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1.  The Prevalence and Therapeutic Effect of Constipation in Pediatric Overactive Bladder 
Overactive bladder (OAB) is a manifestation of urgency, regardless of urge incontinence, due to involuntary bladder contraction during the storage period. There is a close association between constipation and OAB, but constipation cannot be readily diagnosed. The aims of this study were to evaluate the prevalence of constipation in OAB and the consequent therapeutic effects according to the diagnostic criteria for constipation.
We collected clinical data from 40 children (mean age, 71±22 months) with chief complaints of urgency, frequency, and incontinence. A voiding questionnaire and a 2-day voiding diary were collected, and urinalysis, the Bristol stool scale, and plain abdominal radiography were performed. Constipation was defined as conditions satisfying at least one of the following criteria: Rome III diagnostic criteria, Bristol stool scale types I/II, or a Leech score higher than 8 points as determined by plain radiography. Lower urinary tract symptoms, defecation symptoms, and the bladder volume of patients were examined, and the therapeutic outcomes by constipation diagnostic criteria were evaluated.
Of the 40 OAB patients, 25 had constipation. Among them, 6 had reduced functional bladder capacity (24%; P>0.05). Regarding treatment, in patients who satisfied only one diagnostic criterion, the symptoms improved in 76.9%, 76.9%, and 69.6% of patients meeting the Rome III criteria, Bristol stool scale, and Leech score, respectively (P<0.05). Among the 8 patients satisfying all three criteria, 75% responded to treatment (P<0.05).
The prevalence of constipation in OAB is high. Constipated patients recruited by use of the Rome III criteria, Bristol scale, and Leech score alone and together showed similar outcomes on OAB improvement after the treatment of constipation, which implies that each criterion has the same strength and can be applied comprehensively and generally.
PMCID: PMC3256305  PMID: 22259734
Overactive urinary bladder; Pediatrics; Constipation
2.  Reproducibility of Peripapillary Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography in Pseudophakic Eyes 
To assess the reproducibility of circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurement (measurement agreement) and its color-coded classification (classification agreement) by Cirrus spectral domain optical coherence tomography (OCT) in pseudophakic eyes.
Two-hundred five participants having glaucoma or glaucoma suspected eyes underwent two repeated Cirrus OCT scans to measure cpRNFL thickness (optic disc cube 200 × 200). After classifying participants into three different groups according to their lens status (clear media, cataract, and pseudophakic), values of intra-class coefficient (ICC), coefficient of variance, and test-retest variability were compared between groups for average retinal nerve fiber layer (RNFL) thicknesses and that corresponding to four quadrant maps. Linear weighted kappa coefficients were calculated as indicators of agreement of color code classification in each group.
ICC values were all excellent (generally defined as 0.75 to 1.00) for the average and quadrant RNFL thicknesses in all three groups. ICC values of the clear media group tended to be higher than those in the cataract and pseudophakic groups for all quadrants and average thickness. Especially in the superior and nasal quadrants, the ICC value of the cataract group was significantly lower than that of the clear media and pseudophakic groups. For average RNFL thickness, classification agreement (kappa) in three groups did not show a statistically significant difference. For quadrant maps, classification agreement (kappa) in the clear media group was higher than those in the other two groups.
Agreement of cpRNFL measurement and its color code classification between two repeated Cirrus OCT scans in pseudophakic eyes was as good as that in eyes with clear crystalline lens. More studies are required to ascertain the effect of lens status on the reproducibility of Cirrus OCT according to different stages of glaucoma patients.
PMCID: PMC3958629  PMID: 24688256
Optical coherence tomography; Pseudophakia; Reproducibility of results
3.  Prospects for nucleic acid-based therapeutics against hepatitis C virus 
In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.
PMCID: PMC3870548  PMID: 24379620
Hepatitis C virus; Nucleic acid-based therapeutics; Ribozyme; Aptamer; siRNA; Antisense oligonucleotide
4.  Umbilical cord blood mesenchymal stem cells protect amyloid-β42 neurotoxicity via paracrine 
World Journal of Stem Cells  2012;4(11):110-116.
