• 한국동물학회지
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• 제38권4호
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• pp.542-549
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• 1995

Extracellular matrix(ECM) 단백질이 SK-N-SH 및 IMR-32 세포주가 신경계 세포로 분화되는 데 미치는 영향을 조사하였다. Laminin과 collagen으로 도말한 배양기에서 7일간 배양했을 때 SK-N-SH세포는 잘 발달된 신경측색생장을 보였으나 IMR-32세포는 뚜렷한 형태변화를 나타내지 않았다. 왜 IMR-32세포가 ECM 단백질에 반응을 하지 않는가를 규명하기 위하여 ECM단백질에 의한 초기 신호전달기작을 두 세포주에서 분석하였다. ECM 단백질을 도말한 배양기에 세포를 깔았을 때 한시간 만에 tyrosine 인산화된 단백질이 두 세포 모두 증가함을 볼 수 있었다. 아울러 focal adhesion kinase(FAK)의 tyrosine 인산화도 두 세포주 모두에서 증가하였다. 이러한 결과는 두 세포주가 ECM 단백질에 의한 초기 신호전달체계가 정상임을 의미한다. 신경세포 분화과정에 증가한다고 알려진 Bcl-2 및 NSE의 량을 ECM 단백질 처리후 조사하였을 때 SK-N-SH 세포주는 두 단백질이 증가 했지만 IMR-32 세포주는 변화가 없었다. 이러한 결과는 IMR-32 세포주가 ECM 단백질에 반응하지 않는 것이 ECM 단백질에 의한 신호전달체계에 문제가 있다기 보다 신경계세포로 분화되는 데 필요한 유전인자의 발현조절에 문제가 있음을 시사한다.

• 대한의생명과학회지
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• 제3권1호
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• pp.11-20
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• 1997

신경아세포종 세포 분화의 조절에 대한 연구는 아직 초기 단계에 불과하나 신경아세포종양의 임상적인 치료에 매우 중요한 기초가 된다. 본 연구는 신경아세포종 세포의 분화를 유도 할 수 있는 유용한 시약을 찾아내고자 하는 노력의 일환으로, 잘 알려진 DNA 합성 억제제가 신경 아세포종의 분화를 유도할 수 있는지를 살펴보고자 신경아세포종양 세포의 형태적, 생화학적 및 유전자 발현에 미치는 효과를 살펴보았다. 신경아세포종양으로부터 수립된 세포주, IMR-32 세포에 DNA 합성 억제제인 sodium butyrate, hydroxyurea, cytosine arabinoside를 각각 처리한 결과 처리하지 않은 대조군과는 달리 정상신경 세포 분화시 볼 수 있는 신경 돌기의 성장이 유도됨을 관찰할 수 있었으며 ,신경 전달 물질인 acetylcholine의 합성 효소인 choline acetyltransferase의 활성도가 현저히 증가되었다. 또한DNA합성 억제제를 처리하지 않은 IMR-32세포에서 탐지되지 않았던 c-myc 유전자의 발현이 시약 처리시 확연히 탐지됨을 관찰할 수 있었다. 이러한 실험 결과들은 DNA합성 억제제가 IMR-32세포의 성장을 억제하고 분화를 유도했음을 보여준 것이며, 어린 아이 시기에 많이 발병되는 신경아세포종양의 급속한 악성화나 전이의 억제기전을 제시해 줄 수 있으리라 생각한다.

• Biomolecules & Therapeutics
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• 제14권3호
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• pp.137-142
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• 2006

Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. In this study we investigated the role of apigenin in the production of reactive oxygen species (ROS) through the modulation of activity of $K^+-Cl^-$-cotransport (KCC) in IMR-32 human neuroblastoma cells. Apigenin induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity, which was markedly prevented by different kinds of KCC inhibitors (calyculin-A, genistein and $BaCl_2$). These results indicate that KCC is functionally present, and activated by apigenin in the IMR-32 cells. Treatment with apigenin also induced a sustained increase in the level of intracellular ROS. The KCC inhibitors also significantly inhibited the apigenin-induced ROS generation. Taken together, these results suggest that apigenin can modulate ROS generation through the activation of a membrane ion transporter, KCC. These results further suggest that the alteration of KCC activity may play a role in the mechanism of degenerative diseases and/or carcinogenesis in neuronal tissues through the regulation of ROS production.

