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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.
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.
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.
PMCID: PMC3104759  PMID: 21576821
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.
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.
PMCID: PMC2816355  PMID: 19522012
Nurr1; Dopamine neuron; Ubiquitin-proteasome-system; Cell survival; Midbrain; Akt
6.  Surgical Correction in Patients with Lumbar Degenerative Kyphosis Who Had Low Bone Mineral Density: An Analysis of 40 Patients with a Minimum Follow-Up of Two Years 
Asian Spine Journal  2015;9(1):65-74.
Study Design
Retrospective study.
To investigate influence of bone mineral density (BMD) on the surgical correction of lumbar degenerative kyphosis (LDK).
Overview of Literature
No studies so far have reported the influence of BMD on the surgical correction of LDK.
Forty LDK patients with more than 2 years follow-up were studied. Pelvic incidence (PI), pelvic tilt, sacral slope, sagittal vertical axis (SVA), lumbar lordosis (LL), and thoracic kyphosis were measured preoperatively, immediate postoperatively and at final follow-up. Adverse outcomes: proximal adjacent fractures, sagittal decompensation, pseudoarthrosis, and cage subsidence were documented.
There were 37 females and 3 males. Average age was 65.1±4.5 years and mean follow-up was 34.2±16.7 months. 42.5% were Takemitsu type 3 curves, 27.5% type 2, 20.0% type 4 and 10.0% type 1. 37.5% had osteopenia, 40.0% osteoporosis and 22.5% had severe osteoporosis. SVA improved from 237.0±96.7 mm preoperatively to 45.3±41.8 mm postoperatively (p=0.000). LL improved from 10.5°±14.7° to -40.6°±10.9° postoperatively (p=0.000). At final follow-up SVA deteriorated to 89.8±72.2 mm and LL to 34.7°±15.8° (p=0.000). The association between late sagittal decompensation, pseudoarthrosis, or proximal adjacent fractures and osteoporosis was insignificant. The difference between immediate postoperative LL and PI (PIDiff) had a significant association with sagittal decompensation and pseudoarthrosis.
Osteoporosis did not influence the degree of correction, late sagittal decompensation, proximal adjacent fractures, and pseudoarthrosis in LDK. PIDiff had a significant association with sagittal decompensation and pseudoarthrosis.
PMCID: PMC4330221
Lumbar degenerative kyphosis; Bone mineral density; Surgery; Outcome; Osteoporosis
7.  Transcriptional Profiles of Imprinted Genes in Human Embryonic Stem Cells During In vitro Differentiation 
Background and Objectives:
Genomic imprinting is an inheritance phenomenon by which a subset of genes are expressed from one allele of two homologous chromosomes in a parent of origin-specific manner. Even though fine-tuned regulation of genomic imprinting process is essential for normal development, no other means are available to study genomic imprinting in human during embryonic development. In relation with this bottleneck, differentiation of human embryonic stem cells (hESCs) into specialized lineages may be considered as an alternative to mimic human development.
Methods and Results:
In this study, hESCs were differentiated into three lineage cell types to analyze temporal and spatial expression of imprinted genes. Of 19 imprinted genes examined, 15 imprinted genes showed similar transcriptional level among two hESC lines and two human induced pluripotent stem cell (hiPSC) lines. Expressional patterns of most imprinted genes were varied in progenitors and fully differentiated cells which were derived from hESCs. Also, no consistence was observed in the expression pattern of imprinted genes within an imprinting domain during in vitro differentiation of hESCs into three lineage cell types.
Transcriptional expression of imprinted genes is regulated in a cell type- specific manner in hESCs during in vitro differentiation.
PMCID: PMC4249893  PMID: 25473448
Human embryonic stem cells; Genomic imprinting; In vitro differentiation; Transcriptional expression
8.  Identifying the initiating events of anti-Listeria responses using mice with conditional loss of IFNγ receptor subunit 1 (IFNGR1) 
Journal of immunology (Baltimore, Md. : 1950)  2013;191(8):10.4049/jimmunol.1300910.