AIM: To understand the neuroprotective mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) against amyloid-β42 (Aβ42) exposed rat primary neurons.
METHODS: To evaluate the neuroprotective effect of hUCB-MSCs, the cells were co-cultured with Aβ42-exposed rat primary neuronal cells in a Transwell apparatus. To assess the involvement of soluble factors released from hUCB-MSCs in neuroprotection, an antibody-based array using co-cultured media was conducted. The neuroprotective roles of the identified hUCB-MSC proteins was assessed by treating recombinant proteins or specific small interfering RNAs (siRNAs) for each candidate protein in a co-culture system.
RESULTS: The hUCB-MSCs secreted elevated levels of decorin and progranulin when co-cultured with rat primary neuronal cells exposed to Aβ42. Treatment with recombinant decorin and progranulin protected from Aβ42-neurotoxicity in vitro. In addition, siRNA-mediated knock-down of decorin and progranulin production in hUCB-MSCs reduced the anti-apoptotic effects of hUCB-MSC in the co-culture system.
CONCLUSION: Decorin and progranulin may be involved in anti-apoptotic activity of hUCB-MSCs exposed to Aβ42.
PMCID: PMC3536832  PMID: 23293711
Human umbilical cord blood-derived mesenchymal stem cells; Decorin; Progranulin; Aβ42; Anti-apoptosis
5.  Current status of endoscopic submucosal dissection for the management of early gastric cancer: A Korean perspective 
The early diagnosis of gastric cancer allows patients and physicians to pursue the option of endoscopic resection, which is significantly less invasive than conventional surgical resection. In Korea, the use of endoscopic submucosal dissection (ESD) has been increasing, and many reports on ESD have been published. In addition, Korean gastroenterologists from several hospitals performing ESD have conducted formal meetings to discuss useful information regarding ESD. Here, we discuss the Korean experience with ESD, including outcomes and prospects of endoscopic treatments.
PMCID: PMC3110919  PMID: 21677825
Early gastric cancer; Endoscopic submucosal dissection; Endoscopic mucosal resection
6.  Estimation of 24-Hour Urinary Sodium Excretion Using Spot Urine Samples 
Nutrients  2014;6(6):2360-2375.
The present study evaluated the reliability of equations using spot urine (SU) samples in the estimation of 24-hour urine sodium excretion (24-HUNa). Equations estimating 24-HUNa from SU samples were derived from first-morning SU of 101 participants (52.4 ± 11.1 years, range 24–70 years). Equations developed by us and other investigators were validated with SU samples from a separate group of participants (n = 224, 51.0 ± 10.9 years, range 24–70 years). Linear, quadratic, and cubic equations were derived from first-morning SU samples because these samples had a sodium/creatinine ratio having the highest correlation coefficient for 24-HUNa/creatinine ratio (r = 0.728, p < 0.001). In the validation group, the estimated 24-HUNa showed significant correlations with measured 24-HUNa values. The estimated 24-HUNa by the linear, quadratic, and cubic equations developed from our study were not significantly different from measured 24-HUNa, while estimated 24-HUNa by previously developed equations were significantly different from measured 24-HUNa values. The limits of agreement between measured and estimated 24-HUNa by six equations exceeded 100 mmol/24-hour in the Bland-Altman analysis. All equations showed a tendency of under- or over-estimation of 24-HUNa, depending on the level of measured 24-HUNa. Estimation of 24-HUNa from single SU by equations as tested in the present study was found to be inadequate for the estimation of an individual’s 24-HUNa.
PMCID: PMC4073156  PMID: 24955740
sodium intake; spot urine; 24-hour collection
7.  Difference of Diagnostic Rates and Analytical Methods in the Test Positions of Vestibular Evoked Myogenic Potentials 
Annals of Rehabilitation Medicine  2014;38(2):226-233.
To compare the differences of diagnostic rates, of the two widely used test positions, in measuring vestibular evoked myogenic potentials (VEMP) and selecting the most appropriate analytical method for diagnostic criteria for the patients with vertigo.
