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1.  Dissociation between Neural Signatures of Stimulus and Choice in Population Activity of Human V1 during Perceptual Decision-Making 
The Journal of Neuroscience  2014;34(7):2725-2743.
Primary visual cortex (V1) forms the initial cortical representation of objects and events in our visual environment, and it distributes information about that representation to higher cortical areas within the visual hierarchy. Decades of work have established tight linkages between neural activity occurring in V1 and features comprising the retinal image, but it remains debatable how that activity relates to perceptual decisions. An actively debated question is the extent to which V1 responses determine, on a trial-by-trial basis, perceptual choices made by observers. By inspecting the population activity of V1 from human observers engaged in a difficult visual discrimination task, we tested one essential prediction of the deterministic view: choice-related activity, if it exists in V1, and stimulus-related activity should occur in the same neural ensemble of neurons at the same time. Our findings do not support this prediction: while cortical activity signifying the variability in choice behavior was indeed found in V1, that activity was dissociated from activity representing stimulus differences relevant to the task, being advanced in time and carried by a different neural ensemble. The spatiotemporal dynamics of population responses suggest that short-term priors, perhaps formed in higher cortical areas involved in perceptual inference, act to modulate V1 activity prior to stimulus onset without modifying subsequent activity that actually represents stimulus features within V1.
doi:10.1523/JNEUROSCI.1606-13.2014
PMCID: PMC3921435  PMID: 24523561
choice probability; decision-making; fMRI; visual perception; perceptual decision; V1
2.  Surgical Treatment of T1-2 Disc Herniation with T1 Radiculopathy: A Case Report with Review of the Literature 
Asian Spine Journal  2012;6(3):199-202.
The prevalence of intervertebral disc herniation (IDH) of the thoracic spine is rare compared to the cervical or lumbar spine. In particular, IDH of the upper thoracic spine is extremely rare. We report the case of T1-2 IDH and its treatment, with a literature review. A 37-year-old male patient visited our hospital due to radiating pain at the left upper extremity and weakness of grip power. In cervical spine magnetic resonance images, T1-2 disc space showed herniated disc material and compressed T1 root was identified. Laminoforaminotomy was performed with a posterior approach. The radiating pain and weakness of grip power improved immediately after the surgery. Of patients who show radiating pain or numbness at the medial aspect of forearm, or weakness of intrinsic muscle of hand, can be suspected to have T1 radiculopathy. A detailed physical examination and a radiologic evaluation including this area should be required for the T1 radiculopathy.
doi:10.4184/asj.2012.6.3.199
PMCID: PMC3429611  PMID: 22977700
Thoracic Vertebrae; Intervertebral Disc; Radiculopathy; Laminotomy
3.  Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease 
The Journal of Clinical Investigation  2011;121(6):2326-2335.
Parkinson disease (PD) involves the selective loss of midbrain dopamine (mDA) neurons and is a possible target disease for stem cell–based therapy. Human induced pluripotent stem cells (hiPSCs) are a potentially unlimited source of patient-specific cells for transplantation. However, it is critical to evaluate the safety of hiPSCs generated by different reprogramming methods. Here, we compared multiple hiPSC lines derived by virus- and protein-based reprogramming to human ES cells (hESCs). Neuronal precursor cells (NPCs) and dopamine (DA) neurons delivered from lentivirus-based hiPSCs exhibited residual expression of exogenous reprogramming genes, but those cells derived from retrovirus- and protein-based hiPSCs did not. Furthermore, NPCs derived from virus-based hiPSCs exhibited early senescence and apoptotic cell death during passaging, which was preceded by abrupt induction of p53. In contrast, NPCs derived from hESCs and protein-based hiPSCs were highly expandable without senescence. DA neurons derived from protein-based hiPSCs exhibited gene expression, physiological, and electrophysiological properties similar to those of mDA neurons. Transplantation of these cells into rats with striatal lesions, a model of PD, significantly rescued motor deficits. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of PD.
