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1.  Concomitant Occurrence of Cervical Myelopathy, Cerebral Infarction, and Peripheral Neuropathy in Systemic Lupus Erythematosus: A Case Report 
Annals of Rehabilitation Medicine  2014;38(2):263-268.
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterized by multiorgan involvement with diverse clinical presentations. Central nervous system involvement in neuropsychiatric syndromes of SLE (NPSLE), such as cerebrovascular disease and myelopathy, is a major cause of morbidity and mortality in SLE patients. The concomitant occurrence of myelopathy, cerebrovascular disease, and peripheral neuropathy in a patient with SLE has not yet been reported. We report on a 41-year-old woman with SLE who showed motor and sensory impairment with urinary retention and was diagnosed with cervical myelopathy and acute cerebral infarction by spine and brain magnetic resonance imaging and peripheral neuropathy by electrodiagnostic examination. Even though pathogenesis of NPSLE is not well elucidated, we assume that increased antibodies of anti-double stranded DNA (anti-dsDNA), presence of lupus anticoagulant and hypertension are risk factors that have caused neuropsychiatric lupus in this patient.
PMCID: PMC4026614  PMID: 24855622
Systemic lupus erythematosus; Myelopathy; Cerebral infarction
2.  The effects of attention on age-related relational memory deficits: Evidence from a novel attentional manipulation 
Psychology and aging  2011;26(3):678-688.
Healthy aging is often accompanied by episodic memory decline. Prior studies have consistently demonstrated that older adults show disproportionate deficits in relational memory (RM) relative to item memory (IM). Despite rich evidence of an age-related RM deficit, the source of this deficit remains unspecified. One of the most widely investigated factors of age-related RM impairment is a reduction in attentional resources. However, no prior studies have demonstrated that reduced attentional resources are the critical source of age-related RM deficits. Here, we utilized qualitatively different attention tasks, and tested whether reduced attention for relational processing underlies the RM deficit observed in aging. In Experiment 1, we imposed either item-detection or relation-detection attention tasks on young adults during episodic memory encoding, and found that only the concurrent attention task involving relational processing disproportionately impaired RM performance in young adults. Moreover, by ruling out the possible confound of task-difficulty on the disproportionate RM impairment, we further demonstrated that reduced relational attention is a key factor for the age-related RM deficit. In Experiment 2, we replicated the results from Experiment 1 using different materials of stimuli and found that the effect of relational attention on RM is material-general. The results of Experiment 2 also showed that reducing attentional resources for relational processing in young adults strikingly equated their RM performance to that of older adults. Thus, the current study documents the first evidence that reduced attentional resources for relational processing are a critical factor for the relational memory impairment observed in aging.
PMCID: PMC3193860  PMID: 21707178
Aging; Episodic memory; Attention; Association
3.  Hepatic angiomyolipoma with minimal fat, mimicking hepatocellular carcinoma 
Clinical and molecular hepatology  2012;18(3):330-335.
PMCID: PMC3467439  PMID: 23091816
Hepatic angiomylolipoma; Hepatocellular carcinoma
4.  Sonography of hepatic hemangioma accompanied by arterioportal shunt 
PMCID: PMC3992336  PMID: 24757664
Hepatic hemangioma; Arterioportal shunt; Doppler
5.  Effect of Dexmedetomidine on the Corrected QT and Tp-e Intervals during Spinal Anesthesia 
Yonsei Medical Journal  2014;55(2):517-522.
The aim of this study is to evaluate the effect of dexmedetomidine on corrected QT (QTc) and Tp-e intervals in patients undergoing spinal anesthesia.
Materials and Methods
We studied 50 patients who were scheduled to undergo spinal anesthesia before orthopedic surgeries. Patients were allocated to receive either an infusion of dexmedetomidine or normal saline after spinal anesthesia.
QTc intervals were significantly prolonged after spinal anesthesia, and the prolonged QTc interval returned to baseline values 10 minutes after either normal saline or dexmedetomidine administration in both groups. The QTc interval values after dexmedetomidine administration were significantly shorter compared to the QTc interval values just before dexmedetomidine administration.
Dexmedetomidine could promote the return of a prolonged QTc interval induced by spinal anesthesia and might be helpful in patients who have a prolonged QTc interval.