Thirty-two patients with vertigo were tested in two comparative testing positions: turning the head to the opposite side of the evaluating side and bowing while in seated position, and bowing while in supine positions. Abnormalities were determined by prolonged latency of p13 or n23, shortening of the interpeak latency, and absence of VEMP formation.
Using the three criteria above for determining abnormalities, both the seated and supine positions showed no significant differences in diagnostic rates, however, the concordance correlation of the two positions was low. When using only the prolonged latency of p13 or n23 in the two positions, diagnostic rates were not significantly different and their concordance correlation was high. On the other hand, using only the shortened interpeak latency in both positions showed no significant difference of diagnostic rates, and the degree of agreement between two positions was low.
Bowing while in seated position with the head turned in the opposite direction to the area being evaluated is found to be the best VEMP test position due to the consistent level of sternocleidomastoid muscle tension and the high level of compliance. Also, among other diagnostic analysis methods, using prolonged latency of p13 or n23 as the criterion is found to be the most appropriate method of analysis for the VEMP test.
PMCID: PMC4026609  PMID: 24855617
Vestibular evoked myogenic potentials (VEMP); Patient positioning; Data interpretation
8.  Distribution of CD10-positive epithelial and mesenchymal cells in human mid-term fetuses: a comparison with CD34 expression 
Anatomy & Cell Biology  2014;47(1):28-39.
CD10, a marker of immature B lymphocytes, is expressed in the developing epithelium of mammary glands, hair follicles, and renal tubules of human fetuses. To assess mesenchymal and stromal expression of CD10, we performed immunohistochemical assays in whole body sections from eight fetuses of gestational ages 15-20 weeks. In addition to expression in urinary tract and intestinal epithelium, CD10 was strongly expressed at both gestational ages in fibrous tissues surrounding the airways from the larynx to lung alveoli, in the periosteum and ossification center, and in the glans of external genitalia. CD10 was not expressed, however, in other cavernous tissues. These findings suggest that mesenchymal, in addition to epithelial cells at specific sites, are likely to express CD10. The glomeruli, alveoli, and glans are all end products of budding or outgrowth processes in the epithelium or skin. However, in contrast to the CD34 marker of stromal stem cells, CD10 was not expressed in vascular progenitor cells and in differentiated vascular endothelium. The alternating pattern of CD10 and CD34 expression suggests that these factors play different roles in cellular differentiation and proliferation of the kidneys, airway and external genitalia.
PMCID: PMC3968264  PMID: 24693480
CD10; Epithelium; Mesoderm; Human fetus
9.  The Efficacy of Endoscopic Submucosal Dissection of Type I Gastric Carcinoid Tumors Compared with Conventional Endoscopic Mucosal Resection 
Background and Aims. Conventional endoscopic submucosal resection (EMR) of carcinoid tumors often involves the resection margin, which necessitates further intervention. Endoscopic submucosal dissection (ESD) is widely accepted for removing carcinoid tumors. We aimed to evaluate the clinical usefulness of ESD with that of EMR for resection of type I gastric carcinoid tumors. Patients and Methods. The study enrolled 62 patients (37 males, 25 females; median age, 50 years; range, 40–68 years) who were treated with EMR or ESD at three hospitals; the study group had 87 type I gastric carcinoid tumors with an estimated size of ≤10 mm. The complete resection rate and the complications associated with these two procedures were analyzed. Results. The overall ESD complete resection rate was higher than that of the EMR rate (94.9% versus 83.3%, P value = 0.174). A statistically lower vertical margin involvement rate was achieved when ESD was performed compared to when EMR was performed (2.6% versus 16.7%, P value = 0.038). The complication rate was not significantly different between the two groups. Conclusions. ESD showed a higher complete resection rate, particularly for the vertical margin, with a similar complication rate. We mildly recommend ESD rather than EMR for removing type I gastric carcinoid tumors.
PMCID: PMC3947882  PMID: 24693280
10.  High Sodium Intake in Women with Metabolic Syndrome 
Korean Circulation Journal  2014;44(1):30-36.
Background and Objectives
Metabolic syndrome and high sodium intake are associated with frequent cardiovascular events. Few studies have estimated sodium intake in subjects with metabolic syndrome by 24-hour urine sodium excretion. We evaluated sodium intake in individuals with metabolic syndrome.
