• Molecules and Cells
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• 제42권6호
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• pp.480-494
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• 2019

Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.

• Journal of Radiation Protection and Research
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• 제12권2호
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• pp.9-18
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• 1987

천연 우라늄의 주독성이 중금속독성인지 혹은 방사성장해독성인지를 알기 위하여 질산납과 질산우라늄을 투여하여 변동되는 혈중 BUN, Creatinine, C-AMP 및 $PGE_2$의 활성도를 측정 비교하였다. 질산우라늄 투여시 비호소계인 질산대사의 임상적 지표인 BUN 및 Creatinine값은 질산납 투여군에 비교하여 예민한 반응을 나타났으나 C-AMP의 활성도에는 의의있는 변화가 없었다. 한편 질산 우라늄의 농도 변화에 따른 $PGE_2$ 활성도의 변동은 질산납 투여와 달리 현저하게 증가 되는 것을 관찰하였다. 이 결과는 천연우라늄의 저준위 방출 방사선이 세포막에 반응하여 $PGE_2$농도에 변화를 주는 것으로 사료된다. 질산 우라늄의 투여로 증가된 혈중 $PGE_2$의 농도를 감퇴시킴에 있어 Glucagon, Aldosterone 및 Furosemide를 사용하였다.

• 대한수의학회지
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• 제25권2호
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• pp.187-195
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• 1985

The Present study has been carried out to elucidate the antiestrogenic effects of tamoxifen in uteri of immature rats. Immature female Sprague-Dawley rats were allocated into 4, groups and injected with $5{\mu}g$ of estradiol-$17{\beta}$, $50{\mu}g$ of tamoxifen, a combination of both or vehicle only subcutaneously three times after an interval of 24 hours respectively. The concentrations, of cytosol estradiol receptor in uterus were measured by DCC method before and 1, 3, 6, 12, 24, 48 and 72 hours after the above treatments and those of nuclear estradiol were measured by protamine exchange method 72 hours and those of nuclear estradiol were measured by protamine exchange method 72 hours after the above treatments. The results obtained were summarized as follows: 1. The binding affinity of tamoxifen to estradiol receptor in uterine cytosol was lower than that of estradiol-$17{\beta}$, accordingly the translocation of estradiol receptor into the nucleus was found to be delayed. 2. Tamoxifen caused the retention of estradiol receptor in nucleus over 24 hours and inhibited the replenishment of the receptor from nucleus to cytosol in uterus.

• 핵의학기술
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• 제27권2호
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• pp.129-132
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• 2023

Purpose: Positron emisson tomography (PET) is a crucial medical imaging scanner for the detection of cancer lesions. In order to maintain the improved image quality, it is crucial to apply detectors of superior performance. Therefore, the purpose of this study was to compare PET image quality using Monte Carlo simulation based on the detector materials of BGO, LSO, and LuAP. Materials and Methods: The Geant4 Application for Tomographic Emission (GATE) was used to design the PET detector. Scintillations with BGO, LSO and LuAP were modelled, with a size of 3.95 × 5.3 mm2 (width × height) and 25.0 mm (thickness). The PET detector consisted of 34 blocks per ring and a total of 4 rings. A line source of 1 MBq was modelled and acquired with a radius of 1 mm and length of 20 mm for 20 seconds. The acquired image was reconstructed maximum likelihood expectation maximization with 2 iteration and 10 subsets. The count comparison was carried out. Results and Discussion: The highest true, random, and scatter counts were obtained from the BGO scintillation detector compared to LSO and LuAP. Conclusion: The BGO scintillation detector material indicated excellent performance in terms of detection of gamma rays from emitted PET phantom.

• 대한핵의학회지
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• 제26권2호
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• pp.257-264
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• 1992