PMCID: PMC3936610  PMID: 24532526
Dexmedetomidine; electrocardiogram; spinal anesthesia
6.  Low-Dose Dexmedetomidine Reduces Emergence Agitation after Desflurane Anaesthesia in Children Undergoing Strabismus Surgery 
Yonsei Medical Journal  2014;55(2):508-516.
Emergence agitation (EA) is frequently observed in children undergoing general anaesthesia. This study tested whether the addition of an intra-operative low-dose infusion of dexmedetomidine to fentanyl treatment reduced the incidence of emergence delirium following desflurane anesthesia in children undergoing strabismus surgery.
Materials and Methods
A total of 96 children (1-5 years old) undergoing strabismus surgery were enrolled. Anaesthesia was induced with propofol and maintained with desflurane. After induction, fentanyl (1 µg/kg) was administered to all children. During surgery, patients were infused with 0.2 µg/(kg·h)-1 dexmedetomidine (Group FD, n=47) or normal saline (Group F, n=47). Postoperative objective pain score (OPS), Paediatric Agitation and Emergence Delirium (PAED) score, and EA score were documented every 10 minutes in the post-anaesthesia care unit.
There were no significant differences between the two groups in demographic characteristics and haemodynamic changes. The mean values of maximum EA, maximum PAED, and maximum OPS score were significantly lower in Group FD than in Group F at 0, 10, and 20 minutes after arrival at the post-anaesthesia care unit (p<0.001). The frequency of fentanyl rescue was lower in Group FD than in Group F (p<0.001). The incidence of severe EA was significantly lower in Group FD than in Group F (12.8% vs. 74.5%, p<0.001).
Intra-operative low-dose infusion of dexmedetomidine in addition to fentanyl reduces EA following desflurane anaesthesia in children undergoing strabismus surgeries.
PMCID: PMC3936635  PMID: 24532525
Dexmedetomidine; emergence agitation; objective pain score; pediatrics
7.  Stereotactic Body Radiotherapy-Induced Arterial Hypervascularity of Non-Tumorous Hepatic Parenchyma in Patients with Hepatocellular Carcinoma: Potential Pitfalls in Tumor Response Evaluation on Multiphase Computed Tomography 
PLoS ONE  2014;9(2):e90327.
To evaluate temporal changes in contrast enhancement patterns of non-tumorous hepatic parenchyma with a focus on arterial hypervascularity on multiphase computed tomography (CT) in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).
We retrospectively identified 61 patients who had undergone multiphase contrast-enhanced CT at one, three, and six months after SBRT. Irradiated versus non-irradiated liver parenchyma was delineated by cross-correlation with the dose-volume histogram of SBRT plan. Serial changes in the contrast enhancement patterns of the irradiated versus non-irradiated liver parenchyma were evaluated by two abdominal radiologists in consensus. We compared the frequency of the contrast enhancement patterns according to the follow-up period using the Fisher-Freeman-Halton exact test.
The irradiated non-tumorous hepatic parenchyma showed that the prevalence of arterial hypervascularity increased during the follow-up period (P<.01): 11.5% (7/61) in one, 45.9% (28/61) in three, and 54.1% (33/61) in six months. Contrast wash-out on the delayed phase was uncommon: 1.6% (1/61) in one, 3.3% (2/61) in three, and 0% in six months.
The incidence of arterial hypervascularity of the irradiated hepatic parenchyma gradually increased until six months after SBRT, which could interfere with the accurate evaluation of treatment response. The lack of wash-out on the delayed phase in the hypervascular area would distinguish SBRT-related change from residual/recurred HCC.
PMCID: PMC3938667  PMID: 24587326
8.  Probing enzymatic activity inside living cells using a nanowire-cell “sandwich”assay 
Nano letters  2012;13(1):153-158.
Developing a detailed understanding of enzyme function in the context of an intracellular signal transduction pathway requires minimally invasive methods for probing enzyme activity in situ. Here, we describe a new method for monitoring enzyme activity in living cells by sandwiching live cells between two vertical silicon nanowire (NW) arrays. Specifically, we use the first NW array to immobilize the cells, and then present enzymatic substrates intracellularly via the second NW array by utilizing the NWs’ ability to penetrate cellular membranes without affecting cells’ viability or function. This strategy, when coupled with fluorescence microscopy and mass spectrometry, enables intracellular examination of protease, phosphatase and protein kinase activities, demonstrating the assay’s potential in uncovering the physiological roles of various enzymes.
