• Journal of Korean Neurosurgical Society
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• 제39권3호
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• pp.210-214
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• 2006

Objective : We investigate risk factors of cerebral microbleeds[MBs] and their relation to concomitant magnetic resonance[MR] findings in intracerebral hemorrhages[ICHs] patients. Methods : We studied 100 consecutive patients with primary ICH over a 1-year period. These patients underwent brain MR images using 3.0-T scanners within the first week of the hemorrhage. MBs and old hematomas were located and counted by using $T2^*-weighted$ gradient-echo MR imaging. We also counted lacunes and graded white matter and periventricular hyperintensity on T1- and T2-weighted spin-echo sequences. The association between MBs and vascular risk factors and MR abnormalities were analyzed. Results : MBs were seen in 77 of ICH patients, and their number ranged from 1 to 65 lesions [mean 11, median 6]. The locations of MBs were subcortex-cortex [40.6%], basal ganglia [26.7%], thalamus [14.1 %], brain stem [12.5%], and cerebellum [9.1 %]. Analysis of clinical data revealed that age, hypertension, history of stroke, and duration of hypertension were frequently associated with MBs. The incidence of lacunes, old hematomas, and advanced leukoaraiosis was significantly higher in the MBs group, compared with the patients without MBs. Conclusion : MBs are frequently observed in ICH patients with advancing age, chronic hypertension, and previous hemorrhagic stroke, and are also closely related with morphological signs of occlusive type microangiopathy, such as lacunar infarct and severe leukoaraiosis.

• Journal of Audiology & Otology
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• 제24권1호
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• pp.10-16
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• 2020

Background and Objectives:The blockage of adenosine receptors by caffeine changes the levels of neurotransmitters. These receptors are present in all parts of the body, including the auditory and vestibular systems. This study aimed to evaluate the effect of caffeine on evoked potentials using auditory brainstem responses (ABRs) and cervical vestibular-evoked myogenic potentials (cVEMPs) in a double-blind placebo-controlled study. Subjects and Methods: Forty individuals (20 females and 20 males; aged 18-25 years) were randomly assigned to two groups: the test group (consuming 3 mg/kg pure caffeine powder with little sugar and dry milk in 100 mL of water), and the placebo group (consuming only sugar and dry milk in 100 mL water as placebo). The cVEMPs and ABRs were recorded before and after caffeine or placebo intake. Results: A significant difference was observed in the absolute latencies of I and III (p<0.010), and V (p<0.001) and in the inter-peak latencies of III-V and I-V (p<0.001) of ABRs wave. In contrast, no significant difference was found in cVEMP parameters (P13 and N23 latency, threshold, P13-N23 amplitude, and amplitude ratio). The mean amplitudes of P13-N23 showed an increase after caffeine ingestion. However, this was not significant compared with the placebo group (p>0.050). Conclusions: It seems that the extent of caffeine's effects varies for differently evoked potentials. Latency reduction in ABRs indicates that caffeine improves transmission in the central brain auditory pathways. However, different effects of caffeine on auditory- and vestibular-evoked potentials could be attributed to the differences in sensitivities of the ABR and cVEMP tests.

• 대한청각학회지
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• 제24권1호
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• pp.10-16
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• 2020

Background and Objectives:The blockage of adenosine receptors by caffeine changes the levels of neurotransmitters. These receptors are present in all parts of the body, including the auditory and vestibular systems. This study aimed to evaluate the effect of caffeine on evoked potentials using auditory brainstem responses (ABRs) and cervical vestibular-evoked myogenic potentials (cVEMPs) in a double-blind placebo-controlled study. Subjects and Methods: Forty individuals (20 females and 20 males; aged 18-25 years) were randomly assigned to two groups: the test group (consuming 3 mg/kg pure caffeine powder with little sugar and dry milk in 100 mL of water), and the placebo group (consuming only sugar and dry milk in 100 mL water as placebo). The cVEMPs and ABRs were recorded before and after caffeine or placebo intake. Results: A significant difference was observed in the absolute latencies of I and III (p<0.010), and V (p<0.001) and in the inter-peak latencies of III-V and I-V (p<0.001) of ABRs wave. In contrast, no significant difference was found in cVEMP parameters (P13 and N23 latency, threshold, P13-N23 amplitude, and amplitude ratio). The mean amplitudes of P13-N23 showed an increase after caffeine ingestion. However, this was not significant compared with the placebo group (p>0.050). Conclusions: It seems that the extent of caffeine's effects varies for differently evoked potentials. Latency reduction in ABRs indicates that caffeine improves transmission in the central brain auditory pathways. However, different effects of caffeine on auditory- and vestibular-evoked potentials could be attributed to the differences in sensitivities of the ABR and cVEMP tests.

