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1.  Outcomes of Transurethral Removal of Intravesical or Intraurethral Mesh Following Midurethral Sling Surgery 
Korean Journal of Urology  2011;52(12):829-834.
To present outcomes of transurethral removal (TUR) of intravesical or intraurethral mesh after midurethral slings.
Materials and Methods
This was a retrospective chart review of 23 consecutive women: 20 with intravesical mesh and 3 with intraurethral mesh.
To remove the mesh, transurethral resection with an electrode loop (TUR-E) was used in 16 women and transurethral resection with a holmium laser (TUR-H) was used in 7. The median follow-up was 2.1 months. Twenty-six percent of the women (6/23) had a mesh remnant: 6.2% (1/16) of the women treated with TUR-E and 71.4% (5/7) of the women treated with TUR-H. Of the 5 women treated with TUR-H, 3 underwent concomitant transvaginal removal. On the follow-up cystoscopic exam, a mesh remnant was observed in 3 women (1 treated with TUR-E and 2 treated with TUR-H). Vesico-vaginal fistulas were found in 2 women during and after TUR-E, respectively. Stress urinary incontinence recurred in 1 woman.
TUR-E has a high success rate but carries a risk of bladder perforation. Complete resection using TUR-H depends on the location of the mesh and the range of motion of the instrument.
PMCID: PMC3246515  PMID: 22216395
Complications; Management; Suburethral slings
2.  Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B 
AIM: To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naïve chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone.
METHODS: Eighty patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus (HBV) DNA at 0, 12 and 48 wk and serum alanine aminotransferase (ALT) levels after 0, 12, 24 and 48 wk of adefovir treatment in each group.
RESULTS: We found serum ALT became normalized in 72 (87.5%) of the 80 patients, and HBV DNA decreased by ≥ 2 log10 copies/mL in 60 (75%) of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups.
CONCLUSION: These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.
PMCID: PMC2695919  PMID: 18350610
Adefovir dipivoxil; Chronic hepatitis B; Hepatitis B virus DNA; Overlap
3.  Risk factors for contralateral patent processus vaginalis determined by transinguinal laparoscopic examination 
Concurrent contralateral inguinal exploration in children with unilateral hernia or hydrocele is a subject of debate. The aim of the present study was to investigate the incidence of contralateral patent processus vaginalis (CPPV) using transinguinal laparoscopy (inguinoscopy). In addition, the risk factors of CPPV were evaluated in order to facilitate the selection of appropriate candidates for contralateral examination. A total of 119 patients who presented with unilateral hydrocele, inguinal hernia or cryptorchidism between 2001 and 2008 underwent inguinoscopy during the ipsilateral surgery. All data were collected prospectively. The incidence of CPPV was investigated and the risk factors affecting the presence of CPPV were analyzed. Among these patients, 29 individuals (24.4%) had CPPV confirmed by inguinoscopy. No surgical complications were observed during the inguinoscopy. Cases with suspicious ultrasound findings were at a higher risk of CPPV than cases with normal findings (odds ratio, 13.800; P=0.004). A history of contralateral disease was also found to be a significant risk factor (odds ratio, 4.008; P=0.019). The present study identified that the significant risk factors for CPPV were suspicious findings on ultrasound examination and a history of contralateral disease. Therefore, it is concluded that performing inguinoscopy in children with these risk factors is beneficial.
PMCID: PMC4280956  PMID: 25574209
hydrocele; inguinal hernia; contralateral; laparoscopy
5.  Treatment Outcomes of Transurethral Macroplastique Injection for Postprostatectomy Incontinence 
Korean Journal of Urology  2014;55(3):182-189.
We investigated the efficacy of transurethral injection of Macroplastique bulking agent (Uroplasty) for male stress urinary incontinence (SUI) after prostate surgery.
Materials and Methods
This retrospective review included men with SUI treated by transurethral injection for symptoms resulting from prostate surgery. Patients were evaluated at 1 month and 6 months after injection by determining the number of pads used per day and changes in incontinence symptoms. Treatment success was defined as use of 1 pad or fewer per day combined with subjective symptom improvement.
The study population comprised 30 men with a mean age of 66.1±5.3 years. Of the 30 patients, 24 (80.0%) underwent prostate cancer surgery and the remaining 6 (20.0%) underwent surgery for benign prostatic hyperplasia. The preinjection pad number was 2.9±1.9 pads per day. After injection treatment, the mean follow-up period was 9.3±12.7 months and the success rate was 43% (13/30) at 1 month and 32% (6/19) at 6 months. Injection was more likely to result in a successful outcome in patients with no preinjection radiation treatment history and higher abdominal leak point pressure (ALPP) than in those with a previous history of radiation treatment and lower ALPP, although this result was not statistically significant. Acute urinary retention occurred in 5 patients (17%).