PMCID: PMC3541459  PMID: 23244056
Silicon nanowire; sandwich assembly; live cell assay; enzyme activity
9.  Effect of Dexmedetomidine on Sevoflurane Requirements and Emergence Agitation in Children Undergoing Ambulatory Surgery 
Yonsei Medical Journal  2013;55(1):209-215.
Dexmedetomidine, a potent selective α2-adrenergic agonist, produces sedation and analgesia. This study was conducted to assess the effect of dexmedetomidine infusion on sevoflurane requirements, recovery profiles, and emergence agitation in children undergoing ambulatory surgery.
Materials and Methods
Forty children undergoing ambulatory hernioplasty or orchiopexy were randomized into two groups. The dexmedetomidine group (Group D, n=20) received dexmedetomidine 1 µg/kg, followed by 0.1 µg/kg/h until the end of surgery, whereas the saline group (Group S, n=20) received volume-matched normal saline. Sevoflurane was used for induction and maintenance of anesthesia and caudal block was performed in all children. End-tidal sevoflurane concentration (ET-sevo), the incidence of emergence agitation, pain scores, and sedation scores were recorded. Hemodynamic changes and other adverse effects were assessed in the perioperative period.
ET-sevo of Group D was significantly reduced in 23.8-67% compared to Group S during surgery. The incidence of emergence agitation was lower in Group D than in Group S (5% vs. 55%, p=0.001). Postoperative pain was comparable, and discharge time was not different between the groups. Mean arterial pressure and heart rate were significantly lower in Group D during surgery.
Intraoperative infusion of dexmedetomidine reduced sevoflurane requirements and decreased emergence agitation without delaying discharge in children undergoing ambulatory surgery. However, caution should be taken in regard to bradycardia and hypotension.
PMCID: PMC3874907  PMID: 24339309
Agitation; ambulatory surgery; dexmedetomidine; emergence; sevoflurane
10.  Overview of the Development of the Korean Exposure Factors Handbook 
A set of exposure factors that reflects the characteristics of individual behavior capable of influencing exposure is essential for risk and exposure assessment. In 2007, the Korean Exposure Factors Handbook was, therefore, issued, driven by the need to develop reliable exposure factors representing the Korean population. The purpose of this study was to overview the development process of the Korean Exposure Factors Handbook and major recommended exposure values for the Korean population to allow information exchanges and comparison of recommended values among nations. The researchers reviewed the domestic data that could be used in the development of exposure factors, confirmed a knowledge gap, and set a priority of development by phases. A methodology to measure exposure factors was established to develop measuring techniques and test their validity. Data were processed or a survey was conducted according to the availability of data. The study thus produced recommended values for 24 exposure factors grouped by general exposure factors, food ingestion factors, and activity factors by setting up a database of exposure factors and carrying out statistical analysis. The study has significantly contributed to reducing the potential uncertainty of the risk and exposure assessment derived by the application of foreign data or research findings lacking representativeness or grounds by developing a set of exposure factors reflecting the characteristics of the Korean people. It will be necessary to conduct revisions in light of the changing statistical values of national data and the exposure factors based on Korean characteristics.
PMCID: PMC3930803  PMID: 24570801
Risk assessment; Environmental exposure; Handbooks
11.  Activity Factors of the Korean Exposure Factors Handbook 
Exposure factors based on the Korean population are required for making appropriate risk assessment. It is expected that handbooks for exposure factors will be applied in many fields, as well as by health department risk assessors. The present article describes the development of an exposure factors handbook that specifically focuses on human activities in situations involving the possible risk of exposure to environmental contaminants. We define majour exposure factors that represent behavioral patterns for risk assessment, including time spent on routine activities, in different places, on using transportation, and engaged in activities related to water contact including swimming, bathing and washing. Duration of residence and employment are also defined. National survey data were used to identify recommended levels of exposure factors in terms of time spent on routine activities and period of residence and employment. An online survey was conducted with 2073 subjects who were selected using a stratified random sampling method in order to develop a list of exposure factors for the time spent in different places and in performing water-related activities. We provide the statistical distribution of the variables, and report reference levels of average exposure based on the reliable data in our exposure factors handbook.
