• The Plant Pathology Journal
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• 제36권1호
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• pp.43-53
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• 2020

Ralstonia solanacearum (Rso) is a causal agent of bacterial wilt in Solanaceae crops worldwide including Republic of Korea. Rso virulence predominantly relies on type III secreted effectors (T3Es). However, only a handful of Rso T3Es have been characterized. In this study, we investigated subcellular localization of and manipulation of plant immunity by 8 Rso T3Es predicted to harbor a nuclear localization signal (NLS). While 2 of these T3Es elicited cell death in both Nicotiana benthamiana and N. tabacum, only one was dependent on suppressor of G2 allele of skp1 (SGT1), a molecular chaperone of nucleotide-binding and leucine-rich repeat immune receptors. We also identified T3Es that differentially regulate flg22-induced reactive oxygen species production and gene expression. Interestingly, several of the NLS-containing T3Es translationally fused with yellow fluorescent protein accumulated in subcellular compartments other than the cell nucleus. Our findings bring new clues to decipher Rso T3E function in planta.

• Toxicological Research
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• 제8권2호
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• pp.161-170
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• 1992

The objectives of this sutdy were to investigate the effects of 8-fluorociprofloxacin(8-FCP) on the central nervous system (CNS) and to compare with those of ciprofloxacin(CP). The $LD_{50}$ values of intravenous 8-FCP were similar or slightly lower in rat (M;203.6mg/kg, F;186.1mg/kg)and markedly lower in mice (M;126.5mg/kg, F;163.1mg/kg), as compared to those of CP. However, no recognizable differences in the clinical signs and recovery were found between 8-FCP and CP in both species. In combination with fenbufen, the convulsive liability of 8-FCP was higher than that of CP. At an intravenous dose of 10mg/kg, 8-FCP provoked convulsive signs and subsequent death in mice, whereas CP produced convulsion at a dose of 40mg/kg. The hexobabital -induced sleeping time was markedly lengthened by the oral administration of 8-FCP, but slightly increased by CP. In addition, the two quinolone derivatives had analgesic effects. The analgesic activity of 8-FCP was approximately two times higher than that at CP. However, both 8-FCP and CP had little effects of pentylenetetrazole-or strychnine-induced convulsion and muscle relaxation. Our finding that 8-FCP had more remarkable CNS effects than CP strongly suggests that there should be differences in the pharmacokinetic characteristics and/or in the binding affinity for specific biologic targets, or receptors, in the CNS.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.168-177
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• 2019

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.

• The Korean Journal of Physiology and Pharmacology
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• 제23권4호
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• pp.281-289
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• 2019

Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

• 생명과학회지
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• 제18권1호
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• pp.120-128
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• 2008

본 연구에서는 지금초 열수 추출물(WEEH)의 처리에 의한 TRAIL 저항성 인체 위암세포의 증식 억제와 연관된 apoptosis유발에 관한 기전 해석을 시도하였다. 이를 위하여 AGS 세포주가 사용되었으며 다음과 같은 결과를 얻었다. 본 연구에서 조사된 범위 내에서의 TRAIL (200 ng/ml) 및 WEEH (0.04 mg/ml)의 단독 처리에 의한 AGS 세포에 유의적인 세포 독성을 나타내지 않았다. 그러나 TRAIL 및 WEEH의 혼합 처리는 WEEH의 처리 농도의존적으로 AGS 세포의 증식을 억제하였으며, 이는 apoptosis 유발에 의한 것임을 MTT assay, 핵의 염색질 응축 및 세포주기 sub-G1기에 속하는 세포빈도의 증가 등으로 확인하였다. TRAIL 및 WEEH 혼합 처리에 의한 apoptosis 유발 기전의 해석을 위하여 다양한 생화학적 분석법에 의하여 조사된 결과에 의하면, TRAIL 및 WEEH 혼합처리에 의한 caspase-8의 활성화에 의한 BID의 truncation화 및 이와 연관된 미토콘드리아 기능의 손상에 따른 caspase-9의 활성화와 연관성이 있었다. 이러한 미토콘드리아 기능 손상 및 caspase-9의 활성화는 Bcl-2, Bcl-xL, XIAP 및 cIAP-2등과 같은 anti-apoptotic 인자들의 발현 저하와 연관성이 있는 것이며, 이로 인한 caspase-3의 활성화에 의한 PARP 단백질의 단편화 유도로 apoptosis가 일어난 것으로 예측되어 진다. 비록 부가적인 연구들이 요구되어지지만, 본 연구의 결과는 TRAIL저항성 암세포의 항암전략에 지금초 추출물의 적용 가능성을 보여주는 것으로서 지금초의 항암작용의 규명에 중요한 자료를 제공하여 줄 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제44권1호
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• pp.183-190
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• 1997

Tocolytics 임신부의 조기진통시 치료제로 많이 사용되는 약제지만 드물게는 폐부종을 일으켜 치명적일 수 있다. Tocolytics가 폐부종을 일으키는 기전은 용적증가, 교질삼투압의 감소, 심근 손상, 모세혈관 내막의 손상등에 의해 발생한다고 설명되고 있으나 아직 불확실한 상태이며 폐부종 발생의 양대 기전인 정수압적 폐부종과 투과성 폐부종의 양상이 모두 관여하는 것으로 알려져 있다. 또한 임산부가 다산부이거나 다태아 임신인 경우, 임신중 수액공급을 많이 받은 경우, 심장 질환이 동반된 경우, 감염이 동반된 경우, 동시에 steroid나 MgSO4로 치료 받은 경우등이 tocolytics 사용시 폐부종이 쉽게 발생될 수 있는 선행요인으로 작용함이 알려져왔다. 저자들은 조기진통이 있어 tocolytics인 ritodrine 치료후 정상분만하였으나 분만후 급속히 진행하는 폐부종이 발생한 30세 여자 환자를 경험하였기에 문헌고찰과 함께 보고하는 바 이다.