Whereas IFNγ is required for resolution of Listeria monocytogenes infection, the identities of the IFNγ responsive cells that initiate the process remain unclear. We addressed this question using novel mice with conditional loss of the IFNγ receptor (IFNGR1). Itgax-cre+Ifngr1f/f mice with selective IFNγ unresponsiveness in CD8α+ dendritic cells displayed increased susceptibility to infection. This phenotype was due to the inability of IFNγ unresponsive CD8α+ DCs to produce the initial burst of IL-12 induced by IFNγ from TNFα-activated NK/NKT cells. The defect in early IL-12 production resulted in increased IL-4 production that established a myeloid cell environment favoring Listeria growth. Neutralization of IL-4 restored Listeria resistance in Itgax-cre+Ifngr1f/f mice. We also found that Itgax-cre+Ifngr1f/f mice survived infection with low dose Listeria due to a second wave of IL-12 produced by Ly6Chi monocytes. Thus, an IFNγ-driven cascade involving CD8α+ DCs and NK/NKT cells induces the rapid production of IL-12 that initiates the anti-Listeria response.
PMCID: PMC3874833  PMID: 24048899
9.  Cross Talk with Hematopoietic Cells Regulates the Endothelial Progenitor Cell Differentiation of CD34 Positive Cells 
PLoS ONE  2014;9(8):e106310.
Despite the crucial role of endothelial progenitor cells (EPCs) in vascular regeneration, the specific interactions between EPCs and hematopoietic cells remain unclear.
In EPC colony forming assays, we first demonstrated that the formation of EPC colonies was drastically increased in the coculture of CD34+ and CD34− cells, and determined the optimal concentrations of CD34+ cells and CD34− cells for spindle-shaped EPC differentiation.
Functionally, the coculture of CD34+ and CD34− cells resulted in a significant enhancement of adhesion, tube formation, and migration capacity compared with culture of CD34+ cells alone. Furthermore, blood flow recovery and capillary formation were remarkably increased by the coculture of CD34+ and CD34− cells in a murine hind-limb ischemia model. To elucidate further the role of hematopoietic cells in EPC differentiation, we isolated different populations of hematopoietic cells. T lymphocytes (CD3+) markedly accelerated the early EPC status of CD34+ cells, while macrophages (CD11b+) or megakaryocytes (CD41+) specifically promoted large EPC colonies.
Our results suggest that specific populations of hematopoietic cells play a role in the EPC differentiation of CD34+ cells, a finding that may aid in the development of a novel cell therapy strategy to overcome the quantitative and qualitative limitations of EPC therapy.
PMCID: PMC4148437  PMID: 25166961
10.  Toward Integrated Molecular Diagnostic System (iMDx): Principles and Applications 
Integrated molecular diagnostic systems (iMDx), which are automated, sensitive, specific, user-friendly, robust, rapid, easy-to-use, and portable, can revolutionize future medicine. This review will first focus on the components of sample extraction, preservation, and filtration necessary for all point-of-care devices to include for practical use. Subsequently, we will look for low-powered and precise methods for both sample amplification and signal transduction, going in-depth to the details behind their principles. The final field of total device integration and its application to the clinical field will also be addressed to discuss the practicality for future patient care. We envision that microfluidic systems hold the potential to breakthrough the number of problems brought into the field of medical diagnosis today.
PMCID: PMC4141683  PMID: 24759281
Diagnostics; integration; microfluidics; point-of-care (POC)
11.  Doxycycline Enhances Survival and Self-Renewal of Human Pluripotent Stem Cells 
Stem Cell Reports  2014;3(2):353-364.
We here report that doxycycline, an antibacterial agent, exerts dramatic effects on human embryonic stem and induced pluripotent stem cells (hESC/iPSCs) survival and self-renewal. The survival-promoting effect was also manifest in cultures of neural stem cells (NSCs) derived from hESC/iPSCs. These doxycycline effects are not associated with its antibacterial action, but mediated by direct activation of a PI3K-AKT intracellular signal. These findings indicate doxycycline as a useful supplement for stem cell cultures, facilitating their growth and maintenance.