doi:10.1172/JCI45794
PMCID: PMC3104759  PMID: 21576821
4.  DISTINCT ENDOCANNABINOID CONTROL OF GABA RELEASE AT PERISOMATIC AND DENDRITIC SYNAPSES IN THE HIPPOCAMPUS 
Endocannabinoid mediated retrograde synaptic signaling is a key regulator of GABA release at synapses formed on the perisomatic region of pyramidal cells by basket cells that co-express the cannabinoid type 1 receptor (CB1R) and cholecystokinin (CCK). However, CB1R and CCK positive GABAergic terminals are present on pyramidal cell dendrites as well, but the principles of endocannabinoid control of GABA release in dendrites are not understood. We performed paired recordings from CCK positive perisomatically (basket cells) or dendritically projecting (Schaffer-collateral associated cells) interneurons and postsynaptic CA1 pyramidal cells to determine the properties of endocannabinoid signaling at GABAergic synapses along the somato-dendritic axis. Although several key elements of the currently known molecular machinery for endocannabinoid synthesis are thought be primarily localized in dendrites, our results revealed that the depolarization-induced suppression of inhibition (DSI), the endocannabinoid-mediated tonic inhibition of GABA release, and the metabotropic glutamate receptor activation induced, CB1R mediated depression of GABA release were all significantly less effective at dendritic compared to perisomatic synapses. In addition, low concentration of exogenous CB1 receptor agonist inhibited GABA release to a lesser extent at dendritic compared to perisomatic synapses, indicating that presynaptic differences are partly responsible for the differential control of GABA release by endocannabinoids in dendrites.
Taken together, these data demonstrate a novel domain-specific regulation of GABA release by endocannabinoid signaling in the hippocampus.
doi:10.1523/JNEUROSCI.6238-09.2010
PMCID: PMC2904437  PMID: 20534847
endocannabinoid; interneuron; GABA; inhibition
5.  Generation of Dopamine Neurons with Improved Cell Survival and Phenotype Maintenance Using a Degradation-Resistant Nurr1 Mutant 
Stem Cells (Dayton, Ohio)  2009;27(9):2238-2246.
Nurr1 is a transcription factor specific for the development and maintenance of the midbrain dopamine (DA) neurons. Exogenous Nurr1 in neural precursor (NP) cells induces the differentiation of DA neurons in vitro that are capable of reversing motor dysfunctions in a rodent model for Parkinson disease. The promise of this therapeutic approach, however, is unclear due to poor cell survival and phenotype loss of DA cells after transplantation. We herein demonstrate that Nurr1 proteins undergo ubiquitin-proteasome-system-mediated degradation in differentiating NP cells. The degradation process is activated by a direct Akt-mediated phosphorylation of Nurr1 proteins and can be prevented by abolishing the Akt-target sequence in Nurr1 (Nurr1Akt). Overexpression of Nurr1Akt in NP cells yielded DA neurons in which Nurr1 protein levels were maintained for prolonged periods. The sustained Nurr1 expression endowed the Nurr1Akt-induced DA neurons with resistance to toxic stimuli, enhanced survival, and sustained DA phenotypes in vitro and in vivo after transplantation.
doi:10.1002/stem.146
PMCID: PMC2816355  PMID: 19522012
Nurr1; Dopamine neuron; Ubiquitin-proteasome-system; Cell survival; Midbrain; Akt
6.  Genistein Promotes Endothelial Colony-Forming Cell (ECFC) Bioactivities and Cardiac Regeneration in Myocardial Infarction 
PLoS ONE  2014;9(5):e96155.
Although stem cell-mediated treatment of ischemic diseases offers significant therapeutic promise, the limitation in the therapeutic efficacy of transplanted stem cells in vivo because of poor engraftment remains a challenge. Several strategies aimed at improving survival and engraftment of stem cells in the ischemic myocardium have been developed, such as cell transplantation in combination with growth factor delivery, genetic modification of stem cells, and/or cell therapy using scaffolds. To improve therapeutic efficacy, we investigated the effects of genistein on the engraftment of transplanted ECFCs in an acute myocardial ischemia model. Results: We found that genistein treatment enhanced ECFCs' migration and proliferation, which was accompanied by increases in the expression of ILK, α-parvin, F-actin, and phospholylation of ERK 1/2 signaling. Transplantation of genistein-stimulates ECFCs (GS-ECFCs) into myocardial ischemic sites in vivo induced cellular proliferation and secretion of angiogenic cytokines at the ischemic sites and thereby enhanced neovascularization and decreased myocardial fibrosis as well as improved cardiac function, as shown by echocardiography. Taken together, these data suggest that pretreatment of ECFCs with genistein prior to transplantation can improve the regenerative potential in ischemic tissues, providing a novel strategy in adult stem cell therapy for ischemic diseases.
doi:10.1371/journal.pone.0096155
PMCID: PMC4022670  PMID: 24830850
7.  Impact of Treatment With Statins on Prostate-Specific Antigen and Prostate Volume in Patients With Benign Prostatic Hyperplasia 
Korean Journal of Urology  2013;54(11):750-755.
