBA) and p-hydroxybenzaldehyde (PHBA), constituents of GE, in rats. Male rats were cannulated in the femoral vein, femoral artery, bile duct and ureter. They received a single i.v. bolus dose of either HMBA or PHBA through the femoral vein. The concentration of HMBA or PHBA in plasma, bile and urine samples were analyzed by reversed-phase HPLC. HMBA and PHBA have very short half-lives, i.e. 4.03 and 2.26 minutes respectively. Most of HMBA and PHBA were thought to be eliminated through metabolism as the metabolized fraction approaches unity. Derivatives of HMBA or PHBA with longer biological half-lives should be designed to develop better anticonvulsants and more complete qualitative and quantitative understanding of the overall pharmacokinetic fate of these compounds awaits further investigation.

• Clinical and Experimental Pediatrics
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• 제58권4호
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• pp.117-122
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• 2015

Global developmental delay (GDD) is a relatively common early-onset chronic neurological condition, which may have prenatal, perinatal, postnatal, or undetermined causes. Family history, physical and neurological examinations, and detailed history of environmental risk factors might suggest a specific disease. However, diagnostic laboratory tests, brain imaging, and other evidence-based evaluations are necessary in most cases to elucidate the causes. Diagnosis of GDD has recently improved because of remarkable advances in genetic technology, but this is an exhaustive and expensive evaluation that may not lead to therapeutic benefits in the majority of GDD patients. Inborn metabolic errors are one of the main targets for the treatment of GDD, although only a small proportion of GDD patients have this type of error. Nevertheless, diagnosis is often challenging because the phenotypes of many genetic or metabolic diseases often overlap, and their clinical spectra are much broader than currently known. Appropriate and cost-effective strategies including up-to-date information for the early identification of the "treatable" causes of GDD are needed for the development of well-timed therapeutic applications with the potential to improve neurodevelopmental outcomes.

• Reproductive and Developmental Biology
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• 제39권2호
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• pp.43-47
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• 2015

Sirtuin proteins are evolutionary conserved Sir2-related $NAD^+$-dependent deacetylases and regulate many of cellular processes such as metabolism, inflammation, transcription, and aging. Sirtuin contains activity of either ADP-ribosyltransferase or deacetyltranfease and their activity is dependent on the localization in cells. However, the expression pattern of Sirtuins has not been well studied. To examine the expression levels of Sirtuins, RT-PCR was performed using total RNAs from various tissues including liver, small intestine, heart, brain, kidney, lung, spleen, stomach, uterus, ovary, and testis. Sirtuins were highly expressed in most of tissues including the testis. Immunostaining assay showed that Sirt1 and Sirt6 were mainly located in the nucleus of germ cells, spermatocytes, and spermatids in the seminiferous tubules, whereas Sirt2 and Sirt5 were exclusively present in the cytoplasm of germ cells and spermatocytes. Our results indicate that Sirtuins may function as regulators of spermatogenesis and their activities might be dependent on their location in the seminiferous tubules.

• Journal of Applied Biological Chemistry
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• 제54권2호
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• pp.101-107
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• 2011

Aging in females is associated with a reduced metabolic function, increased incidence of neurodegenerative diseases, and cognitive dysfunction, as a result of loss in gonadal function. The change can alter the states of phosphorylation on the proteins, which cause dramatic changes in the cellular location or activity of the proteins. In this study, the differential phosphorylation of the proteins responsible for the functions related to cognition was studied using the ovariectomized adult rats. Phosphoproteomic analysis using the cerebral and hippocampal tissues could identify 51 differentially phosphorylated proteins including 12 proteins for energy metabolism, 8 cytoskeletal proteins, 6 signaling proteins, and other functional proteins in the ovariectomized rats. Further, anti-oxidative enzymes, superoxide dismutase and peroxiredoxin-2, which are known to be inactivated by phosphorylation, were found to be differentially phosphorylated in the cerebellum and hippocampus of the ovariectomized rats, respectively. Many of the deactivated proteins by differential phosphorylation identified in this study were overlapped to those of Alzheimer's disease cases. These results will provide information for neurodegenerative learning and memory impairments in women as brought about by menopause.