PMCID: PMC3930805  PMID: 24570804
Risk assessment; Handbooks; Environmental exposure
12.  General Factors of the Korean Exposure Factors Handbook 
Risk assessment considers the situations and characteristics of the exposure environment and host. Various physiological variables of the human body reflects the characteristics of the population that can directly influence risk exposure. Therefore, identification of exposure factors based on the Korean population is required for appropriate risk assessment. It is expected that a handbook about general exposure factors will be used by professionals in many fields as well as the risk assessors of the health department. The process of developing the exposure factors handbook for the Korean population will be introduced in this article, with a specific focus on the general exposure factors including life expectancy, body weight, surface area, inhalation rates, amount of water intake, and soil ingestion targeting the Korean population. The researchers used national databases including the Life Table and the 2005 Time Use Survey from the National Statistical Office. The anthropometric study of size in Korea used the resources provided by the Korean Agency for Technology and Standards. In addition, direct measurement and questionnaire surveys of representative samples were performed to calculate the inhalation rate, drinking water intake, and soil ingestion.
PMCID: PMC3930810  PMID: 24570802
Risk assessment; Environmental exposure; Environmental health
13.  Pre-operative factors that can predict neoplastic polypoid lesions of the gallbladder 
AIM: To investigate the preoperative factors that can predict neoplastic polypoid lesions of the gallbladder (PLGs) as well as malignant PLGs.
METHODS: A retrospective analysis was conducted on the 210 consecutively enrolled patients who underwent cholecystectomy due to a PLG larger than 10 mm, as was determined by preoperative trans-abdominal ultrasonography or endoscopic ultrasonography. We analyzed the medical, laboratory, radiologic data and the pathologic results.
RESULTS: In 210 cases, 146 had non-neoplastic polyps (69.5%) and 64 cases were neoplastic polyps (30.5%). An older age (≥ 65 years), the presence of diabetes mellitus (DM) and the size of polyp (≥ 15 mm) were revealed to be independent predictive variables for neoplastic polyps with odd ratios (OR) of 2.27 (P = 0.044), 2.64 (P = 0.021) and 4.94 (P < 0.01), respectively. Among the neoplastic PLGs, an older age (≥ 65 years), the presence of DM and polyp size (≥ 15 mm) were associated with malignancy with ORs of 4.97 (P = 0.005), 6.13 (P = 0.001) and 20.55 (P < 0.001), respectively.
CONCLUSION: Among patients with PLGs larger than 10 mm in size, higher risk groups such as elderly patients more than 65 years old, those with DM or a large polyp size (≥ 15 mm) should be managed by cholecystectomy.
PMCID: PMC3092874  PMID: 21633532
Gallbladder; Polyp; Neoplastic; Cholecystectomy; Diabetes; Pre-operative factors
14.  Stereotactic Body Radiation Therapy as an Alternative Treatment for Small Hepatocellular Carcinoma 
PLoS ONE  2013;8(11):e79854.
Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment.
Materials and Methods
A registry database of 93 patients who were treated with SBRT for HCC between 2007 and 2009 was analyzed. A dose of 10-20 Gy per fraction was given over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. The tumor response was determined using dynamic computed tomography or magnetic resonance imaging, which was performed 3 months after completion of SBRT.
The median follow-up period was 25.6 months. Median size of tumors was 2 cm (range: 1-6 cm). Overall patients’ survival rates at 1 and 3 years were 86.0% and 53.8%, respectively. Complete and partial tumor response were achieved in 15.5% and 45.7% of patients, respectively. Local recurrence-free survival rate was 92.1% at 3 years. Most local failures were found in patients with HCCs > 3 cm, and local control rate at 3 years was 76.3% in patients with HCC > 3 cm, 93.3% in patients with tumors between 2.1-3 cm, and 100% in patients with tumors ≤ 2 cm, respectively. Out-of-field intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively. Grade ≥ 3 hepatic toxicity was observed in 6 (6.5%).