Purpose
We investigated the impact on prostate-specific antigen (PSA) and prostate volume (PV) of statin medication for 1 year in patients with benign prostatic hyperplasia (BPH).
Materials and Methods
We retrospectively investigated 791 patients in whom BPH was diagnosed. For analysis, the patients were divided into four groups according to their medications: group A, α-blocker; group B, α-blocker+statin; group C, α-blocker+dutasteride; group D, α-blockers+statin+dutasteride. To investigate changes in serum PSA, PV, and total cholesterol, we analyzed the data at the time of initial treatment and after 1 year of medication.
Results
After 1 year, group A showed a 1.3% increase in PSA and a 1.0% increase in PV. Group B showed a 4.3% decrease in PSA and a 1.8% decrease in PV. The difference in PV reduction between groups A and B was statistically significant (p<0.001). Group C showed a 49.1% reduction in PSA and a 22.9% reduction in PV. Group D showed a 51.6% reduction in PSA and a 24.5% reduction in PV. The difference in PV reduction between groups C and D was not statistically significant (p=0.762). By use of a multivariate logistic regression model, we found that the probability of PV reduction after 1 year was more than 14.8 times in statin users than in statin nonusers (95% confidence interval, 5.8% to 37.6%; p<0.001).
Conclusions
Statin administration reduced PSA and PV in BPH patients. This finding may imply the improvement of lower urinary tract symptoms and prevention of cardiovascular disease and chemoprevention of prostate cancer with statin treatment.
doi:10.4111/kju.2013.54.11.750
PMCID: PMC3830967  PMID: 24255756
Chemoprevention; Dutasteride; Prostate; Prostate-specific antigen; Statins
8.  Individual differences in the perception of biological motion and fragmented figures are not correlated 
We live in a cluttered, dynamic visual environment that poses a challenge for the visual system: for objects, including those that move about, to be perceived, information specifying those objects must be integrated over space and over time. Does a single, omnibus mechanism perform this grouping operation, or does grouping depend on separate processes specialized for different feature aspects of the object? To address this question, we tested a large group of healthy young adults on their abilities to perceive static fragmented figures embedded in noise and to perceive dynamic point-light biological motion figures embedded in dynamic noise. There were indeed substantial individual differences in performance on both tasks, but none of the statistical tests we applied to this data set uncovered a significant correlation between those performance measures. These results suggest that the two tasks, despite their superficial similarity, require different segmentation and grouping processes that are largely unrelated to one another. Whether those processes are embodied in distinct neural mechanisms remains an open question.
doi:10.3389/fpsyg.2013.00795
PMCID: PMC3812695  PMID: 24198799
perceptual grouping; biological motion; fragmented figures; individual differences
9.  Prevalence and Geographic Distribution of Herniated Intervertebral Disc in Korean 19-Year-Old Male from 2008 to 2009: A Study Based on Korean Conscription -National and Geographic Prevalence of Herniated Intervertebral Disc in Korean 19YO Male- 
Yonsei Medical Journal  2013;54(5):1098-1103.
Purpose
This study was to determine the prevalence of herniated intervertebral disc (HIVD) among Korean 19-year-old male in a large national sample and to compare the prevalence across geographic regions based on the data of conscription.
Materials and Methods
We analyzed the conscription data of 615508 cases who were 19-year-old male, given an examination for conscription at nationwide Korean Military Manpower Administration from January 2008 to December 2009. Prevalence was determined by dividing the number of cases by the number of persons enrolled for 2 years. The analyses included of a cross-tabulations and nonparametric chi-square to compare the prevalence according to geographic region, disc severity, and conscription year.