Diagnostic approaches such as angiography, ultrasound, computed tomography and nuclear magnetic resonance have limitation for contributing to the early clinical diagnosis of atherosclerosis. Recently, $^{99m}Tc-labelled$ low density lipoprotein was developed to detect early atherosclerotic lesion by external imaging with gamma camera. To determine whether $^{99m}Tc-LDL$ scintigraphy can visualize the active atherosclerotic lesion, rabbits were injected with $^{99m}Tc-LDL$, 3 months after feeding dietary fat (lanolin) and we obtained following results. 1) Labelling efficiency of $^{99m}Tc-LDL$ was $79\sim88%$. 2) Biodistribution study of normal rabbits with $^{99m}Tc-LDL$ revealed the high activities in spleen, adrenal gland, liver, kidney which are major organs of high metabolic rate of LDL. 3) Three months after feeding lanolin, serum cholesterol was markedly increased from $74{\pm}17mg/dl$ to $979{\pm}153mg/dl$ and histologic study of aorta after sacrificing the rabbit demonstrated marked atherosclerotic changes. 4) Atherosclerotic lesion of abdominal aorta which was confirmed with histologic study could be demonstrated in $^{99m}Tc-LDL$ scintigraphy after feeding lanolin for 3 months. In conclusion, the results of this preliminary investigation suggest that it may be possible to image active atheromatous lesion with $^{99m}Tc-LDL$. It is anticipated that this promising agent may allow the in vivo monitoring of preclinical atherosclerotic lesions and may be useful to evaluate the metabolic pathway of LDL in humans.

• Nuclear Medicine and Molecular Imaging
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• 제41권4호
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• pp.317-325
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• 2007

동적 PET 데이터는 구획모델과 Nonlinear Least Squares(NLS)방법을 사용하여 분석함으로서 각종 생화학적 물질의 생체 대사율 등을 정량화 할 수 있다. 하지만 NLS방법은 변수의 초기 값이 적절하지 않을 경우 지역적인 최소점에 빠지거나 계산시간이 길어 동역학 변수들을 각 화소마다 구해야 하는 파라메터 영상(parametric image) 구성에는 효과적이지 않다. Patlak 도표분석법(PGA)은 비선형 방정식을 선형화하여 값을 추정함으로서 간단하면서 적은 계산량으로 인해 파라메터 영상을 구성하는데 많이 사용되고 있으나 잡음성분과 선형구간 선정에 따라 값이 영향을 받는 단점이 있다. 따라서 이 연구에서는 3구획 비가역 모델에 적합한 다중선형분석법(MLAIR)을 고안하였으며 3구획 비가역 모델의 대표적 예인 $[^{18}F]Fluoride$ PET을 이용하여 미니돼지에서의 뼈 섭취률을 계산하여 PGA방법과 비교 분석해 보았다. 대상 및 방법: 3마리의 미니돼지를 대상으로 100MBq의 $[^{18}F]Fluoride$를 대퇴부 정맥에 주사하면서 ECAT EXAET 47 PET 스캐너를 이용하여 60분간 PET 영상을 얻었다. 케타민과 자일라진을 이용하여 30분 간격으로 마취하였으며 실험동물을 진공 쿠션을 이용하여 반드시 누운 자세로 위치하도록 고정 시켰다. 입력함수인 혈장 내 농도곡선은 대퇴동맥으로부터 스캔 시작과 함께 혈액 채취를 통해 얻었다. ROI분석을 위해 대퇴골두, 척추 뼈, 근육에 ROI를 그려 조직 내 시간-방사능 곡선을 얻었다. $k_4$가 0인 3구획 비가역 모델로부터 MLAIR와 PGA방법을 사용하여 관심영역에서의 뼈 섭취률 $K_i$와 파라메터 영상을 구성하였다. PGA방법은 선형구간의 시작점인 $t^*$선택에 따른 영향을 보기 위해 분석구간을 변화시켜가며 분석하였다. 결과: ROI 분석결과 추정된 $K_i$값은 NLS방법에 비하여 MLAIR방법과 PGA방법 모두에서 과대 추정되었으나 두 분석방법 끼리는 비슷한결과를 보였다. Patlak 기울기는 $t^*$선택에 따라 값이 변하였으며 Patlak 상수는 Fluoride 섭취가 높은 대퇴골두나 척추뼈에서 30분이 지나서야 일정한 값으로 나타났고 섭취가 낮은 근육에서는 10분만에 일정해졌다. 파라메터 영상에서는 제안한 MLAIR방법이 PGA방법에 비해 영상의 질을 향상시킴을 알 수 있었다. 또한 PGA방법을 이용하여 구성한 파라메터 영상은 $t^*$값이 커질수록 급격히 영상의 질이 저하됨을 볼 수 있다. 특히 Fluoride 섭취가 높은 영역에서 Patlak 상수가 일정해지는 시간인 $t^*$값이 30분일 때 파라메터 영상은 MLAIR와 크게 차이가 났다. 결론 결론적으로 제안한 MLAIR방법은 선형구간을 정할 필요 없이 모든 데이터를 사용하는 이점이 있으며 선형적인 방법을 통해 $K_i$값을 얻을 수 있어 계산시간을 단축 시켜 줄 뿐 아니라 잡음성분에 강해 파라메터 영상의 질을 크게 향상 시켜 줌으로 비가역 3구획모델에서의 PGA방법을 대체할 새로운 파라메터 영상구성방법으로 적합할 것이다.