• Journal of Genetic Medicine
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• 제1권1호
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• pp.45-50
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• 1997

Neuroblastoma, a pediatric malignant neoplasm of neural crest origin, has a wide range of clinical virulence. The mechanisms contributing to the development of neuroblastomas are largely unclear, but non-random chromosomal changes identified over the past years suggest the involvement of genetic alterations. Amplification of the human N-myc proto-oncogene is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions (HSRs) of aggressively growing neuroblastomas. N-myc maps to chromosome 2 band 24, but HSR have never been observed at this band, suggesting transposition of N-myc during amplification. We have constructed and analyzed the region-specific painting probe for HSR in neuroblastoma IMR-32 to determine the derivative chromosomes. Microdissection was performed on HSR using an inverted microscope with the help of microglass needles and an micromanipulator. We pretreated the microdissected fragments with Topoisomerase I which catalyzes the relaxation of supercolled DNA, and performed two initial rounds of DNA synthesis with T7 DNA polymerase followed by conventional PCR to enable the reliable preparation of Fluorescent in situ hybridization probe from a single microdissected chromosome. With this method, it was possible to construct the region-specific painting probe for HSR. The probe hybridized specifically to the HSRs of IMR-32, and to 2p24, 2p13 of normal chromosome. Our results suggest there was coamplification of N-myc together with DNA of the chromosome 2p24 and 2p13. Moreover, the fluorescent signals for the amplified chromosomal regions in IMR-32 cells were also easily recognized at a Thus this painting probe can be applied to detect the similar amplification of N-myc in neuroblastoma tissue, and the probe pool for HSR may be used to identify the cancer-relevant genes.

• 한국의학물리학회지:의학물리
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• 제32권4호
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• pp.92-98
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• 2021

Purpose: This study automatically discriminates homogeneous and structure edge regions on computed tomography (CT) images, and it evaluates the noise level and edge preservation ratio (EPR) according to the different types of iterative reconstruction (IR). Methods: The dataset consisted of CT scans of 10 patients reconstructed with filtered back projection (FBP), statistical IR (iDose⁴), and iterative model-based reconstruction (IMR). Using the 10th and 85th percentiles of the structure coherence feature, homogeneous and structure edge regions were localized. The noise level was estimated using the averages of the standard deviations for five regions of interests (ROIs), and the EPR was calculated as the ratio of standard deviations between homogeneous and structural edge regions on subtraction CT between the FBP and IR. Results: The noise levels were 20.86±1.77 Hounsfield unit (HU), 13.50±1.14 HU, and 7.70±0.46 HU for FBP, iDose⁴, and IMR, respectively, which indicates that iDose⁴ and IMR could achieve noise reductions of approximately 35.17% and 62.97%, respectively. The EPR had values of 1.14±0.48 and 1.22±0.51 for iDose⁴ and IMR, respectively. Conclusions: The iDose⁴ and IMR algorithms can effectively reduce noise levels while maintaining the anatomical structure. This study suggested automated evaluation measurements of noise levels and EPRs, which are important aspects in CT image quality with patients' cases of FBP, iDose⁴, and IMR. We expect that the inclusion of other important image quality indices with a greater number of patients' cases will enable the establishment of integrated platforms for monitoring both CT image quality and radiation dose.