• BMB Reports
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• 제55권6호
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• pp.281-286
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• 2022

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

• 대한영상의학회지
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• 제81권4호
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• pp.985-989
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• 2020

클로르페나피르는 널리 사용되는 살충제이며 인간에게는 치명적일 수 있다. 그러나 중추신경계 침범을 동반한 클로르페나피르 중독은 거의 보고되지 않고 있다. 우리는 이전까지 드물게 보고된 클로르페나피르 중독에 의한 백질뇌병증 환자의 자기공명영상 소견을 보고하고자 한다. 약 2주 전에 클로르페나피르를 음독한 71세 남자 환자가 내원 2일 전부터 시작된 양측 하지위약감과 배뇨장애를 주소로 내원하였다. 시행한 뇌 자기공명영상에서는 뇌량, 속섬유막, 뇌줄기를 포함하는 영역에 양측성의 광범위한 뇌백질의 이상을 보였고, 척수 자기공명영상에서는 전반적인 척수에 고신호를 동반한 종창을 보였다.

• 대한방사선치료학회지
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• 제34권
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• pp.43-50
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• 2022

목 적: 총 두피 방사선치료 시 정상 뇌 조직을 최대한 보호할 수 있도록 접선조사를 극대화하는 치료계획 및 장비를 선정하고자 하였다. 대상 및 방법: 인체 모형에 총 두피를 구획하여 치료 부위를 설정하고, 나선형 토모테라피(Helical TomoTherapy, HT) 계획, Complete Block을 이용한 나선형 토모테라피(Helical TomoTherapy with Complete Block, HTCB) 계획 그리고 체적조절호형방사선치료(Volumetric Modulated Arc Therapy, VMAT) 계획을 수립하였다. 모든 치료계획은 처방 선량(40 Gy)의 95%가 들어가는 치료계획 용적이 체적의 95% 이상이 될 수 있도록, Dmax가 처방 선량의 110%를 넘지 않게 하였다. 치료계획은 뇌를 포함한 손상 위험 장기의 선량 비교를 실시하였으며 뇌 선량의 경우 Emami 등의 연구 결과의 정상조직 평가기준 체적을 참고하여 뇌 조직의 선량을 평가하였다. 결 과: HT, HTCB, VMAT 각각 뇌 조직 선량 D_33%는 21.68 Gy, 13.75 Gy, 20.89 Gy, D_67%는 7.06 Gy, 3.21 Gy, 7.84 Gy, D100%는 3.14 Gy, 1.75 Gy, 3.84 Gy, D_mean은 16.64 Gy, 11.78 Gy, 16.64 Gy로 HTCB plan에서 전반적으로 선량이 낮았으며, 저선량은 5 Gy를 기준으로 체적을 구하였을 때 V_5Gy는 각각 87%, 49%, 96%로 나타났다. 이외의 시신경을 제외한 나머지(뇌줄기, 해마, 양측 안구)의 최대선량은 HTCB에서 가장 낮았다. 결 론: 토모테라피에서 Complete Block을 적용하였을 때 전체 뇌 조직의 선량 감소와 더불어 뇌에 포함된 양쪽 해마 등의 손상 위험 장기의 선량을 가장 최소화해 방사선 유도 뇌 손상의 발생과 그로 인한 신경인지 기능 감소 등에 대한 부작용의 확률을 줄일 수 있는 치료계획임을 확인하였다. 향후에는 총 두피 조사 이외에도 다양한 부위에 치료되는 고리 형태의 표적(Ring Target)에 대한 추가적인 연구를 진행하여 접선 조사에 대한 이점을 확립하게 된다면 치료계획 시 접선조사 극대화를 위해 Complete Block을 사용한 토모테라피를 적용함으로써 선량적으로 유용한 결과를 얻을 수 있을 것으로 사료된다.

• Clinical and Experimental Reproductive Medicine
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• 제31권1호
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• pp.19-27
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• 2004

Objective: This study was to examine the in vitro neural cell differentiation patterns of human embryonic stem (hES) cells following treatment of various neurotrophic factors [basic fibroblast growth factor (bFGF), retinoic acid (RA), brain derived neurotrophic factor (BDNF) and transforming growth factor (TGF)-$\alpha$], particulary in dopaminergic neuron formation. Methods: The hES cells were induced to differentiate by bFGF and RA. Group I) In bFGF induction method, embryoid bodies (EBs, for 4 days) derived from hES were plated onto gelatin dish, selected for 8 days in ITSFn medium and expanded at the presence of bFGF (10 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14 and 21 days. Group II) For RA induction, EBs were exposed of RA ($10^{-6}M$) for 4 days and allowed to differentiate in N2 medium for 7, 14 and 21 days. Group III) To examine the effects of additional neurotrophic factors, bFGF or RA induced cells were exposed to either BDNF (10 ng/ml) or TGF-$\alpha$ (10 ng/ml) during the 21 days of final differentiation. Neuron differentiation and dopamine secretion were examined by indirect immunocytochemistry and HPLC, respectively. Results: The bFGF or RA treated hES cells were resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with BDNF or TGF-$\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression of a dopaminergic neuron marker, compared to control (p<0.05). In contrast, no effect was observed on the rate of mature neuron (NF-200) or glutamic acid decarboxylase-positive neurons. Immunocytochemistry and HPLC analyses revealed the higher levels of TH expression (20.3%) and dopamine secretion (265.5 $\pm$ 62.8 pmol/mg) in bFGF and TGF-sequentially treated hES cells than those in $\alpha$ RA or BDNF treated hES cells. Conclusion: These results indicate that the generation of dopamine secretory neurons from in vitro differentiated hES cells can be improved by TGF-$\alpha$ addition in the bFGF induction protocol.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.77-77
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• 2003