Transurethral Macroplastique injection treatment is a relatively non-invasive treatment method for male SUI with a success rate of 43% at 1 month and 32% at 6 months. Patients with a higher ALPP and no previous history of radiation therapy may experience better treatment outcomes.
PMCID: PMC3956947  PMID: 24648873
Dimethylpolysiloxanes; Male; Prostate; Urethra; Urinary incontinence
6.  Diagnostic Role of Prostate Resection in the Elderly Patients Who Experience Significant Co-Morbidity with a High Clinical Suspicion of Prostate Cancer 
Journal of Korean Medical Science  2013;28(12):1796-1800.
The necessity of routine prostate biopsy prior to transurethral resection of the prostate (TURP) in elderly comorbid patients with a high prostate specific antigen (PSA) level remains controversial. We assessed the role of TURP in prostate cancer diagnosis in these individuals. A total of 197 patients underwent TURP in conjunction with prostatic needle biopsy. Pathologic reviews of specimens of TUR chips and biopsy cores were analyzed. Overall, prostate cancer (CaP) was detected in 114 patients (57.6%). Ninety-eight cancers (86%) were detected with TURP and biopsy, and seven cancers (6.1%) with only TURP. The Gleason score of a TUR-specimen was identical to that of the biopsy-core in 43.9% of cases. Variables associated with diagnostic accuracy in the TUR-specimens included the prebiopsy PSA level, prostate specific antigen density (PSAD), and the Gleason score in biopsy cores. In patients with a PSA level and a PSAD that was greater than 15.4 ng/mL and 0.69 ng/mL/g, respectively, 100% of the cancers were detected in the TUR-specimens. Our results suggest that a prostatic biopsy might be omitted prior to TURP in elderly patients with significant co-morbidity and levels for PSA of >15.4 ng/mL.
PMCID: PMC3857377  PMID: 24339711
Prostate Neoplasms; Transurethral Prostatic Resection of Prostate; Transrectal Prostate Biopsy; Prostate-Specific Antigen
7.  Ontology-aware classification of tissue and cell-type signals in gene expression profiles across platforms and technologies 
Bioinformatics  2013;29(23):3036-3044.
Motivation: Leveraging gene expression data through large-scale integrative analyses for multicellular organisms is challenging because most samples are not fully annotated to their tissue/cell-type of origin. A computational method to classify samples using their entire gene expression profiles is needed. Such a method must be applicable across thousands of independent studies, hundreds of gene expression technologies and hundreds of diverse human tissues and cell-types.
Results: We present Unveiling RNA Sample Annotation (URSA) that leverages the complex tissue/cell-type relationships and simultaneously estimates the probabilities associated with hundreds of tissues/cell-types for any given gene expression profile. URSA provides accurate and intuitive probability values for expression profiles across independent studies and outperforms other methods, irrespective of data preprocessing techniques. Moreover, without re-training, URSA can be used to classify samples from diverse microarray platforms and even from next-generation sequencing technology. Finally, we provide a molecular interpretation for the tissue and cell-type models as the biological basis for URSA’s classifications.
Availability and implementation: An interactive web interface for using URSA for gene expression analysis is available at: The source code is available at
Supplementary information: Supplementary data are available at Bioinformatics online.
PMCID: PMC3834796  PMID: 24037214
8.  Effectiveness of Retropubic Tension-Free Vaginal Tape and Transobturator Inside-Out Tape Procedures in Women With Overactive Bladder and Stress Urinary Incontinence 
We compared the effectiveness of the retropubic tension-free vaginal tape (TVT) and the transobturator inside-out tape (TVT-O) in treating symptoms of overactive bladder (OAB) in women with stress urinary incontinence (SUI).
Women with urodynamic SUI and OAB (mean urgency episodes ≥1 and frequency ≥8/24 hours on a 3-day voiding diary) were assigned to the TVT or TVT-O group. Preoperative measures were based on a urodynamic study, 3-day voiding diary, the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTSSF), and the urgency perception scale (UPS). At 12 postoperative months, the 3-day voiding diary, symptoms questionnaire, patient satisfaction, and standing stress test were assessed. The primary endpoint was change in the number of urgency episodes/24 hours from baseline to 12 months.