SBRT was effective in local control of small HCC. SBRT may be a promising alternative treatment for patients with small HCC which is unsuitable for other curative therapy.
PMCID: PMC3821847  PMID: 24255719
15.  CD11b+ Gr1+ Bone Marrow Cells Ameliorate Liver Fibrosis by Producing Interleukin-10 in Mice 
Hepatology (Baltimore, Md.)  2012;56(5):1902-1912.
Clinical trials and animal models suggest that infusion of bone marrow cells (BMC) is effective therapy for liver fibrosis, but the underlying mechanisms are obscure, especially those associated with early effects of BMC. Here, we analyzed the early impact of BMC infusion and identified the subsets of BMC showing antifibrotic effects in mice with carbon tetrachloride-induced liver fibrosis. An interaction between BMC and activated hepatic stellate cells (HSCs) was investigated using in vitro co-culturing system. Within 24 hours, infused BMC were in close contact with activated HSCs, which was associated with reduced liver fibrosis, enhanced hepatic expression of interleukin (IL)-10, expanded regulatory T cells but decreased macrophage infiltration in the liver at 24 hours after BMC infusion. In contrast, IL-10-deficient (IL-10−/−) BMC failed to reproduce these effects in the fibrotic livers. Intriguingly, in isolated cells, CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ BMC expressed more IL-10 after co-culturing with activated HSCs, leading to suppressed expression of collagen and α-smooth muscle actin in HSCs. Moreover, these effects were either enhanced or abrogated, respectively, when BMC were co-cultured with IL-6−/− and retinaldehyde dehydrogenase 1−/− HSCs. Similar to murine data, human BMC expressed more IL-10 after co-culturing with human HSC lines (LX-2 or hTERT), and serum IL-10 levels were significantly elevated in patients with liver cirrhosis after autologous BMC infusion.
Activated HSCs increase IL-10 expression in BMC (CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ cells), which in turn ameliorates liver fibrosis. Our findings could enhance the design of BMC therapy for liver fibrosis.
PMCID: PMC3427419  PMID: 22544759
hepatic stellate cell; interleukin-6; regulatory T cell; retinoic acid
16.  Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters 
To investigate the clinical and dose–volumetric parameters that predict the risk of radiation-induced liver disease (RILD) for patients with small, unresectable hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).
Between March 2007 and December 2009, 92 patients with HCC treated with SBRT were reviewed for RILD within 3 months of completing treatment. RILD was evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. A dose of 10–20 Gy (median, 15 Gy) per fraction was given over 3–4 consecutive days for a total dose of 30–60 Gy (median, 45 Gy). The following clinical and dose–volumetric parameters were examined: age, gender, Child-Pugh class, presence of hepatitis B virus, gross tumor volume, normal liver volume, radiation dose, fraction size, mean dose to the normal liver, and normal liver volumes receiving from < 5 Gy to < 60 Gy (in increments of 5 Gy).
Seventeen (18.5%) of the 92 patients developed grade 2 or worse RILD after SBRT (49 patients in grade 1, 11 in grade 2, and 6 in ≥ grade 3). On univariate analysis, Child-Pugh class was identified as a significant clinical parameter, while normal liver volume and normal liver volumes receiving from < 15 Gy to < 60 Gy were the significant dose–volumetric parameters. Upon multivariate analysis, only Child-Pugh class was a significant parameter for predicting grade 2 or worse RILD.
The Child-Pugh B cirrhosis was found to have a significantly greater susceptibility to the development of grade 2 or worse RILD after SBRT in patients with small, unresectable HCC. Additional efforts aimed at testing other models to predict the risk of RILD in a large series of HCC patients treated with SBRT are needed.
PMCID: PMC3816573  PMID: 24160910
Hepatocellular carcinoma; Stereotactic body radiotherapy; Radiation-induced liver disease
17.  Heart rate variability as a predictor of hypotension after spinal anesthesia in hypertensive patients 
Korean Journal of Anesthesiology  2013;65(4):317-321.
Hypotension is a common phenomenon after spinal anesthesia in hypertensive patients. We investigated whether heart rate variability could predict the occurrence of hypotension after spinal anesthesia in hypertensive patients.