• Animal cells and systems
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• 제9권4호
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• pp.191-198
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• 2005

The effects of 6-aminonicotinamide (6-AN) on viability of IMR32 neuroblastoma cells in the presence of ATP or $NAD^+$ have been investigated. 6-AN caused marked reduction in cell viability and similar observations were also made with cells treated with 6-AN+ATP. However, cells treated with $6-AN+NAD^+$ showed cell viability similar to untreated cells. Morphologically, 6-AN and 6-AN+ATP treated cells showed loss of neurites, polyhedric shapes, shrinkage of cell bodies and formation of lysed cells, while $6-AN+NAD^+$ cells did not show any such changes. The flow cytometry analysis demonstrated that 6-AN increased cell population in $G_0/G_1$ phase and decreased cell population in Sand $G_2/M$ phase following a 72 h exposure. Western blot analysis showed that 6-AN stimulated a substantial increase in the level of the cdk inhibitor $p27^{kip1}$, but lowered the levels of cdk2, cyclin E and p-Rb. However, cdc25A and p53R2 were not significantly affected. Immunofluorscence staining of $p27^{kip1}$, cdk2, cyclin E and p-Rb revealed close correlation between the signal observed in the Western blot analysis. 6AN+ATP treated cells showed similar results obtained with 6-AN treated cells in expression of cdk2, cyclin E, p-Rb proteins and $p27^{kip1}$, $6-AN+NAD^+$ cells showed greater expression of cdk2, cyclin E and p-Rb than those in 6-AN and 6-AN+ATP treated cells. The results suggest that 6-AN induced the $G_0/G_1$ phase arrest in IMR32 neuroblastoma cell lines through the increase of $p27^{kip1}$ and the decrease of cdk2, cyclin E and p-Rb.

• Neonatal Medicine
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• 제18권2호
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• pp.182-188
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• 2011

목적: 한국에서 최근 신생아사망률(NMR), 영아사망률(IMR)는 주산기, 신생아, 소아과 의료의 발전으로 현저한 개선을 이루었다. 본 연구는 한국에서 최근 5년간 IMR 중에서 NMR가 차지하는 비율을 알아보아, NMR의 개선이 IMR의 감소에 미친 영향을 알아보고자 한다. 방법: 한국 통계청의 출생 자료 및 신생아 및 영아에 관련된 통계와 보고서의 자료를 기초로 하였다. 2005-2009년 간 한국에서 영아사망 중에서 신생아 사망이 차지하는 비율의 변화와 출생 시의 출생체중와 임신나이에 따른 분포별 사망이 영아사망에 차지하는 비율을 조사하였다. 결과: 2005-2009년 간 한국의 총 출생 수는 감소하였으나, 미숙아 수, 저체중출생아(LBWI) 수, 극수제체중출생아(VLBWI) 수는 증가하였다. 연도별 신생아 및 영아 사망 수, NMR, IMR는 감소하였다. 전체 영아사망 중에서 신생아사망이 차지하는 비율은 2005년 57.1%, 2009년 56.3%로 전체적으로 반 이상을 차지하였다. 신생아사망 중에서는 후기 신생아사망 보다는 조기 신생아사망의 비율이 높았다. 연도별로 출생 시 정상체중아, LBWI, VLBWI, 미숙아 사망 수는 감소추세 이었다. 전체 영아사망 중에서 출생 시 정상체중아에서 사망과 출생 시 LBWI 사망의 비는 2005년 42.1:57.9, 2009년 44.2:55.8, 전체 영아사망 중에서 출생 시 만삭아에서 사망과 미숙아 사망의 비는 2005년 42.9:57.1, 2009년 44.6:55.4로 LBWI, 미숙아의 사망이 높았다. 5년간 평균 수치의 출생체중별, 임신나이별 신생아 사망 비율도 관찰하였다. 결론: 한국에서 저출산 시대에 총 출생 수는 감소하고 있지만, 미숙아 LBWI의 빈도는 증가 추세이다. 한국에서 전반적인 연도별 전체 신생아 및 영아사망 수의 감소와 NMR, IMR의 개선과 IMR에서 NMR이 차지하는 비율의 감소 추세 등이 고무적이지만, 아직도 IMR에서 NMR의 비율은 반 정도를 차지하고 있다. 향후 한국에서 IMR의 보다 좋은 개선을 위하여 NMR의 지속적인 감소가 필요할 것으로 사료되며, 이를 위해서 미숙아 LBWI, 이중에서도 고위험 신생아인 VLBWI와 임신나이 32주 미만의 미숙아의 예후를 더욱 향상해야 할 것이다. 본 자료를 향후 신생아 관리의 기초로 활용되기를 기대한다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.19-27
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• 1999