In this group of 132 women, 42 received TVT and 90 received TVT-O. The mean urgency episodes/24 hours decreased from 6.3±5.5 to 1.6±3.2 in the TVT group and from 5.1±4.4 to 1.8±3.0 in the TVT-O group. The mean percent change was significantly greater after TVT than after TVT-O (73% vs. 60%, P=0.049). All subscales of BFLUTSSF and UPS were significantly improved using either method, with significantly greater improvement seen in the quality of life (QoL) domain after TVT (P=0.002). There were no significant differences in the cure and satisfaction rates between the two groups.
Intervention with the TVT or the TVT-O significantly improved symptoms of OAB in women with SUI and OAB. Urgency and QoL significantly improved after TVT compared with that after TVT-O.
PMCID: PMC3797895  PMID: 24143294
Overactive urinary bladder; Stress urinary incontinence
9.  Transurethral Procedures for Lower Urinary Tract Symptoms Resulting From Benign Prostatic Enlargement: A Quality and Meta-Analysis 
Thanks to advancements in surgical techniques and instruments, many surgical modalities have been developed to replace transurethral resection of the prostate (TURP). However, TURP remains the gold standard for the surgical treatment of benign prostatic hyperplasia (BPH). We conducted a meta-analysis on the efficacy and safety of minimally invasive surgical therapies for BPH compared with TURP.
This meta-analysis used a Medline search assessing the period from 1997 to 2011. A total of 784 randomized controlled trials were identified in an electronic search. Among the 784 articles, 36 randomized controlled trials that provided the highest level of evidence (level 1b) were included in the meta-analysis. We also conducted a quality analysis of selected articles.
Only 2 articles (5.56%) were assessed as having a low risk of bias by use of the Cochrane collaboration risk of bias tool. On the other hand, by use of the Jadad scale, there were 26 high-quality articles (72.22%). Furthermore, 28 articles (77.78%) were assessed as high-quality articles by use of the van Tulder scale. Holmium laser enucleation of the prostate (HoLEP) showed the highest reduction of the International Prostate Symptom Score compared with TURP (P<0.0001). Bipolar TURP, bipolar transurethral vaporization of the prostate, HoLEP, and open prostatectomy showed superior outcome in postvoid residual urine volume and maximum flow rate. The intraoperative complications of the minimally invasive surgeries had no statistically significant inferior outcomes compared with TURP. Also, there were no statistically significant differences in any of the modalities compared with TURP.
The selection of an appropriate surgical modality for BPH should be assessed by fully understanding each patient's clinical conditions.
PMCID: PMC3713243  PMID: 23869269
Prostatic hyperplasia; Holmium; Lasers; Potassium titanylphosphate; Transurethral resection of prostate; Meta-analysis
10.  Chlamydia and Male Lower Urinary Tract Diseases 
Korean Journal of Urology  2013;54(2):73-77.
Of the chlamydia species that can cause infections in humans, C. trachomatis is responsible for lower urinary tract diseases in men and women. C. trachomatis infections are prevalent worldwide, but current research is focused on females, with the burden of disease and infertility sequelae considered to be a predominantly female problem. However, a role for this pathogen in the development of male urethritis, epididymitis, and orchitis is widely accepted. Also, it can cause complications such as chronic prostatitis and infertility. This review summarizes C. trachomatis infection in the male genitourinary tract, including urethritis, epididymitis, orchitis, and its complications, and addresses the microbiology, epidemiology, screening, clinical manifestations, diagnosis, and treatment.
PMCID: PMC3580308  PMID: 23550267
Chlamydia; Chronic prostatitis; Epididymitis; Infertility orchitis; Urethritis
11.  Vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma 
Anatomy & Cell Biology  2011;44(3):204-209.
A low serum level of vitamin D has been associated with an increased incidence of gastrointestinal tract cancers. However, the effects of vitamin D3 have not been investigated in gastric cancer and cholangiocarcinoma. In the present study, we found that vitamin D3 treatment significantly suppressed the viability of gastric cancer and cholangiocarcinoma cells. Moreover, vitamin D3 had a synergistic effect with other anti-cancer drugs, such as paclitaxel, adriamycin, and vinblastine, for suppressing cell viability. To determine the underlying mechanism involved in the regulation of viability by vitamin D3, we examined the effects of vitamin D3 on expression of hedgehog signaling target genes, which has been associated with gastric cancer and cholangiocarcinoma. Vitamin D3 treatment decreased the level of mRNA expression of patched1, Gli1, cyclin D1, and Bcl2, suggesting the possibility that vitamin D3 may act through regulation of hedgehog signaling. From the above results, we conclude that vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma.
