• Reproductive and Developmental Biology
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• 제31권4호
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• pp.267-272
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• 2007

Human embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and have the capacity to differentiate into various types of cells in the body. Hence, these cells may potentially be an indefinite source of cells for cell therapy in various degenerative diseases including neuronal disorders. For clinical applications of human ES cells, directed differentiation of these cells would be necessary. The objective of this study is to develop the culture condition for the expansion of neural precursor cells derived from human ES cells. Human ES cells were able to differentiate into neural precursor cells upon a stepwise culture condition. Neural precursor cells were propagated up to 5000-fold in cell numbers over 12-week period of culture and evaluated for their characteristics. Expressions of sox1 and pax6 transcripts were dramatically up-regulated along the differentiation stages by RT-PCR analysis. In contrast, expressions of oct4 and nanog transcripts were completely disappeared in neural precursor cells. Expressions of nestin, pax6 and sox1 were also confirmed in neural precursor cells by immunocytochemical analysis. Upon differentiation, the expanded neural precursor cells differentiated into neurons, astrocytes, and oligodendrocytes. In immunocytochemical analysis, expressions of type III ${\beta}$-tubulin and MAP2ab were observed Presence of astrocytes and oligodendrocytes were also confirmed by expressions of GFAP and O4, respectively. Results of this study demonstrate the feasibility of long-term expansion of human ES cell-derived neural precursor cells in vitro, which can be a potential source of the cells for the treatment of neurodegenerative disorders.

• The Korean Journal of Physiology and Pharmacology
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• 제24권3호
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• pp.193-201
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• 2020

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

• Journal of Yeungnam Medical Science
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• 제30권2호
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• pp.116-119
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• 2013

A burnt-out prostate cancer tumor is a very rare clinical entity. The term 'burnt-out' refers to a primary tumor that has spontaneously and nearly completely regressed without treatment. Since metastasis of prostate cancer is usually encountered in the presence of advanced disease, distant metastasis with an undetectable primary tumor is very rare. We report herein a case of a burnt-out prostate cancer tumor that metastasized to the thoracic (T) spine and caused cord compression. A 66-year-old man visited the Emergency Department due to weakness of both legs for the past two days. His blood and urine tests were normal at the time. His spine magnetic resonance imaging (MRI) scans looked like bone metastasis that involved the T-7 vertebral body and a posterior element, and caused spinal cord compression. Other images, including from the brain MRI, neck/chest/abdomino-pelvic computed tomography (CT) scan and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and endoscopy, revealed no lesions that suggested malignancy. After total corpectomy T-7 and screw fixation/fusion at T5 to T10, the pathology report revealed a metastatic carcinoma that was strongly positive for prostate-specific antigen (PSA). The serum PSA value was 1.5 ng/mL. The transrectal 12-core prostate biopsy and ultrasonography showed no definitive hypoechoic lesion, but one specimen had slight (only 1%) adenocarcinoma with a Gleason score of 6 (3+3). The final diagnosis was burned-out prostate cancer with an initial normal PSA value. Although metastatic disease with an unknown primary origin was confirmed, a more aggressive approach in seeking the primary origin could provide a more specific treatment strategy and greater clinical benefit to patients.

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.151-156
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• 2010

This study was performed to investigate the role of glutamate neurotransmitter system on gastrointestinal motility in a middle cerebral artery occlusion (MCAO) model of rats. The right middle cerebral artery was occluded by surgical operation, and intestinal transit and geometric center as a parameter of gastrointestinal motility and expression of c-Fos protein in the insular cortex and cingulate cortex were measured at 2 and 12 h after MCAO. Intestinal transit was $66.3{\pm}7.5%$ and $62.3{\pm}5.7%$ 2 and 12 h after sham operation, respectively, and MCAO significantly decreased intestinal transit to $39.0{\pm}3.5%$ and $47.0{\pm}5.1%$ at 2 and 12 h after the occlusion, respectively (p<0.01). The geometric center was $5.6{\pm}0.4$ and $5.2{\pm}0.9$ at 2 and 12 h after sham operation, respectively, and MCAO significantly decreased geometric center to $2.9{\pm}0.8$ and $3.0{\pm}0.3$ at 2 and 12 h after the occlusion, respectively (p<0.01). In control animals, injection of atropine decreased intestinal transit to $35.9{\pm}5.2%$, and injection of glutamate NMDA receptor antagonist, MK-801, decreased intestinal transit to $28.8{\pm}9.5%$. Pretreatment with MK-801, a glutamate NMDA receptor antagonist, in the MCAO group decreased intestinal transit to $11.8{\pm}3.2%$, which was significantly decreased compared to MCAO group (p<0.01). MCAO markedly increased the expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO, and pretreatment with MK-801 produced marked reduction of c-Fos protein expression compared to MCAO group (p<0.01). These results suggest that modulation of gastrointestinal motility after MCAO might be partially mediated through a glutamate NMDA receptor system.