•Doxycycline enhances human pluripotent ESC/iPSC survival and self-renewal•Doxycycline-mediated survival effects are also shown in human neural stem cell (NSC)•Doxycycline effects are not associated with its antibacterial action•The doxycycline actions are mediated by direct activation of a PI3K-Akt signaling
In this article, Lee and colleagues show that doxycycline, an antibacterial agent, can be used as a useful culture supplement for facilitating cell survival and self-renewal of human embryonic stem and induced pluripotent stem cells (hESC/iPSCs). These doxycycline effects are not associated with its antibacterial action but mediated by direct activation of a PI3K-Akt intracellular signal.
PMCID: PMC4175555  PMID: 25254347
12.  Movement Type Prediction before Its Onset Using Signals from Prefrontal Area: An Electrocorticography Study 
BioMed Research International  2014;2014:783203.
Power changes in specific frequency bands are typical brain responses during motor planning or preparation. Many studies have demonstrated that, in addition to the premotor, supplementary motor, and primary sensorimotor areas, the prefrontal area contributes to generating such responses. However, most brain-computer interface (BCI) studies have focused on the primary sensorimotor area and have estimated movements using postonset period brain signals. Our aim was to determine whether the prefrontal area could contribute to the prediction of voluntary movement types before movement onset. In our study, electrocorticography (ECoG) was recorded from six epilepsy patients while performing two self-paced tasks: hand grasping and elbow flexion. The prefrontal area was sufficient to allow classification of different movements through the area's premovement signals (−2.0 s to 0 s) in four subjects. The most pronounced power difference frequency band was the beta band (13–30 Hz). The movement prediction rate during single trial estimation averaged 74% across the six subjects. Our results suggest that premovement signals in the prefrontal area are useful in distinguishing different movement tasks and that the beta band is the most informative for prediction of movement type before movement onset.
PMCID: PMC4122137  PMID: 25126578
13.  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.
PMCID: PMC4022670  PMID: 24830850
14.  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.
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.
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).
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.
PMCID: PMC3830967  PMID: 24255756
Chemoprevention; Dutasteride; Prostate; Prostate-specific antigen; Statins
15.  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.
PMCID: PMC3812695  PMID: 24198799
perceptual grouping; biological motion; fragmented figures; individual differences
16.  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.
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.
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.
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.
PMCID: PMC3743194  PMID: 23918557
Herniated intervertebral disc; adolescent; prevalence; conscription
17.  The Relationship Between Muscle Fatigue and Balance in the Elderly 
Annals of Rehabilitation Medicine  2013;37(3):389-395.
To investigate the effect of gastrocnemius muscle fatigue on postural control ability in elderly people.
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.
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.
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.
PMCID: PMC3713296  PMID: 23869337
Balance; Posture; Elderly; Fatigue; Ankle
18.  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.
PMCID: PMC3294038  PMID: 22119146
19.  Identification of mouse colony-forming endothelial progenitor cells for postnatal neovascularization: a novel insight highlighted by new mouse colony-forming assay 
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.
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.
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.
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.
PMCID: PMC3706928  PMID: 23448126
22.  Risk factors affecting seroconversion after influenza A/H1N1 vaccination in hemodialysis patients 
BMC Nephrology  2012;13:165.
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.
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.
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.
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.
PMCID: PMC3560184  PMID: 23206898
Hemodialysis; Pandemic H1N1/2009 influenza; Vaccine; Seroconversion
23.  Cervical Pedicle Screw Insertion Using the Technique with Direct Exposure of the Pedicle by Laminoforaminotomy 
To present the accuracy and safety of cervical pedicle screw insertion using the technique with direct exposure of the pedicle by laminoforaminotomy.
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.
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.
This technique (technique with direct exposure of the pedicle by laminoforaminotomy) could be considered relatively safe and easy method to insert cervical pedicle screw.
PMCID: PMC3539080  PMID: 23323166
Cervical pedicle screw; Laminoforaminotomy; Pedicle perforation
24.  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.
PMCID: PMC3427845  PMID: 22950005
Adjuvant chemotherapy; Neoadjuvant therapy; Wilms tumor
25.  Tumor Establishment Features of Orthotopic Murine Bladder Cancer Models 
Korean Journal of Urology  2012;53(6):396-400.
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.
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.
The HCl pretreatment model was a preferable murine bladder tumor model for evaluating further therapeutic interventions.
PMCID: PMC3382688  PMID: 22741047
Animal models; Intravesical administration; Urinary bladder neoplasms

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