Results
The prevalence of HIVD among 19-year-old male was 0.47%. Seoul had the highest prevalence of HIVD (total HIVD was 0.60%, and severe HIVD was 0.44%). The prevalence of HIVD was lower in Jeollabuk-do and Jeollanam-do (total HIVD was 0.25-0.27%, and severe HIVD was 0.16-0.17%). Annual prevalence of HIVD was slightly decreased in 2009, but geographic distribution annually was not different.
Conclusion
In Korean 19-year-old male, the national prevalence of adolescent HIVD was 0.60%, but different geographic distribution was observed. It is quite possible that secondary contributing factor(s) interfere with the different geographic prevalence of HIVD.
doi:10.3349/ymj.2013.54.5.1098
PMCID: PMC3743194  PMID: 23918557
Herniated intervertebral disc; adolescent; prevalence; conscription
10.  The Relationship Between Muscle Fatigue and Balance in the Elderly 
Annals of Rehabilitation Medicine  2013;37(3):389-395.
Objective
To investigate the effect of gastrocnemius muscle fatigue on postural control ability in elderly people.
Methods
Twenty-four healthy elderly people participated in this study. The postural control ability of single leg standing was evaluated with Health Improvement & Management System (HIMS) posturography before and after fatiguing exercises. After evaluating initial postural control ability, the maximal voluntary contraction (MVC) of ankle plantarflexion was assessed using a surface electromyogram from the medial belly of the gastrocnemius muscle. After a 5-minute resting period, subjects began submaximal isometric ankle plantarflexion (40% MVC) until 40% of MVC was dropped below 95% for 5 seconds, or subject couldn't continue working out due to muscle fatigue. And postural control ability was assessed after fatiguing exercise. The mean deviation of center of pressure (COP), length of COP movement, occupied area of COP were measured, and analyzed by paired t-test.
Results
Mediolateral deviation, length of COP movement, and area of COP occupied were increased after fatiguing exercise of the gastrocnemius muscle. Anteroposterior deviation and length of COP movement were also increased, but had low statistical significance.
Conclusion
These findings suggest that the gastrocnemius muscle fatigue affects mediolateral stability and accuracy during single leg standing in elderly people. Therefore muscle endurance training is necessary to prevent falls in elderly people.
doi:10.5535/arm.2013.37.3.389
PMCID: PMC3713296  PMID: 23869337
Balance; Posture; Elderly; Fatigue; Ankle
11.  New dimensions of interneuronal specialization unmasked by principal cell heterogeneity 
Trends in Neurosciences  2011;35(3):175-184.
While the diversity of neocortical and hippocampal GABAergic interneurons is recognized in terms of their anatomical, molecular, and functional properties, principal cells are usually assumed to constitute homogenous populations. However, even within a single layer, subpopulations of principal cells can often be differentiated by their distinct long-range projection targets. Such subpopulations of principal cells can have different local connection properties and excitatory inputs, forming subnetworks that may serve as separate information-processing channels. Interestingly, as reviewed here, recent evidence has revealed specific instances where interneuron cell types selectively innervated distinct subpopulations of principal cells, targeting only those with particular long-distance projection targets. This organization represents a novel form of interneuron specialization, providing interneurons with the potential to selectively regulate specific information-processing streams.
doi:10.1016/j.tins.2011.10.005
PMCID: PMC3294038  PMID: 22119146
12.  Identification of mouse colony-forming endothelial progenitor cells for postnatal neovascularization: a novel insight highlighted by new mouse colony-forming assay 
Introduction
Endothelial progenitor cells (EPCs) play a critical role in restoration of ischemic diseases. However, the actual status of EPC development and the mechanisms of EPC dysfunctions in patients with various ischemic diseases remain unknown.
Methods
To investigate the detailed function of EPCs in experimental murine models, we have established an EPC colony forming assay (EPC-CFA) in murine EPCs. The abilities of murine EPCs in differentiation, adhesive capacity, proliferative potency, and transplantation in vitro and in vivo were then examined.