Subjects and Methods
Participants were recruited by random selection and through advertisement. Twenty four-hour urine collection, ambulatory blood pressure measurements, and blood test were performed. Sodium intake was estimated by 24-hour urine sodium excretion. Participants receiving antihypertensive medications were excluded from analysis.
Among the 463 participants recruited, subjects with metabolic syndrome had higher levels of 24-hour urine sodium excretion than subjects without metabolic syndrome (p=0.0001). There was a significant relationship between the number of metabolic syndrome factors and 24-hour urine sodium excretion (p=0.001). The proportion of subjects with metabolic syndrome was increased across the tertile groups of 24-hour urine sodium excretion (p<0.0001). The association of high sodium intake and metabolic syndrome was significant only among women. Among the factors related to metabolic syndrome, body mass index had an independent association with 24-hour urine sodium excretion (p<0.0001).
Women with metabolic syndrome exhibited significantly higher sodium intake, suggesting that dietary education to reduce sodium consumption should be emphasized for women with metabolic syndrome.
PMCID: PMC3905113  PMID: 24497887
Sodium, dietary; Metabolic syndrome; Hypertension
11.  The effect of bonded resin surface area on the detachment force of lingual bonded fixed retainers: An in vitro study 
Korean Journal of Orthodontics  2014;44(1):20-27.
The aims of this study were to evaluate the relationship between the detachment force and bonding resin surface are and to determine the resin bonding surface area that would provide adequate bonding strength with minimum resin volume.
One hundred and sixty human premolars were randomly divided into 4 groups of 40 teeth each. The diameter of the resin surface area in each group was as follows: group 1, 1.5 mm; group 2, 2.5 mm; group 3, 3.5 mm; and group 4, 4.5 mm. Respond Dead Soft straight (length 0.0175 inch) was used to fabricate the retainers, and Transbond™ XT was used to fix the retainers to the tooth surfaces. A pair of teeth was embedded in acrylic blocks for each specimen. Thus, each group comprised 20 samples. Fixed retainers were bonded to the teeth, and vertical force was applied at the middle of wire. The force was measured using a universal testing machine.
The mean value of detachment force was the highest for group 4 (102.38 ± 2.92 N), followed by group 3 (63.54 ± 2.21 N), group 2 (51.95 ± 1.61 N), and group 1 (24.14 ± 1.38 N).
The detachment force of lingual fixed retainers was significantly affected as the area of the resin bonding surface increased. Considering the minimum bonding strength of brackets, a resin bonding surface area with a diameter of 3.5 mm would provide adequate bonding strength.
PMCID: PMC3915172  PMID: 24511512
Lingual fixed retainer; Surface area; Bonding strength
12.  Effects of ECM Protein Mimetics on Adhesion and Proliferation of Chorion Derived Mesenchymal Stem Cells 
Background: We evaluated the effects of fibronectin, collagen, cadherin, and laminin based extracellular matrix (ECM) protein mimetics coated with mussel derived adhesive protein (MAP) on adhesion and proliferation of chorionic mesenchymal stem cells (cMSCs).
Methods: Human placental chorionic tissues from term third-trimester pregnancies (n=3) were used. The cMSCs were cultured on rationally designed ECM protein mimetics coated with MAP on plastic surfaces with the addition of reduced fetal bovine serum (0.5%, 1% FBS). Adhesion capabilities were monitored by a real time cell analysis system (RTCA) utilizing an impedance method. Proliferation capabilities were monitored by RTCA and MTS assay.
Results: Of the ECM protein mimetics tested, GRGDSP(FN) coated surfaces exhibited the highest adhesion and proliferation capabilities on RTCA at FBS concentration of 0.5% and 1%. When 0.5% FBS was added to ECM protein mimetics during the MTS assay, GRGDSP(FN), REDV(FN), and collagen mimetics, GPKGAAGEPGKP(ColI) showed higher cMSCs proliferation compared with the control. When 1% FBS was added, GRGDSP(FN) and TAIPSCPEGTVPLYS(ColIV) showed significant cMSCs proliferation capacity.