• Reproductive and Developmental Biology
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• 제32권2호
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• pp.135-140
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• 2008

Recent studies on nuclear transfer and induced pluripotent stem cells have demonstrated that differentiated somatic cells can be returned to the undifferentiated state by reversing their developmental process. These epigenetically reprogrammed somatic cells may again be differentiated into various cell types, and used for cell replacement therapies through autologous transplantation to treat many degenerative diseases. To date, however, reprogramming of somatic cells into undifferentiated cells has been extremely inefficient. Hence, reliable markers to identify the event of reprogramming would assist effective selection of reprogrammed cells. In this study, a transgene construct encoding enhanced green fluorescent protein (EGFP) under the regulation of human Oct4 promoter was developed as a reporter for the reprogramming of somatic cells. Microinjection of the transgene construct into pronuclei of fertilized mouse eggs resulted in the emission of green fluorescence, suggesting that the undifferentiated cytoplasmic environment provided by fertilized eggs induces the expression of EGFP. Next, the transgene construct was introduced into human embryonic fibroblasts, and the nuclei from these cells were transferred into enucleated porcine oocytes. Along with their in vitro development, nuclear transfer embryos emitted green fluorescence, suggesting the reprogramming of donor nuclei in nuclear transfer embryos. The results of the present study demonstrate that expression of the transgene under the regulation of human Oct4 promoter coincides with epigenetic reprogramming, and may be used as a convenient marker that non-invasively reflects reprogramming of somatic cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1019-1024
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• 2015

Background: Survival of breast cancer patients depends on a number of factors which are not only prognostic but are also predictive. A number of studies have been carried out worldwide to find out prognostic and predictive significance of different clinicopathological and molecular variables in breast cancer. This study was carried out at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad, to find out the impact of different factors on overall survival of breast cancer patients coming from Northern Pakistan. Materials and Methods: This observational retrospective study was carried out in the Oncology Department of NORI Hospital. A total of 2,666 patients were included. Data were entered into SPSS 20. Multinomial logistic regression analysis was performed to determine associations of different variables with overall survival. P values <0.05 were considered significant. Results: The mean age of the patients was 47.6 years, 49.5% being postmenopausal. Some 1,708 were ER positive and 1,615 were PR positive, while Her 2 neu oncogene positivity was found in 683. A total of 1,237 presented with skin involvement and 426 had chest wall involvement. Some 1,663 had > 5cm tumors. Lymph node involvement was detected in 2,131. Overall survival was less than 5 years in 669 patients, only 324 surviving for more than 10 years, and in the remainder overall survival was in the range of 5-10 years. Conclusions: Tumor size, lymph node metastases, receptor status, her 2 neu positivity, skin involvement, and chest wall involvement have significant effects whereas age and menopausal status have no significant effect on overall survival of breast cancer patients in Pakistan.

• 대한핵의학회지
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• 제26권2호
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• pp.235-243
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• 1992

Patterns of abnormality in regional cerebral perfusion and its relation to clinical severity was evaluated with 32 head injury patients using $^{99m}Tc-HMPAO$ single photon emission tomography (SPECT). The findings were compared with computed tomography (CT) done within 48 hours of each SPECT study. The initial SPECT study was done within 7 days of injury in 16 cases, between 1 week and 2 months in 12, and after over 2 months in 4. Nineteen of the patients underwent followup SPECT and CT after a mean interval of 1 to 2 months. The initial SPECT showed abnormalities in 96% (31/32) of the patients while CT showed abnormal findings in only 81% (26/32). There were a total of 54 supratentorial SPECT lesions in all. Ninity percent (49/54) of these were of regional hypoperfusion, while 5 lesions showed focal hyperperfusion. The lesions were most often localized in the frontal and temporal lobes. Fifty five percent (30/54) were areas not detected as a lesion on CT. Cerebellar diaschisis was observed in 50% (16/32) of the patients. The degree of perfusion abnormality was quantified by the product of differential activity and a size factor. Correlation between the degree of perfusion abnormality and the clinical severity (Glasgow coma scale) failed to show statistical significance (p=0.053). The amount of change in the degree of perfusion abnormality on follow up SPECT was compared to the amount of change in clinical severity. Perfusion abnormality showed a tendancy to improve in most patients, and the degree of improvement showed significant correlation with the amount of clinical improvement (p < 0.01).