Results
Peripheral blood mononuclear cells (PB-MNCs), bone marrow mononuclear cells (BM-MNCs) or bone marrow c-Kit+/Sca-1+ lineage negative (BM-KSL) cells differentiated into two types of EPC colony forming units (EPC-CFUs), large sized EPC (large-EPC)-CFUs and small sized EPC (small-EPC)-CFUs. Gene expression analysis demonstrated that both EPC-CFU-derived cells expressed eNOS, Flk-1 and VE-cadherin, markers of endothelial cells (ECs), although the small-EPCs derived from small-EPC-CFU were higher in number and showed more immature features (higher population of KSL cells). Functionally, the large-EPCs derived from large-EPC-CFU had higher adhesive capacity but lower proliferative potency than small-EPCs, showing improved tubular forming capacity and incorporation potency into primary EC-derived tube formation. Importantly, hindlimb ischemia increased the frequencies of large-EPC-CFUs differentiated from PB-MNCs and bone marrow. Actually, transplantation of large-EPCs into ischemic hindlimb enhanced neovascularization in hindlimb ischemia model, although small-EPCs or murine ECs did not, suggesting that large-EPC-CFUs might play an important role in restoration of ischemic diseases.
Conclusions
We demonstrated, using a murine ischemia model, that the EPC-CFA could be a useful way to investigate the differentiation levels of murine EPCs, further providing a crucial clue that large-EPC-CFU status may be more functional or effective EPCs to promote neovascularization.
doi:10.1186/scrt168
PMCID: PMC3706928  PMID: 23448126
15.  Risk factors affecting seroconversion after influenza A/H1N1 vaccination in hemodialysis patients 
BMC Nephrology  2012;13:165.
Abstracts
Background
Hemodialysis (HD) patients have multiple causes of immune dysfunction and poor immune response to influenza vaccination. We investigated the antibody response rate to a pandemic H1N1/2009 influenza vaccination and clinical parameters influencing the induction of antibody responses in HD patients.
Methods
A total of 114 HD patients were vaccinated with a monovalent adjuvanted H1N1 inactivated influenza vaccine. Titers of neutralizing antibodies were evaluated by hemagglutination inhibition (HI) assay at pre- and 4 weeks after vaccination. Seroconversion was defined as either a pre-vaccination HI titer < 1:10 and a post vaccination HI titer > 1:40 or a pre-vaccination HI titer ≥ 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seventeen out of 114 HD patients (14.9%) tested positive for antibodies against influenza A/H1N1/2009 before vaccination. The remaining 97 baseline sero-negative patients were included in the analysis.
Results
Only 30 (30.9%) HD patients had seroconversion 4 weeks after vaccination. The elderly patients, those over 65 years of age, showed significantly lower seroconversion rate compared to younger HD patients (20.5% vs. 39.6%, p = 0.042). Furthermore, patients with hemoglobin values less than 10 g/dL had a significantly lower seroconversion rate compared to those with higher hemoglobin values (20.0 vs. 38.6%, p = 0.049). By multivariate logistic regression analysis, only age ≥65 years (OR = 0.336, 95% confidence interval (CI) 0.116-0.971, p = 0.044) and hemoglobin levels <10 g/dL (OR = 0.315, 95% CI 0.106-0.932, p = 0.037) were independently associated with seroconversion after vaccination.
Conclusions
Our data show that HD patients, especially who are elderly with low hemoglobin levels, are at increased risk for lower seroconversion rate after influenza A/H1N1 vaccination. Further studies are needed to improve the efficacy of vaccination in these high risk patients.
doi:10.1186/1471-2369-13-165
PMCID: PMC3560184  PMID: 23206898
Hemodialysis; Pandemic H1N1/2009 influenza; Vaccine; Seroconversion
16.  Cervical Pedicle Screw Insertion Using the Technique with Direct Exposure of the Pedicle by Laminoforaminotomy 
Objective
To present the accuracy and safety of cervical pedicle screw insertion using the technique with direct exposure of the pedicle by laminoforaminotomy.
Methods
We retrospectively reviewed 12 consecutive patients. A total of 104 subaxial cervical pedicle screws in 12 patients had been inserted. We also assessed the clinical and radiological outcomes and analyzed the direction and grade of pedicle perforation (grade 0: no perforation, 1: <25%, 2: 20% to 50%, 3: >50% of screw diameter) on the postoperative vascular-enhanced computed tomography scans. Grade 2 and 3 were considered as incorrect position.
Results
The correct position was found in 95 screws (91.3%); grade 0-75 screws, grade 1-20 screws and the incorrect position in 9 screws (8.7%); grade 2-6 screws, grade 3-3 screws. There was no neurovascular complication related with cervical pedicle screw insertion.