Conclusions: Fibronectin mimetics, GRGDSP(FN) amino acid sequence showed the highest adhesion and proliferation capabilities. In addition, results from RTCA assessment of cell viability correlated well with the tetrazolium-based MTS assay.
PMCID: PMC3917120  PMID: 24516355
chorionic mesenchymal stem cell; extracellular matrix; protein mimetics; real time cell analysis; cell proliferation assay.
13.  Leptomeningeal carcinomatosis from gastric cancer: single institute retrospective analysis of 9 cases 
The aim of this study is to investigate the clinical features and outcomes of 9 consecutive patients who suffered with leptomeningeal carcinomatosis (LMC) originating from gastric cancer.
Between January 1995 and December 2010, we retrospectively reviewed the medical records of 9 patients with gastric LMC who had been treated at St. Vincent's Hospital, The Catholic University of Korea.
With the exception of 1 patient, the primary gastric cancer was Borrmann type III or IV, and 5 cases had poorly differentiated or signet ring cell histology. TNM stage of the primary gastric cancer was III in 6 patients. The median interval from diagnosis of the primary malignancy to the diagnosis of LMC was 9 months. Headache (6 cases), altered mental status (4 cases), and dysarthria (3 cases) were presenting symptoms of LMC. Computed tomography findings were abnormal in 4 of 7 cases, while magnetic resonance imaging revealed abnormality in 4 of 5 cases. Radiation therapy was administered to 5 patients and intrathecal chemotherapy was administered to only 1 patient. Median overall survival duration from the diagnosis of LMC was 3 months.
LMC originating from gastric cancer had a fatal clinical course and treatment strategies remain challenging.
PMCID: PMC3994606  PMID: 24761402
Stomach neoplasms; Neoplasm metastasis; Meningeal carcinomatosis; Prognosis
14.  Site-Specific Distribution of CD68-Positive Microglial Cells in the Brains of Human Midterm Fetuses: A Topographical Relationship with Growing Axons 
BioMed Research International  2013;2013:762303.
Using 5 fetuses of gestational age (GA) of 15-16 weeks and 4 of GA of 22–25 weeks, we examined site- and stage-dependent differences in CD68-positive microglial cell distribution in human fetal brains. CD68 positive cells were evident in the floor of the fourth ventricle and the pons and olive at 15-16 weeks, accumulating in and around the hippocampus at 22–25 weeks. At both stages, the accumulation of these cells was evident around the optic tract and the anterior limb of the internal capsule. When we compared CD68-positive cell distribution with the topographical anatomy of GAP43-positive developing axons, we found that positive axons were usually unaccompanied by CD68-positive cells, except in the transpontine corticofugal tract and the anterior limb of the internal capsule. Likewise, microglial cell distribution did not correspond with habenulointerpeduncular tract. Therefore, the distribution of CD68-positive cells during normal brain development may not reflect a supportive role of these microglia in axonogenesis of midterm human fetuses.
PMCID: PMC3891602  PMID: 24459672
15.  Inhibition of Hepatitis C Virus (HCV) Replication by Specific RNA Aptamers against HCV NS5B RNA Replicase 
Journal of Virology  2013;87(12):7064-7074.
This study identified specific and avid RNA aptamers consisting of 2′-hydroxyl- or 2′-fluoropyrimidines against hepatitis C virus (HCV) NS5B replicase, an enzyme that is essential for HCV replication. These aptamers acted as potent decoys to competitively impede replicase-catalyzed RNA synthesis activity. Cytoplasmic expression of the 2′-hydroxyl aptamer efficiently inhibited HCV replicon replication in human liver cells through specific interaction with, and sequestration of, the target protein without either off-target effects or escape mutant generation. A selected 2′-fluoro aptamer could be truncated to a chemically manufacturable length of 29 nucleotides (nt), with increase in the affinity to HCV NS5B. Noticeably, transfection of the truncated aptamer efficiently suppressed HCV replication in cells without escape mutant appearance. The aptamer was further modified through conjugation of a cholesterol or galactose-polyethylene glycol ligand for in vivo availability and liver-specific delivery. The conjugated aptamer efficiently entered cells and inhibited genotype 1b subgenomic and genotype 2a full-length HCV JFH-1 RNA replication without toxicity and innate immunity induction. Importantly, a therapeutically feasible amount of the conjugated aptamer was delivered in vivo to liver tissue in mice. Therefore, cytoplasmic expression of 2′-hydroxyl aptamer or direct administration of chemically synthesized and ligand-conjugated 2′-fluoro aptamer against HCV NS5B could be a potent anti-HCV approach.