• 대한핵의학회지
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• 제39권6호
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• pp.413-420
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• 2005

목적: 수용체 결합능 정량화를 위해서는 방사성추적자의 동태를 충분히 관찰하기 위해서 보통 뇌 PET 영상을 60-120분 정도 얻어야 한다. 이처럼 장기간 PET 영상을 얻게 되는 경우 보통 피험자의 수의적/불수의적 움직임을 피할 수 없고 이러한 피험자의 머리 움직임은 재구성된 PET 영상의 공간해상도를 저하시키고 측정된 방사능 농도의 정확성을 떨어뜨리는 요인이 된다. 이 연구에서는 동적 영상 정보만을 이용하여 피험자의 머리 움직임을 보정할 수 있는 방법을 개발하고 이를 피험자의 움직임이 불가항력적인 뇌활성화 도파민 D2 수용체 영상에 적용하여 움직임 보정이 리간드 결합능 및 외부 자극에 의한 도파민 유리(release) 정량화에 미치는 영향을 평가하였다. 대상 및 방법: 4명의 정상인 자원자에서 비디오 게임에 의한 도파민 유리를 평가하기 위한 실험으로 순간+연속 주입법을 이용하여 얻은 $[^{11}C]raclopride$ PET 영상을 이용하였으며 실제로 도파민 유리를 계산하기 위해서 필요한 프레임들만을 선별해서 영상 정합 기법을 적용하였다. 즉, $[^{11}C]raclopride$을 투여한 후 선조체에서의 리간드의 특이적 결합이 항정상태(steady state)에 최초로 도달하는 과제 수행 전 (30-50 분) 영역과, 비디오 게임 과제에 의해 도파민이 유리된 후 다시 항정상태에 도달하는 70-90분, 비디오 게임을 멈춘 후 다시 항정상태에 도달하는 110-120 분 데이터에만 움직임 보정 기법을 적용하는 방식이다. 각 항정상태 구간은 보통 2-4개의 프레임으로 구성되므로 먼저 이들 프레임들간의 영상정합을 수행(intra-condition registration)하여 평균 영상을 만들고 이들 평균 영상들을 정합하여 최종적으로 움직임 보정(inter-condition registration)을 하였다. 게임 수행 전후의 도파민유리를 평가하기 위하여 머리 움직임 보정 전후의 게임 과제 수행 전후의 결합능 백분율 변화를 구하였으며 각 조건에 대한 결합능 파라미터 영상을 구하고 움직임 보정 전후의 결합능 영상의 화소별 차이를 SPM2를 이용한 t-test(쌍체 검정)로 알아보았다. 결과: 움직임 보정 전후의 영상을 비교하였을 때, 움직임 보정 전 영상에서, 게임 수행시 영상이 게임을 위한 스크린 위치에 따른 시야 변동으로 게임 수행전 영상에 비하여 앞쪽 아래로 기울어져 있음을 알 수 있었으며 이러한 경향은 대상 피험자 모두에서 관찰되었다. 보정 전 영상으로부터 측정된 비디오 게임에 의한 도파민 유리는 putamen에서 29%, caudate head에서 57%, ventral striatum에서 17% 였으나, 보정 후 영상으로부터 구한 도파민 유리는 이들 영역에서 각각 3.9%, 14,1%, 0.6%로 움직임 보정을 하지 않은 경우 선조체 모든 구소물에서 결합능 감소, 즉 게임에 의한 도파민 유리가 과대평가됨을 알 수 있다. SPM 분석결과에서도 움직임을 보정하지 않은 영상을 이용한 경우, 선조체 구조물에서의 결합능 감소와 움직임에 의한 영상강도 저하가 복합적으로 영향을 주어 결합능 차이가 매우 유의하게 평가되었으나 움직임 보정 후 영상을 이용하여 비교한 경우, 결합능 변화가 선조체 영역에서 국한되어 나타나며 그 유의성이 움직임 보정 전에 비하여 낮음을 알 수 있었다. 결론: 뇌활성화 과제 수행시에 동반되는 피험자의 머리 움직임에 의하여 도파민 유리가 과대평가되었으며 이는 이 연구에서 제안한 영상정합을 이용한 움직임 보정기법에 의해서 개선되었다.