Conclusion
This technique (technique with direct exposure of the pedicle by laminoforaminotomy) could be considered relatively safe and easy method to insert cervical pedicle screw.
doi:10.3340/jkns.2012.52.5.459
PMCID: PMC3539080  PMID: 23323166
Cervical pedicle screw; Laminoforaminotomy; Pedicle perforation
17.  Wilms' Tumor in a Horseshoe Kidney 
Korean Journal of Urology  2012;53(8):577-580.
The incidence of horseshoe kidney is about 1 in 400 cases. The presence of Wilms' tumor with a horseshoe kidney is unusual, and the occurrence of Wilms' tumor in a horseshoe kidney is estimated at 0.4 to 0.9% of all Wilms' tumors. We report the case of a 5-year-old boy who presented with a stage IV Wilms' tumor in a horseshoe kidney. The patient was treated with preoperative chemotherapy followed by surgical resection and adjuvant chemotherapy. This case illustrates the role of preoperative chemotherapy for preserving renal function and aims to highlight the multimodality treatment of Wilms' tumor.
doi:10.4111/kju.2012.53.8.577
PMCID: PMC3427845  PMID: 22950005
Adjuvant chemotherapy; Neoadjuvant therapy; Wilms tumor
18.  Tumor Establishment Features of Orthotopic Murine Bladder Cancer Models 
Korean Journal of Urology  2012;53(6):396-400.
Purpose
Animal tumor models are important for the evaluation of novel therapeutic modalities. Since the initial report of an orthotopic bladder tumor model, several modifications have been proposed to improve the tumor take rate. Here we compared the HCl-pretreated and electrocauterization-pretreated orthotopic murine bladder tumor models.
Materials and Methods
MBT-2 murine bladder cancer cells were transurethrally implanted in the bladder of syngeneic C3H/He mice. The mice were divided into three groups according to pretreatment methods (electrocautery, HCl, and control group) and were subjected to pretreatment before instillation of MBT-2 tumor cells into the bladder. Mice were sacrificed on day 21, and bladders were harvested, weighed, and examined histopathologically.
Results
The tumor take rate of the control, electrocautery, and HCl groups was 0%, 54%, and 100%, respectively. The tumor take rate of the HCl group was significantly higher than that of the control group (p<0.01) and the electrocautery group (p=0.01). Pathologic reports revealed that all established bladder tumors were high-grade papillary urothelial carcinomas.
Conclusions
The HCl pretreatment model was a preferable murine bladder tumor model for evaluating further therapeutic interventions.
doi:10.4111/kju.2012.53.6.396
PMCID: PMC3382688  PMID: 22741047
Animal models; Intravesical administration; Urinary bladder neoplasms
19.  Ivy and neurogliaform interneurons are a major target of μ opioid receptor modulation 
Mu opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous, but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABAB response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Further, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR-activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking PV basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR-activation. Together these findings identify a major, previously unrecognized, target of μOR-modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications.
doi:10.1523/JNEUROSCI.2269-11.2011
PMCID: PMC3226788  PMID: 22016519
20.  Phloroglucinol Inhibits the Bioactivities of Endothelial Progenitor Cells and Suppresses Tumor Angiogenesis in LLC-Tumor-Bearing Mice 
PLoS ONE  2012;7(4):e33618.
Background
There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis.
Methodology/Principal Findings
This is the first report on phloroglucinol's ability to potentially inhibit the functional bioactivities of endothelial progenitor cells (EPCs) and thereby attenuate tumor growth and angiogenesis in the Lewis lung carcinoma (LLC)-tumor-bearing mouse model. Although Phloroglucinol did not affect their cell toxicity, it specifically inhibited vascular endothelial growth factor (VEGF) dependent migration and capillary-like tube formation of EPCs. Our matrigel plug assay clearly indicated that orally injected phloroglucinol effectively disrupts VEGF-induced neovessel formation. Moreover, we demonstrated that when phloroglucinol is orally administered, it significantly inhibits tumor growth and angiogenesis as well as CD45−/CD34+ progenitor mobilization into peripheral blood in vivo in the LLC-tumor-bearing mouse model.