PMCID: PMC3676086  PMID: 23596299
16.  Expression of carbonic anhydrase IX in human fetal joints, ligaments and tendons: a potential marker of mechanical stress in fetal development? 
Anatomy & Cell Biology  2013;46(4):272-284.
Carbonic anhydrase type IX (CA9) is known to express in the fetal joint cartilage to maintain pH against hypoxia. Using paraffin-embedded histology of 10 human fetuses at 10-16 weeks of gestation with an aid of immunohistochemistry of the intermediate filaments, matrix components (collagen types I and II, aggrecan, versican, fibronectin, tenascin, and hyaluronan) and CA9, we observed all joints and most of the entheses in the body. At any stages examined, CA9-poisitive cells were seen in the intervertebral disk and all joint cartilages including those of the facet joint of the vertebral column, but the accumulation area was reduced in the larger specimens. Glial fibrillary acidic protein (GFAP), one of the intermediate filaments, expressed in a part of the CA9-positive cartilages. Developing elastic cartilages were positive both of CA9 and GFAP. Notably, parts of the tendon or ligament facing to the joint, such as the joint surface of the annular ligament of the radius, were also positive for CA9. A distribution of each matrix components examined was not same as CA9. The bone-tendon and bone-ligament interface expressed CA9, but the duration at a site was limited to 3-4 weeks because the positive site was changed between stages. Thus, in the fetal entheses, CA9 expression displayed highly stage-dependent and site-dependent manners. CA9 in the fetal entheses seemed to play an additional role, but it was most likely to be useful as an excellent marker of mechanical stress at the start of enthesis development.
PMCID: PMC3875845  PMID: 24386600
Carbonic anhydrase type IX; Intermediate filaments; Joints; Enthesis; Human fetus
18.  Usefulness of 18F-FDG PET/CT for the Evaluation of Bone Marrow Involvement in Patients with High-Grade Non-Hodgkin’s Lymphoma 
To assess the usefulness of 18F-fluorodeoxyglucose PET/CT in the detection of bone marrow (BM) involvement of high-grade non-Hodgkin’s lymphoma (NHL).
One hundred twenty patients with newly diagnosed diffuse large B-cell lymphoma or peripheral T-cell lymphoma between January 2007 and June 2011, who received BM trephine biopsy and 18F-FDG PET/CT before chemotherapy, were included in this retrospective study. We reviewed their 18F-FDG PET/CT images and bone marrow biopsy (BMB) results. After reviewing the images, we reviewed the medical records and radiological findings of interesting patients.
There were 23 18F-FDG PET/CT scans in which the marrow was considered to be abnormal (either positive or equivocal), and 97 18F-FDG PET/CT scans were regarded as having negative FDG uptake. Of 120 patients, 100 (83.3 %) had a concordant result of BM interpretation between 18F-FDG PET/CT and BMB, and the remaining 20 patients had discordant results. Among 23 patients with either positive or equivocal 18F-FDG PET/CT scans, 1 of 12 patients with ‘positive’ 18F-FDG PET/CT had a lymphomatous involvement on BMB. In contrast, 10 of 11 patients with ‘equivocal’ BM hypermetabolism were reported as having positive involvement by BMB. Patients with abnormal 18F-FDG PET/CT had significantly higher mSUVhighest than those with normal FDG-PET/CT.