Apoptosis has been implicated in the pathophysiological mechanisms of various neurodegenerative diseases. In a variety of cell types, oxidative stress has been demonstrated to play an important role in the apoptotic cell death. However, the exact mechanism of oxidative stress-induced apoptosis in neuronal cells is not known. In this study, we induced oxidative stress in IMR-32 human neuroblastoma cells with tert- butylhydroperoxide (TBHP), which was confirmed by significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity. TBHP induced decrease in cell viability and increase in DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. TBHP also induced a sustained increase in intracellular $Ca^{2+}$ concentration, which was completely prevented either by EGTA, an extracellular $Ca^{2+}$ chelator or by flufenamic acid (FA), a non-selective cation channel (NSCC) blocker. These results indicate that the TBHP-induced intracellular $Ca^{2+}$ increase may be due to $Ca^{2+}$ influx through the activation of NSCCs. In addition, treatment with either an intracellular $Ca^{2+}$ chelator (BAPTA/AM) or FA significantly suppressed the TBHP-induced apoptosis. Moreover, TBHP increased the expression of p53 gene but decreased c-myc gene expression. Taken together, these results suggest that the oxidative stress-induced apoptosis in neuronal cells may be mediated through the activation of intracellular $Ca^{2+}$ signals and altered expression of p53 and c-myc.

• 여성건강간호학회지
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• 제27권4호
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• pp.286-296
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• 2021

Purpose: This study compared infant mortality and its associated factors between Korean and immigrant women using vital statistics gathered by Statistics Korea. Methods: Birth and death statistics from the period between 2009 and 2019 were extracted from the census of population dynamics data of the Microdata Integrated Service, Korea. Statistical data were derived from a complete survey and infant mortality was analyzed from mortality statistics data. Descriptive statistics were used for comparison. Results: The average infant mortality rate (IMR) of Korean women was 2.7 in Korea, which did not change significantly between 2009 and 2019; however, the IMR of immigrant women increased significantly in 2018 to 4.2 and subsequently decreased to 2.6 in 2019. Moreover, the age of Korean and immigrant women at the time of infant death gradually increased from 31.1 years and 25.9 years in 2009 to 32.8 years and 30.9 years in 2019, respectively. The gestational age was lower for deceased infants born to immigrant women (mean, 31.04 weeks; standard deviation [SD], 6.42; median, 30.00) compared to infants born to Korean women (mean, 31.71 weeks; SD, 6.48; median, 32.00). Immigrant women (91.7%) received slightly fewer antenatal care visits compared to Korean women (93.1%). Conclusion: It is vital to devise a plan to lower the IMR of immigrant women in Korea. Moreover, it is necessary to explore the factors related to infant mortality among immigrant women within the context of Korean societal situation, culture, and home environment.

• Archives of Pharmacal Research
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• 제22권4호
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• pp.404-409
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• 1999

The inhibitory effects of the constituents of Gastrodia elata Bl. (GE) on glutamate-induced apoptosis in human neuronal cells were investigated using IMR32 human neuroblastoma cells. Glutamate (GLU) induced DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. GLU also induced a slow and sustained increase in intracellular $Ca^{2+}$ concentration. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator, in a nominal $Ca^{2+}$ -free buffer solution abolished the GLU-induced intracellular $Ca^{2+}$ increase, indicating that GLU stimulated Ca2+ influx pathway in the IMR32 cells. BAPTA, an intracellualr $Ca^{2+}$ chelator, significantly inhibited the GLU-induced apoptosis assessed by the flow cytometry measuring hypodiploid DNA content indicative of apoptosis, implying that intracellular $Ca^{2+}$ rise may mediate the apoptotic action of GLU. Vanillin (VAN) and p-hydroxybenzaldehyde(p-HB), known constituents of GE, significantly inhibited both intracellular $Ca^{2+}$ rise and apoptosis induced by GLU. These results suggest that the apoptosis-inhibitory actions of the constituents of GE may account, at least in part, for the basis of their antiepileptic activities. These results further suggest that intracelluarl $Ca^{2+}$ signaling pathway may be a molecular target of the constituents of GE.