Conclusions/Significance
These results suggest a novel role for phloroglucinol: Phloroglucinol might be a modulator of circulating EPC bioactivities, eventually suppressing tumorigenesis. Therefore, phloroglucinol might be a candidate compound for biosafe drugs that target tumor angiogenesis.
doi:10.1371/journal.pone.0033618
PMCID: PMC3322124  PMID: 22496756
21.  Is It Real False Negative Finding in Motor Evoked Potential Monitoring during Corrective Surgery of Ankylosing Spondylitis? A Case Report 
Asian Spine Journal  2012;6(1):50-54.
We performed L1 posterior vertebral columnar resection and posterior correction for Andersson's lesion and thoracolumbar kyphosis in an ankylosing spondylitis patient during motor evoked potential (MEP) monitoring. We checked MEP intra-operatively, whenever a dangerous procedure for neural elements was performed, and no abnormal findings were seen during surgery. After the operation, we examined neurologic function in the recovery room; the patient showed a progressive neurologic deficit and no response to MEP. After emergency neural exploration and decompression surgery, the neurologic deficit was recovered. We questioned whether to acknowledge the results of this case as a false negative. We think the possible reason for this result may be delayed development of paralysis. So, we recommend that MEP monitoring should be performed not only after important operative steps but also after all steps, including skin suturing, for final confirmation.
doi:10.4184/asj.2012.6.1.50
PMCID: PMC3302915  PMID: 22439088
Spine operation; Deformity correction; Motor evoked potential; Delayed paraplegia
22.  Phloroglucinol Inhibits the in vitro Differentiation Potential of CD34 Positive Cells into Endothelial Progenitor Cells 
Biomolecules & Therapeutics  2012;20(2):158-164.
Inhibiting the bioactivities of circulating endothelial progenitor cells (EPCs) results in significant inhibition of neovessel formation during tumor angiogenesis. To investigate the potential effect of phloroglucinol as an EPC inhibitor, we performed several in vitro functional assays using CD34+ cells isolated from human umbilical cord blood (HUCB). Although a high treatment dose of phloroglucinol did not show any cell toxicity, it specifically induced the cell death of EPCs under serum free conditions through apoptosis. In the EPC colony-forming assay (EPC-CFA), we observed a significant decreased in the small EPC-CFUs for the phloroglucinol group, implying that phloroglucinol inhibited the early stage of EPC commitment. In addition, in the in vitro expansion assay using CD34+ cells, treatment with phloroglucinol was shown to inhibit endothelial lineage commitment, as demonstrated by the decrease in endothelial surface markers of EPCs including CD34+, CD34+/CD133+, CD34+/CD31+ and CD34+/CXCR4+. This is the first report to demonstrate that phloroglucinol can inhibit the functional bioactivities of EPCs, indicating that phloroglucinol may be used as an EPC inhibitor in the development of biosafe anti-tumor drugs that target tumor angiogenesis.
doi:10.4062/biomolther.2012.20.2.158
PMCID: PMC3792212  PMID: 24116289
Endothelial progenitor cell; Tumor angiogenesis; Phloroglucinol; Colony forming assay
23.  Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage 
PLoS ONE  2012;7(2):e25936.
Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.
doi:10.1371/journal.pone.0025936
PMCID: PMC3277599  PMID: 22347993
24.  Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle 
We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid depolarizing and repolarizing phases, and (2) Type II pulse had a rapid depolarizing phase and a gradually slowing repolarizing phase.
doi:10.1155/2012/269397
PMCID: PMC3272967  PMID: 22319544
25.  Patterned Si thin film electrodes for enhancing structural stability 
A patterned film (electrode) with lozenge-shaped Si tiles could be successfully fabricated by masking with an expanded metal foil during film deposition. Its electrochemical properties and structural stability during the charge-discharge process were examined and compared with those of a continuous (conventional) film electrode. The patterned electrode exhibited a remarkably improved cycleability (75% capacity retention after 120 cycles) and an enhanced structural stability compared to the continuous electrode. The good electrochemical performance of the patterned electrode was attributed to the space between Si tiles that acted as a buffer against the volume change of the Si electrode.
doi:10.1186/1556-276X-7-20
PMCID: PMC3274471  PMID: 22221620
patterned electrode; silicon film; stress; anode

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