• 대한의용생체공학회:의공학회지
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• 제38권1호
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• pp.9-15
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• 2017

Recently, flexible cages have been introduced in an attempt to absorb and reduce the abnormal load transfer along the anterior parts of the spine. They are designed to be used with the pedicle screw systems to allow some mobility at the index level while containing ROM at the adjacent level. In this study, a finite element (FE) study was performed to assess biomechanical efficacies of the flexible cage when combined with pedicle screws with flexible rods. The post-operated models were constructed by modifying the L4-5 of a previously-validated 3-D FE model of the intact lumbar spine (L2-S1): (1) Type 1, flexible cage only; (2) Type 2, pedicle screws with flexible rods; (3) Type 3, interbody fusion cage plus pedicle screws with rigid rods; (4) Type 4, interbody fusion cage plus Type 2; (5) Type 5, Type 1 plus Type 2. Flexion/extension of 10 Nm with a compressive follower load of 400N was applied. As compared to the Type 3 (62~65%) and Type 4 (59~62%), Type 5 (53~55%) was able to limit the motion at the operated level effectively, despite moderate reduction at the adjacent level. It was also able to shift the load back to the anterior portions of the spine thus relieving excessively high posterior load transfer and to reduce stress on the endplate by absorbing the load with its flexible shape design features. The likelihood of component failure of flexble cage remained less than 30% regardless of loading conditions when combined with pedicle screws with flexible rods. Our study demonstrated that flexible cages when combined with posterior dynamic system may help reduce subsidence of cage and degeneration process at the adjacent levels while effectively providing stability at the operated level.

• 대한약리학회지
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• 제13권2호
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• pp.19-34
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• 1977

1) 마취가토(痲醉家兎) 및 묘(猫)에서 경뇌막외강(硬腦膜外腔)을 통(通)한 가압방법(加壓方法)으로 두개내압상승(頭蓋內驅上昇)과 혈압(血壓) 및 심박(心搏)과의 관계(關係)를 조사(調査)하였다. 2) 양동물(兩動物)에서 두개내압(頭盞內壓)을 상승(上昇)시켜 두개내압(頭蓋內壓)과 혈압(血壓)의 차(差)가 아주 적어지면 현저(顯著)한 혈압상승(血壓上昇)이 나타났다. 3) 양동물(兩動物)에서 두개내압(頭盞內壓)이 혈압(血壓)보다 높아지면 현저(顯著)한 혈압하강(血壓下降)과 현저(顯著)한 일시적(一時的)인 심박감소(心搏減少)가 나타났다. 4) Reserpine 처리동물(處理動物)에서는 두개내압상승(頭蓋內驅上昇)은 혈압하강(血壓下降), 심박감소(心搏減少)를 일으켰다. 5) 6-Hydroxydopamine 처리(뇌내)동물(處理(腦內)動物)에서는 두개내압상승(頭蓋內驅上昇)에 의한 혈압상승(血壓上昇)은 비처리동물(非處理動物)에 비(比)하여 약(弱)하였다. 6) Reserpine 처리동물(處理動物)의 측뇌실내(側腦室內)에 norepinephrine을 투여(投與)한 후(後)에는 두개내압상승(頭蓋內驅上昇)은 현저(顯著)한 혈압상승(血壓上昇)을 일으켰다. 7) 두개내압상승(頭蓋內驅上昇)에 의한 혈압상승(血壓上昇)은 두개내압상승(頭蓋內驅上昇)으로써 뇌내(腦內) noradrenergic neuron이 자극(刺戟)되여 norepinephrine 유리(遊離)가 증가(增加)한 결과(結果) 일어나는 것으로 추리(推理)하였다.

• Journal of Korean Neurosurgical Society
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• 제63권2호
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• pp.188-201
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• 2020

Objective : The purpose of this study was to suggest that computed tomography angiography (CTA) is valuable as the only preliminary examination for mechanical thrombectomy (MT). MT after single examination of CTA including noncontrast computed tomography (NCCT) and maximum intensity projection (MIP) improves door-to-puncture time as well as results in favorable outcomes. Methods : A total of 157 patients who underwent MT at Dong Kang Medical Center from April 2015 to March 2019 were divided into two groups based on the examination performed prior to MT : CTA group who underwent CTA with NCCT and MIP, and NCCT+magnetic resonance image (MRi) group who underwent MRI including perfusion images after NCCT. In the two groups, time to CTA imaging or NCCT+MRi imaging after symptom onset, and time to arterial puncture and reperfusion were characterized as time-related outcomes. The evaluation of vascular recanalization after MT was defined as a modified thrombolysis in cerebral infarction (mTICI) scale. National Institutes of Health Stroke Scale (NIHSS) was assessed at the time of the visit to the emergency room and modified Rankin Scale (mRS) was assessed after 90 days. Results : Typically, there were 34 patients in the CTA group and 33 patients in the NCCT+MRi group. A significantly shorter delay for door-to-puncture time was observed (mean, 86±22.1 vs. 176±47.5 minutes; <0.01). Also, a significantly shorter door-to-imege time in the CTA group was observed (mean, 13±6.8 vs. 93±30.8 minutes; p<0.01). Moreover, a significantly shorter onset-to-puncture time was observed (mean, 195±128.0 vs. 314±157.6 minutes; p<0.01). Reperfusion result of mTICI ≥2b was 100% (34/34) in the CTA group and 94% (31/33) in the NCCT+MRi group, and mTICI 3 in 74% (25/34) in the CTA group and 73% (24/33) in the NCCT+MRi group. Favorable functional outcomes (mRS score ≤2 at 90 days) were 68% (23/34) in the CTA group and 60% (20/33) in the NCCT+MRi group. Conclusion : A single-phase CTA including NCCT and MIP images was performed as a single preliminary examination, which led to a reduction in the time of the procedure and resulted in good results of prognosis. Consequently, it is concluded that this method is of sufficient value as the only preliminary examination for decision making.