18F-FDG PET/CT and BMB are complementary techniques in assessing the presence of BM involvement in patients with high-grade NHL. The increasing availability of 18F-FDG PET/CT will raise the need for additional biopsy for FDG-avid lesions, especially in patients with negative standard BMBs. 18F-FDG PET/CT can be useful as a decision-making tool for determining whether to perform a standard BMB or targeted biopsy to the FDG-avid lesion as an initial staging procedure. A direct bone biopsy for FDGpositive bone lesions should be included in staging guidelines in future. In 18F-FDG PET/CT-negative cases, BMB is still a powerful procedure, but BMB alone is insufficient for full evaluation of BM.
PMCID: PMC4043073  PMID: 24900074
18F-FDG PET/CT; Lymphoma; Bone marrow
19.  Learning Curve of Capsule Endoscopy 
Clinical Endoscopy  2013;46(6):633-636.
Capsule endoscopy (CE) has become an important tool for the diagnosis of small bowel disease. Although CE does not require the skill of endoscope insertion, the images should be interpreted by a person with experience in assessing images of the gastrointestinal mucosa. This investigation aimed to document the number of cases needed by trainees to gain the necessary experience for CE competency.
Fifteen cases were distributed to 12 trainees with no previous experience of CE during their gastroenterology training as clinical fellows. Twelve trainees and an expert were asked to read CE images from one patient each week for 15 weeks. The diagnosis was reported using five categories (no abnormalities detected, small bowel erosion or ulcer, small bowel tumor, Crohn disease, and active small bowel bleeding with no identifiable source). We then examined, using the κ coefficient, how the degree of mean agreements between the trainees and the expert changed as the training progressed each week.
The agreement rate of CE diagnosis increased as the frequencies of interpretation increased. Most of the mean κ coefficients were >0.60 and >0.80 after week 9 and 11, respectively.
Experience with approximately 10 cases of CE is appropriate for trainees to attain CE competency.
PMCID: PMC3856264  PMID: 24340256
Capsule endoscopy; Learning curve
20.  A Pilot Study on the Effect of Functional Electrical Stimulation of Stroke Patients in a Sitting Position on Balance and Activities of Daily Living 
Journal of Physical Therapy Science  2013;25(9):1097-1101.
[Purpose] This study investigated the effect of functional electrical stimulation (FES) of stroke patients in a sitting position on balance and activities of daily living. [Methods] FES was applied to stroke patients (six male, three female) while in a sitting and supine position. FES was applied six times for 30 minutes each for a total of six weeks. [Results] The timed up and go (TUG) values at weeks 2, 4, and 6 after FES treatment in a sitting position were noticeably decreased in a time-dependent manner, compared with controls. In the sitting, the functional reach test (FRT) values were significantly increased in a time-dependent manner. The same values in the supine position weakly showed a similar pattern to those in the sitting position. Furthermore, the functional independent measurement (FIM) values in the sitting position were markedly increased in a time-dependent manner. In the sitting position, the intensity of FES was markedly decreased in a time-dependent manner. The same values in the supine position weakly showed a similar pattern to those in the sitting position. [Conclusion] These results suggest that the conditions of stroke patients in both the sitting and supine positions after FES treatment were improved and that FES had a greater effect in the sitting position.
PMCID: PMC3818750  PMID: 24259923
Functional electrical stimulation; Sitting position; Stroke patients
21.  Impulsive Behavior and Recurrent Major Depression Associated with Dandy-Walker Variant 
Psychiatry Investigation  2013;10(3):303-305.
Reported herein is a case of recurrent major depression with impulse control difficulty in a 33-year-old man with Dandy-Walker variant. He was diagnosed as having major depressive disorder a year before he presented himself to the authors' hospital, and had a history of three-time admission to a psychiatric unit in the previous 12 months. He was readmitted and treated with sodium valporate 1,500 mg/day, mirtazapine 45 mg/day, and quetiapine 800 mg/day during the three months that he was confined in the authors' hospital, and the symptoms were reduced within three months but remained thereafter. This is the only case so far reporting recurrent depression with impulse control difficulty associated with Dandy-Walker variant. This case implies that any cerebellar lesion may cause the appearance of recurrent depression with impulse control difficulty in major depressive disorder.