PMCID: PMC3195824  PMID: 22025972
Cholecalciferol; Stomach neoplasms; Cholangiocarcinoma
12.  Prevalence and Treatment Efficacy of Genitourinary Mycoplasmas in Women with Overactive Bladder Symptoms 
Korean Journal of Urology  2010;51(9):625-630.
To evaluate the incidence of genitourinary mycoplasmas and the efficacy of antibiotics in women with overactive bladder (OAB) symptoms.
Materials and Methods
Women with OAB symptoms (micturition ≥8/24 hours and urgency ≥1/24 hours) for ≥3 months were screened for Mycoplasma hominis (M. hominis), Ureaplasma urealyticum (U. urealyticum), and Chlamydia trachomatis (C. trachomatis). Specimens from urethral and cervical vaginal swabs were examined for M. hominis and U. urealyticum by using the Mycoplasma IST2 kit and for C. trachomatis by using PCR. Women with positive results were treated with a 1 g dose of azithromycin. Persistent infection was treated with doxycycline. Changes in a 3-day bladder diary, Patient Perception of Bladder Condition (PPBC), and International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) were evaluated 4 weeks after negative conversion. Patient satisfaction was assessed.
Of 84 women screened, 42.8% were positive (U. urealyticum, 40.5%; M. hominis, 7.1%; C. trachomatis, 3.6%; two organisms, 8.3%). After treatment, 82.7% obtained negative conversion, and their median number of micturition episodes decreased from 10.6/24 hours to 8.1/24 hours (p=0.002). PPBC and domain scores of the ICIQ-FLUTS (filling and quality of life) significantly improved. About 87.5% women with negative conversion were satisfied with the treatment.
Considering diagnostic tests and treatment for genitourinary mycoplasmas might be beneficial before invasive workup or treatment in women with OAB symptoms.
PMCID: PMC2941811  PMID: 20856647
Chlamydia trachomatis; Mycoplasma hominis; Overactive urinary bladder; Ureaplasma urealyticum
13.  Randomized Comparative Study of the U- and H-Type Approaches of the TVT-Secur Procedure for the Treatment of Female Stress Urinary Incontinence: One-Year Follow-Up 
Korean Journal of Urology  2010;51(4):250-256.
We compared outcomes of the U- and H-type approaches of the tension-free vaginal tape (TVT)-Secur procedure for the treatment of female stress urinary incontinence (SUI).
Materials and Methods
From March 2007 to July 2008, 115 women with SUI underwent TVT-Secur by a single surgeon. Patients were randomly assigned to either the U- or the H-type approach. After 12 months, postoperative changes in the Sandvik questionnaire, incontinence quality of life questionnaire (I-QoL), Bristol female lower urinary tract symptoms-scored form (BFLUTS-SF), and postoperative patient satisfaction were evaluated. Cure was regarded as no leakage on the Sandvik questionnaire. Complications were also evaluated.
Of 115 women, 53 were treated with the U approach, and 62 women were treated with the H approach. At 12 months, 88.7% of those treated with the U approach and 87.1% of those treated with the H approach were cured (p=0.796). The I-QoL and filling, incontinence, sexual function, and QoL sum (BFLUTS-SF) scores were improved with both approaches, and there were no significant differences in the degree of improvement between approaches. Approximately 83.7% and 82.9% of the women treated with the U and H approaches, respectively, were satisfied with the outcome (p=0.858). There were 3 cases of intra-operative vaginal wall perforation in the H-type group. Immediate postoperative retention was observed in 2 women in the U-type group and 1 woman in the H-type group. One woman in the U-type group underwent tape releasing and cutting procedures for persistent large post-void residuals.
The U- and the H-type approaches of the TVT-Secur procedure provided comparable effectiveness for the treatment of female SUI.
PMCID: PMC2858851  PMID: 20428427
Comparative study; Stress urinary incontinence; Therapy
14.  The Evolution of Surgical Treatment for Female Stress Urinary Incontinence: Era of Mid-Urethral Slings 
Korean Journal of Urology  2010;51(4):223-232.
Based on the integral theory, tension-free placement of a mid-urethral sling (MUS) for female stress urinary incontinence (SUI) has gained substantial popularity owing to the ease of the procedure and its effectiveness. Published series with long-term follow-up show continence rates after the MUS procedure ranging from 70% to 80%. Complication rates after MUS procedures are usually low. This review aimed to describe the historical change and the current use of the MUS. We discuss the efficacy and complications of various MUS procedures and the current strategies for managing failed slings.