• Journal of Korean Neurosurgical Society
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• 제63권5호
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• pp.579-589
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• 2020

Objective : No optimum genetic rat Huntington model both neuropathological using an adeno-associated virus (AAV-2) vector vector has been reported to date. We investigated whether direct infection of an AAV2 encoding a fragment of mutant huntingtin (AV2-82Q) into the rat striatum was useful for optimizing the Huntington rat model. Methods : We prepared ten unilateral models by injecting AAV2-82Q into the right striatum, as well as ten bilateral models. In each group, five rats were assigned to either the 2×10¹² genome copies (GC)/mL of AAV2-82Q (×1, low dose) or 2×10¹³ GC/mL of AAV2-82Q (×10, high dose) injection model. Ten unilateral and ten bilateral models injected with AAV-empty were also prepared as control groups. We performed cylinder and stepping tests 2, 4, 6, and 8 weeks after injection, tested EM48 positive mutant huntingtin aggregates. Results : The high dose of unilateral and bilateral AAV2-82Q model showed a greater decrease in performance on the stepping and cylinder tests. We also observed more prominent EM48-positive mutant huntingtin aggregates in the medium spiny neurons of the high dose of AAV2-82Q injected group. Conclusion : Based on the results from the present study, high dose of AAV2-82Q is the optimum titer for establishing a Huntington rat model. Delivery of high dose of human AAV2-82Q resulted in the manifestation of Huntington behaviors and optimum expression of the huntingtin protein in vivo.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.243-251
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• 2000

In order to provide a basis for studying the molecular mechanism of pharmacological action of local anesthetics and to develop a fluorescence spectroscopic method which can detect the microviscosity of native and model membranes using intramolecular excimerization of 1,3-di(l-pyrenyl)propane (Py-3-Py), we examined the effect of lidocaine HCl on the microviscosity of model membranes of phosphatidylcholine fraction extracted from synaptosomal plasma membrane vesicles (SPMVPC). The excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in liquid paraffin was a simple linear function of $T/{\eta}.$ Based on this calibration curve, the microviscosity values of the direct probe environment in SPMVPC model membranes ranged from $234.97{\pm}48.85$ cP at $4^{\circ}C$ to %19.21{\pm}1.11$ cP at $45^{\circ}C.$ At $37^{\circ}C,$ a value of $27.25{\pm}0.44$ cP was obtained. The lidocaine HCl decreased the microviscosity of SPMVPC model membranes in a concentration-dependent manner, with a significant decrease in microviscosity value by injecting the local anesthetic even at the concentration of 0.5 mM. These results indicate that the direct environment of Py-3-Py in the SPMVPC model membranes is significantly fluidized by the lidocaine HCl. Also, the present study explicitly shows that an interaction between local anesthetics and membrane lipids is of importance in the molecular mechanism of pharmacological action of lidocaine HCl.

• 한국의료질향상학회지
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• 제17권1호
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• pp.79-88
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• 2011

Background : Evidence-based guidelines are now used for enteral nutrition(EN) in neurosurgical intensive care unit patients who mostly depend on EN. This study compared and analyzed the nutritive conditions of patients before and after they underwent guideline based nutritional interventions in order to determine whether using these guidelines improved their calorie supply. Methods : Data on the patients' nutritional requirements, maximum calorie supply through EN, serum albumin level, and total lymphocyte count were collected and analyzed using SAS version 9.1.3. All the statistical analyses were performed at a significance level of P<0.05. Result : The maximum calorie supply through EN was $923.1{\pm}359.7$ kcal before the intervention and $1254.4{\pm}196.3$ kcal after the intervention; this difference was statistically significant(P<0.05). The ratio of nutritional requirements to maximum calorie supply through EN was $55.5{\pm}22.4%$ and $74.2{\pm}13.9%$ before and after the intervention, respectively; this difference was statistically significant(P<0.05). This indicates a 19% increase in the ratio after the nutritional intervention. The serum albumin level also significantly increased from $2.7{\pm}0.6g/dL$ before the intervention to $3.2{\pm}0.4g/dL$ after the intervention(P<0.05). The total lymphocyte count slightly increased from $1267.7{\pm}728.2cells/mm^3$ before the intervention to $1801.9{\pm}1211.5cells/mm^3$ after the intervention; this difference was not statistically significant. Conclusion : The results showed that using the evidence-based feeding guidelines for interventions increased the calorie supply and improved the patients' nutritive conditions from moderate malnutrition to mild malnutrition.