• 분석과학
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• 제24권6호
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• pp.533-543
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• 2011

hERG (human ether-a-go-go related gene) 이온채널은 심장 재분극의 중요 요소이며 이 채널의 저해제는 부정맥과 돌연사를 유발할 수 있다. 따라서, 신약개발과정에서 후보물질이 hERG 이온채널의 잠재적인 저해제일 경우에는 심장독성 부작용을 유발하므로, 이를 최소화하고자 많은 노력이 집중되고 있다. 본 연구는 HEK(인간 배아 신장)세포에서 얻은 202개 유기화합물의 $IC_{50}$ 데이터를 이용하여 2차원 구조-활성의 정량적 관계(2D-QSAR)방법으로 예측하는 모델을 개발하였다. hERG이온채널 저해제의 기계 학습방법으로는 다중선형회귀(Multiple Linear Regression), 서포트 벡터 머신(Support Vector Machine: SVM)방법과 인공신경망(Artificial Neural Network)방법이며, 교차검증을 적용한 모집단 기반 전진선택(forward selection)방법과 결합하여 각 학습모델에 적합한 최적의 표현자들을 결정하였다. 가장 우수한 방법은 14종의 표현자를 사용한 인공신경망방법($R^2_{CV}$=0.617, RMSECV=0.762, MAECV=0.583)이었고, 다중선형회귀방법을 통해서 hERG이온채널 저해물질의 구조적 특징과 수용체와의 상호작용을 설명할 수 있다. QSAR모델의 검증은 교차검증과 Y-scrambling test방법으로 수행하였다.

• Journal of Chest Surgery
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• 제20권1호
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• pp.112-127
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• 1987

Myasthenia gravis is a neuromuscular transmission function disorder characterized by fatigue and weakness of voluntary muscles. This muscular weakness is intensified by activity and stress, and improved by the use of anticholinesterase compounds. It was initially described by Erb in 1879 and later named myasthenia gravis by Jolly in 1895. Although the pathogenesis is Known to be an autoimmune related reduction in the number of available acetylcholine receptors at neuromuscular junctions, the role of thymus in myasthenia gravis is still unclear and under investigation. Thymectomy in the management of myasthenia gravis has become increasingly important since Dr. Blalock observed in 1939 that some patients with thymic tumors and myasthenia gravis improved following thymectomy. A clinical study of 102 cases of myasthenia gravis was performed at Yonsei University College of Medicine. Seoul, Korea from Jan. 1976 to Jun. 1986. In order to determine which factors are of prognostic significance, attention is focused upon pre-operative patient evaluation, problems in operative and post-operative care, and long-term follow-up observations. The results were as follows: 1. The sex distribution was 67 females and 35 males, the mean age of onset was 28.95*1.69 years, and the maximal incidence occurred between 21 and 40 years of age [56 cases: 54.9%]. 2. Clinical manifestations of ocular symptoms were seen to 70 patients [68.6%] extremities weakness in 33 [32.3%], bulbar weakness in 29 [28.4%], and dyspnea in 13 [12.7%]. 3. Study cases more than two thirds were classified as mild types [MG 1 and MG 11A] and 6 cases as grave [MG 1V] based on the modified Osserman`s classification system, 4. Thymectomy was performed in 19 cases which presented in severe myasthenia symptoms and showed no improvement with cholinergic drugs. Histologic examination of the excised thymus glands revealed no abnormalities in 4 cases, thymic hyperplasia in 5, benign thymoma in 5, and malignant thymoma in 5. 5. Immediate post-operative complications included 2 cases of pneumothorax which were treated by tube thoracostomies, there was no operative mortality. 6. The response to cholinergic drugs in 36 cases younger than 20 years old and in 27 cases older than 40 years was relatively poor, while that in 35 cases between the ages of 21 and 40 years old was good. 7. Thirty of 39 cases in groups IIB, III & IV improved markedly with medical or surgical management while only 16 of 59 cases in the mild groups [I and IIA] improved, almost all surgical cases improved in all categories. 8. There were 5 deaths. occurring between 7 months and 3 years 3 months of treatment of myasthenia gravis. The causes of death were myasthenic crisis in 2 cases, respiratory failure due to candidiasis & radiation pneumonitis in one case, cerebral hemorrhage due to high blood pressure in two case.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1725-1729
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• 2013

Background: Breast cancer is the second leading cancer causing death in women. Circulating tumor cells are among the prognostic factors while tumor markers are of diagnostic value and can be used for follow-up. The aim of this study was to investigate the correlation between the prognostic significance of the serum CA15-3 levels, number of circulating tumor cells and histopathological tumor factors. Materials and Methods: Thirty patients recently diagnosed with breast cancer were included in the study. Number of circulating tumor cells and serum CA15-3 level were assessed when metastasis was detected and diagnostic value was assessed. Presence of associations with estrogen and progesterone receptors, c-erbB2, Ki-67 proliferation index and histological grade were also evaluated. Results: Median overall survival of the patients with serum CA15-3 levels of >108 ng/dl was 19 months whereas for those with a low serum level it was 62 months. Median overall survival for CTC ${\geq}5$ vs CTC<5 patients was 19 months and 40 months respectively. The difference between the two groups was statistically significant. Conclusions: Prognostic significance of the CTC count and CA15-3 levels in metastatic breast cancer patients was demonstrated.