PMCID: PMC3843025  PMID: 24302956
Dandy-Walker variant; Cerebellum; Depression; Impulse control; Aggression
22.  Instability at Short Tandem Repeats in Lymphoblastoid Cell Lines 
Epstein Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) are a useful biological resource, however, genomic variations can happen during the generation and immortalization processes of LCLs. The purpose of this study was to identify genomic variations in LCL DNA compared with matched blood DNA using short tandem repeats (STRs) analysis.
We analyzed 15 STRs with blood DNA and their matched LCL DNA samples from 6645 unrelated healthy individuals.
Mutations (such as repeat variations and triallelic patterns) of 15 STR loci were detected in 612 LCL DNAs (9.2% of total) without mutations in their matched blood DNA. The repeat variations of 15 STRs were detected in 526 LCL DNAs (mutation rate = 0.0792) and triallelic patterns were identified in 123 (mutation rate = 0.0185). Among 15 STRs, the most common repeat variations (n = 214, mutation rate = 0.0322) and triallelic patterns (n = 17, mutation rate = 0.0026) were found at FGA locus.
Our study shows that mutations in STRs can occur during generation and immortalization of LCLs.
PMCID: PMC3767104  PMID: 24159555
lymphoblastoid cell lines; short tandem repeats
23.  Heterogeneity of glandular cells in the human salivary glands: an immunohistochemical study using elderly adult and fetal specimens 
Anatomy & Cell Biology  2013;46(2):101-112.
Using immunohistochemical staining for alpha-smooth muscle actin (α-SMA), glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14 (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of major and minor salivary glands obtained from 14 donated cadavers (78-92 years old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63 expression was investigated only in the adult specimens. SMA was detected in all adult glands as well as in fetal sublingual and pharyngeal glands. GFAP expression was seen in a limited number of cells in adult glands, but was highly expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were present in adult minor glands as well as in fetal sublingual and pharyngeal glands. Expression of p63 was evident in the ducts of adult glands. CK14 immunoreactivity was observed in a limited number of glandular cells in adults, in contrast to consistent expression of CK19. In both adults and fetuses, a mosaic expression pattern was usually evident for each of the examined proteins. A difference in immunoreactivity for the nerve markers GFAP and S100 was observed between the major and minor glands. Thus, in the present histologic study, we distinguished between the specific gland types on the basis of their immunohistochemical staining. A mosaic expression pattern suggested that the immunoreactivity against nerve protein markers in myoepithelial cells could not be due to the persistence of neural crest remnants or the physiological status of the gland, such as age-related degeneration.
PMCID: PMC3713274  PMID: 23869257
Salivary glands; Myoepithelial cells; Immunohistochemistry; Adult; Fetus
24.  Influence of developing ligaments on the muscles in contact with them: a study of the annular ligament of the radius and the sacrospinous ligament in mid-term human fetuses 
Anatomy & Cell Biology  2013;46(2):149-156.
The supinator muscle originates from the annular ligament of the radius, and the muscle fibers and ligament take a similar winding course. Likewise, the coccygeus muscle and the sacrospinous ligament are attached together, and show a similar fiber orientation. During dissection of adult cadavers for our educational curriculum, we had the impression that these ligaments grow in combination with degeneration of parts of the muscles. In histological sections of 25 human fetuses at 10-32 weeks of gestation, we found that the proximal parts of the supinator muscle were embedded in collagenous tissue when the developing annular ligament of the radius joined the thick intermuscular connecting band extending between the extensor carpi radialis and anconeus muscles at 18-22 weeks of gestation, and the anterior parts of the coccygeus muscle were surrounded by collagenous tissue when the intramuscular tendon became the sacrospinous ligament at 28-32 weeks. Parts of these two muscles each seemed to provide a mold for the ligament, and finally became involved with it. This may be the first report to indicate that a growing ligament has potential to injure parts of the "mother muscle," and that this process may be involved in the initial development of the ligament.
PMCID: PMC3713279  PMID: 23869262
Supinator muscle; Coccygeus muscle; Sacrospinous ligament; Annular ligament of the radius; Human fetus
25.  Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells 
Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.
PMCID: PMC3684033  PMID: 23818927

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