Forty-one patients undergoing spinal anesthesia were included. Heart rate variability was measured at five different time points such as before fluid loading (baseline), after fluid loading as well as 5 min, 15 min and 30 min after spinal anesthesia. Fluid loading was performed using 5 ml/kg of a crystalloid solution. Baseline total power and low to high frequency ratio (LF/HF) in predicting hypotension after spinal anesthesia were analyzed by calculating the area under the receiver operating characteristic curves (AUC).
Moderate hypotension, defined as a decrease of mean arterial pressure to below 20-30% of the baseline, occurred in 13 patients and severe hypotension, defined as a decrease of mean arterial pressure greater than 30% below the baseline, occurred in 7 patients. LF/HF ratiosand total powers did not significantly change after spinal anesthesia. AUCs of LF/HF ratio for predicting moderate hypotension was 0.685 (P = 0.074), severe hypotension was 0.579 (P = 0.560) and moderate or severe hypotension was 0.652 (P = 0.101), respectively. AUCs of total power for predicting moderate hypotension was 0.571 (P = 0.490), severe hypotension was 0.672 (P = 0.351) and moderate or severe hypotension was 0.509 (P = 0.924), respectively.
Heart rate variability is not a reliable predictor of hypotension after spinal block in hypertensive patients whose sympathetic activity is already depressed.
PMCID: PMC3822023  PMID: 24228144
Hypertension; Hypotension; Parasympathetic nervous system; Spinal anesthesia; Sympathetic nervous system
18.  Perioperative respiratory adverse events in children with active upper respiratory tract infection who received general anesthesia through an orotracheal tube and inhalation agents 
Korean Journal of Anesthesiology  2013;65(2):136-141.
Active upper respiratory tract infection (URI), orotracheal intubation and use of inhalation anesthetics are known risk factors for perioperative respiratory adverse events (RAE). This study investigated the risk factors of perioperative RAE in children with these risk factors.
The records of 159 children who underwent general anesthesia with an orotracheal tube and inhalation were reviewed. These patients also had at least one of the following URI symptoms on the day of surgery: clear or green nasal secretion, dry or moist cough, nasal congestion, or fever. RAE such as laryngospasm, bronchospasm, oxygen desaturation and sustained cough were collected before induction, during intubation, during extubation, after extubation and in the postanesthesia care unit.
Forty-five patients had RAE. The patients with RAE were younger than those without RAE. There were more passive smokers and a greater number of intubation attempts in patients with RAE than in those without RAE. The type of surgery and type of inhalation agents were not different between patients with and without RAE. Passive smoking was the only independent risk factor for RAE.
In children with an active URI using orotracheal tube and inhalation anesthetics, passive smoking is an important risk factor for RAE.
PMCID: PMC3766779  PMID: 24023996
Child; Perioperative period; Respiratory system; Upper respiratory tract infection
19.  Type-Specific Diagnosis and Evaluation of Longitudinal Tumor Extent of Borrmann Type IV Gastric Cancer: CT versus Gastroscopy 
Korean Journal of Radiology  2013;14(4):597-606.
To compare the accuracy of computed tomography (CT) with that of gastroscopy for the extent of evaluation of longitudinal tumor and type-specific diagnosis of Borrmann type IV gastric cancer.
Materials and Methods
Fifty-nine patients (35 men with mean age of 60 years and 24 women with mean age of 55 years) who underwent surgical resection of Borrmann type IV gastric cancer were included in this study. Histopathological analysis data was used as a reference standard to confirm the clinical interpretations of gastroscopy and CT for the diagnosis of Borrmann type IV and evaluation of longitudinal tumor extent. For the evaluation of longitudinal extent, gastroscopic and CT results were classified as underestimated, accurate, or overestimated. The McNemar test was used to identify statistically significant differences in the accuracy between gastroscopy and CT.
For the diagnosis of Borrmann type IV gastric cancer, the accuracy of CT was significantly higher than that of gastroscopy (74.6% [44/59] vs. 44.1% [26/59], p < 0.001). CT was significantly more accurate in assessing the overall tumor extent than gastroscopy (61.4% [35/57] vs. 28.1% [16/57], p < 0.001). The proximal (75.4% [43/57] vs. 50.9% [29/57], p = 0.003) and distal tumor extent (71.9% [41/57] vs. 43.9% [25/57], p < 0.05) were more accurately predicted by CT compared with gastroscopy. The underestimation of tumor extent was a major source of error in both examinations.