Coculture of HSC with bone marrow-derived mesenchymal stem cells (BM-MSCs) is one of used methods to increase cell numbers before transplant to the patients. However, because of difficulties to purify HSCs after coculture with BM-MSCs, it needs to develop a method to overcome the problem. In the present study, we have examined whether a culture insert placed over a feeder layer might support the expansion of HSCs within the insert. $CD34^+/ $ cells isolated from the umbilical cord blood by using midiMACS were divided into three groups. A group of 1 $\times$ $10^5$ cells were grown on a culture insert without feeder layer (Direct). The same number of HSCs was directly cocultured with BM-MSCs (Contact). The third group was placed onto an insert below which BM-MSCs were grown (Insert). To distinguish feeder cells from HSCs, BM-MSCs was pre-labeled fluorescently with PKH26 and 1 $\times$ $10^5$ cells were seeded in the culture dishes. After culture for 13 days, the expansion factor (x) of HSCs that were grown without feeder layer (Direct) was $26.6 \pm 8.4.$ In contrast, the number of HSCs directly cocultured with feeder layer was 59.6 $\pm$ 0.5 and that of HSCs cultured onto an insert was $46.9 \pm 8.4.$ The percentage of BM-MSCs cells remained being fluorescent was $97.9 \pm 0.3%$ after culture. Immune-phenotypically large proportion of cultured cells were founded to be differentiated into myeloid/monocyte progenitor cells. The ability of BM-MSCs, fetal lung, cartilage and brain tissue cells to support ex vivo expansion of HSCs was also examined using the insert. After 11 days of coculture with each of these cells, the expansion factor of HSCs was 15.0, 39.0, 32.0 and 24.0, respectively. Based upon these observations, it is concluded that the coculture method using insert is very effective to support ex vivo expansion of HSCs and to eliminate the contamination of other cells used to coculture wth HSCs.

• Molecules and Cells
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• 제37권7호
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• pp.547-553
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• 2014

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

• Clinical and Experimental Reproductive Medicine
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• 제29권2호
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• pp.117-127
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• 2002

Objective: This study was to investigate the generation of the functional neuron derived from human embryonic stem (hES, MB03) cells on in vitro neural cell differentiation system. Methods: For neural progenitor cell formation derived from hES cells, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for $7{\sim}10$ days, 20 ng/ml of bFGF added N2 medium) from EB. And then finally for the differentiation into mature neuron, neural progenitor cells were cultured in i) N2 medium only (without bFGF), ii) N2 supplemented with 20 ng/ml platelet derived growth factor-bb (PDGF-bb) or iii) N2 supplemented with 5 ng/ml brain derived neurotrophic factor (BDNF) for 2 weeks. Identification of neural cell differentiation was carried out by immunocytochemistry using $\beta_{III}$-tubulin (1:250), MAP-2 (1:100) and GFAP (1:500). Also, generation of functional neuron was identified using anti-glutamate (Sigma, 1:1000), anti-GABA (Sigma, 1:1000), anti-serotonin (Sigma, 1:1000) and anti-tyrosine hydroxylase (Sigma, 1:1000). Results: In vitro neural cell differentiation, neurotrophic factors (PDGF and BDNF) treated cell groups were high expressed MAP-2 and GFAP than non-treated cell group. The highest expression pattern of MAP-2 and $\beta_{III}$-tubulin was indicated in BDNF treated group. Also, in the presence of PDGF-bb or BDNF, most of the neural cells derived from hES cells were differentiated into glutamate and GABA neuron in vitro. Furthermore, we confirmed that there were a few serotonin and tyrosine hydroxylase positive neuron in the same culture environment. Conclusion: This results suggested that the generation of functional neuron derived from hES cells was increased by addition of neurotrophic factors such as PDGF-bb or BDNF in b-FGF induced neural cell differentiation system and especially glutamate and GABA neurons were mainly produced in the system.