CT was found to be more predictive than gastroscopy in type-specific diagnosis and the evaluation of longitudinal tumor extent in patients with Borrmann type IV gastric cancer.
PMCID: PMC3725354  PMID: 23901317
Stomach; Cancer; CT; Gastroscopy; Borrmann type IV; Linitis plastica
20.  Hesperetin Alleviates the Inhibitory Effects of High Glucose on the Osteoblastic Differentiation of Periodontal Ligament Stem Cells 
PLoS ONE  2013;8(6):e67504.
Hesperetin (3′,5,7-trihydroxy-4-methoxyflavanone) is a metabolite of hesperidin (hesperetin-7-O-rutinoside), which belongs to the flavanone subgroup and is found mainly in citrus fruits. Hesperetin has been reported to be an effective osteoinductive compound in various in vivo and in vitro models. However, how hesperetin effects osteogenic differentiation is not fully understood. In this study, we investigated the capacity of hesperetin to stimulate the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and to relieve the anti-osteogenic effect of high glucose. Osteogenesis of PDLSCs was assessed by measurement of alkaline phosphatase (ALP) activity, and evaluation of the mRNA expression of ALP, runt-related gene 2 (Runx2), osterix (OSX), and FRA1 as osteogenic transcription factors, as well as assessment of protein expression of osteopontin (OPN) and collagen type IA (COLIA). When PDLSCs were exposed to a high concentration (30 mM) of glucose, osteogenic activity decreased compared to control cells. Hesperetin significantly increased ALP activity at doses of 1, 10, and 100 µM. Pretreatment of cells with hesperetin alleviated the high-glucose-induced suppression of the osteogenic activity of PDLSCs. Hesperetin scavenged intracellular reactive oxygen species (ROS) produced under high glucose condition. Furthermore, hesperetin increased the activity of the PI3K/Akt and β-catenin pathways. Consistent with this, blockage of Akt or β-catenin diminished the protective effect of hesperetin against high glucose-inhibited osteogenic differentiation. Collectively, our results suggest that hesperetin alleviates the high glucose-mediated suppression of osteogenic differentiation in PDLSCs by regulating ROS levels and the PI3K/Akt and β-catenin signaling pathways.
PMCID: PMC3696082  PMID: 23840726
21.  Human bone marrow-derived mesenchymal stem cell gene expression patterns vary with culture conditions 
Blood research  2013;48(2):107-114.
Because of the heterogeneity of human mesenchymal stem cells (MSCs), methods for cell expansion in culture and the effects on gene expression are critical factors that need to be standardized for preparing MSCs. We investigated gene expression patterns of MSCs with different seeding densities and culture times.
Bone marrow-derived MSCs were plated at densities from 200 cells/cm2 to 5,000 cells/cm2, and the gene expression patterns were evaluated over time using a reverse-transcription polymerase chain reaction assay.
The mRNA levels of factors that play a critical role in cell migration and tissue regeneration, such as podocalyxin-like protein (PODXL), α4-integrin, α6-integrin, and leukemia inhibitory factor (LIF), were higher in MSCs plated at 200 cells/cm2 than in MSCs plated at 5,000 cells/cm2. The mRNA levels of these factors gradually increased for 10 days and then decreased by day 15 in culture. MSCs seeded at 200 cells/cm2 that were cultured for 10 days expressed high levels of Oct-4 and Nanog. Indoleamine 2,3-dioxygenase, cyclooxygenase-1, and hepatocyte growth factor expression were upregulated in the presence of the proinflammatory cytokine interferon-γ in these cells.
We found differences in the gene expression patterns of MSCs under different culture conditions. MSCs from 10-day cultures seeded at a low density were efficiently expanded, expressed PODXL, α6-integrin, α4-integrin, and LIF, and maintained properties like stemness and immunomodulation. Therefore, ex vivo expansion of MSCs maintained for an adequate culture time after plating at low cell density can provide an effective regenerative medicinal strategy for cell therapies using MSCs.
PMCID: PMC3698395  PMID: 23826579
Mesenchymal stem cell; Gene expression pattern; Seeding density; Culture time; Cell therapy
22.  Nicotinic Acetylcholine Receptor α7 and β4 Subunits Contribute to Nicotine-Induced Apoptosis in Periodontal Ligament Stem Cells 
Molecules and Cells  2012;33(4):343-350.
Nicotine, a major component of cigarette smoking, is the important risk factor for the development of periodontal disease. However, the mechanisms that underlie the cytotoxicity of nicotine in human periodontal ligament stem cells (PDLSCs) are largely unknown. Thus, the purpose of this study was to determine the cytotoxic effect of nicotine by means of nicotinic acetylcholine receptor (nAChR) activation in PDLSCs. We first detected α7 and β4 nAChRs in PDLSCs. The gene expressions of α7 and β4 nAChR were increased by nicotine administration. Nicotine significantly decreased cell viability at a concentration higher than 10−5 M. DNA fragmentation was also detected at high doses of nicotine treatment. Moreover, the detection of sub G1 phase and TUNEL assay demonstrated that nicotine significantly induced apoptotic cell death at 10−2 M concentration. Western blot analysis confirmed that p53 proteins were phosphorylated by nicotine. Under various doses of nicotine, a decrease in the anti-apoptotic protein Bcl-2, but an increase in p53 and cleaved caspase-3 protein levels, was detected in a dose-dependent manner. However, the apoptotic effect of nicotine was inhibited by the pretreatment of α-bungarotoxin, a selective α7 nAChR antagonist or mecamylamine, a non-selective nAChR antagonist. Finally, increases in the subG1 phase and DNA fragmentation by nicotine was attenuated by each nAChR antagonist. Collectively, the presence of α7 and β4 nAChRs in PDLSCs supports a key role of nAChRs in the modulation of nicotine-induced apoptosis.
PMCID: PMC3887805  PMID: 22382680
apoptosis; nAChRs; nicotine; periodontal disease; periodontal ligament stem cells
23.  Monitoring Therapeutic Response in a Case of Extrapulmonary Tuberculosis by Serial F-18 FDG PET/CT 
Due to the low yield of AFB smear and culture in extrapulmonary tuberculosis, therapeutic responses of patients with extrapulmonary tuberculosis are usually monitored clinically and/or radiographically. Such monitoring techniques, however, are not enough to provide effective diagnosis if a remnant lesion exists after treatment. Tuberculosis presents hypermetabolic activity on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) scanning. Reported herein is a case of extrapulmonary tuberculosis where the therapeutic response was assessed via serial F-18 FDG PET/CT scanning, which was useful for detecting the extent of extrapulmonary tuberculosis and for estimating the patient’s therapeutic response.
PMCID: PMC4042972  PMID: 24900035
Extrapulmonary tuberculosis; F-18 FDG PET/CT; Tuberculosis
24.  Successful birth with preimplantation genetic diagnosis using single-cell allele-specific PCR and sequencing in a woman with hypochondroplasia due to FGFR3 mutation (c.1620C>A, p.N540K) 
Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient.
PMCID: PMC3630293  PMID: 23614116
Hypochondroplasia; Preimplantation genetic diagnosis; Receptor, fibroblast growth factor, type 3
25.  Endobronchial Mycobacterium avium Infection in an Immunocompetent Patient 
Infection & Chemotherapy  2013;45(1):99-104.
Although Mycobacterium avium complex (MAC) is the most common pathogen in nontuberculous mycobacterial (NTM) pulmonary diseases, endobronchial lesions caused by MAC infections are very rare even in an immunocompromised host. Herein, we describe the case of a 59-year-old, HIV-negative and non-immunocompromised woman who developed multifocal pulmonary infiltrations with endobronchial lesion caused by M. avium. Bronchoscopic examination revealed white- and yellow-colored irregular mucosal lesions in the bronchus of the left lingular division. M. avium was identified using sputum culture and bronchial washing fluid culture. Following the recommendations of the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA), the patient was begun on treatment with antimycobacterial drugs. After treatment, pneumonic infiltration decreased.
PMCID: PMC3780944  PMID: 24265956
Mycobacterium avium; Immunocompetent host; Nontuberculosis mycobacteria

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