PMCID: PMC2858859  PMID: 20428423
Stress urinary incontinence; Tension-free vaginal tape; Trans-obturator tape
15.  Efficacy and Safety of "Tension-free" Placement of Gynemesh PS for the Treatment of Anterior Vaginal Wall Prolapse 
To evaluate the efficacy and safety of the tension-free placement of a monofilament polypropylene mesh for the repair of an anterior vaginal wall prolapse (AVWP).
Materials and Methods
Women aged ≥ 30 years with an AVWP stage of II or greater were included. Forty-nine women underwent trans-vaginal repair using a Gynemesh™ PS. Forty-six women who had symptomatic stress urinary incontinence received a midurethral sling (MUS). At the 12-month follow-up, evaluations were made for changes in the Pelvic Organ Prolapse Quantification (POP-Q) stage and Pelvic Floor Distress Inventory. Cure was defined as a POP-Q stage of 0 and improvement as a stage of I. Complications were also evaluated.
The cure rate was 71.4%, and the improvement rate was 18.4%. Obstructive/discomfort, irritative, and stress subscale scores of the Urinary Distress Inventory anterior and posterior subscale scores of the POP Distress Inventory and the obstructive subscale score of the Colo-Rectal-Anal Distress Inventory were significantly improved. Thirty-two of the 46 women (69.6%) who received MUS procedures reported no leakage after surgery. Complications were 2 cases of increased intraoperative bleeding and 1 case of vaginal erosion.
Trans-vaginal repair using a Gynemesh™ PS is a feasible and effective procedure for the treatment of AVWP with no significant complications.
PMCID: PMC2989483  PMID: 21120174
Pelvic organ prolapse; Lower urinary tract symptoms; Surgery
16.  Anatomical and Functional Outcomes of Posterior Intravaginal Slingplasty for the Treatment of Vaginal Vault or Uterine Prolapse: A Prospective, Multicenter Study 
Korean Journal of Urology  2010;51(3):187-192.
We aimed to evaluate the anatomical and functional outcomes of posterior intravaginal slingplasty (P-IVS) for the treatment of a vaginal vault or uterine prolapse (VP/UP).
Materials and Methods
This was a 12-month prospective, multicenter, observational study. Women aged over 30 years who presented with stage II or greater VP/UP underwent P-IVS by four urologists at four university hospitals. Preoperatively, pelvic examination by use of the Pelvic Organ Prolapse Quantification (POP-Q) system, the Pelvic Floor Distress Inventory (PFDI) questionnaire, the 3-day frequency volume chart, and uroflowmetry were completed. At the 12-month follow-up, changes in the POP-Q, PFDI, frequency volume chart, and uroflowmetry parameters were assessed. Cure was defined as VP/UP stage 0 and improvement as stage I.
The cure and improvement rates among the 32 women were 65.6% and 34.4%, respectively. All subscale scores of the Urinary Distress Inventory, the general subscale score of the Pelvic Organ Prolapse Distress Inventory, and the rectal prolapse subscale score of the Colo-Rectal-Anal Distress Inventory were significantly improved. There were no significant changes in the frequency volume chart or uroflowmetry parameters. There was one case of surgery-related transfusion.
Trans-vaginal repair by P-IVS is an effective and safe procedure for restoring the anatomical defect and improving the associated pelvic floor symptoms in women with VP/UP.
PMCID: PMC2855447  PMID: 20414395
Prospective studies; Treatment outcome; Pelvic organ prolapse
17.  Efficacy and Safety of Tamsulosin for the Treatment of Non-neurogenic Voiding Dysfunction in Females: A 8-Week Prospective Study 
Journal of Korean Medical Science  2009;25(1):117-122.
We evaluated the therapeutic effects of tamsulosin for women with non-neurogenic voiding dysfunction. Women who had voiding dysfunctions for at least 3 months were included. Inclusion criteria were age ≥18 yr, International Prostate Symptom Score (IPSS) of ≥15, and maximum flow rate (Qmax) of ≥12 mL/sec and/or postvoid residuals (PVR) of ≥150 mL. Patients with neurogenic voiding dysfunction or anatomical bladder outlet obstruction were excluded. All patients were classified according to the Blaivas-Groutz nomogram as having no or mild obstruction (group A) or moderate or severe obstruction (group B). After 8 weeks of treatment, treatment outcomes and adverse effects were evaluated. One hundred and six patients were evaluable (70 in group A, 36 in group B). After treatments, mean IPSS, bother scores, Qmax, PVR, diurnal and nocturnal micturition frequencies and scored form of the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTS-SF) were changed significantly. Eighty-nine patients (84%) reported that the treatment was beneficial. The proportion of patients reported that their bladder symptoms caused "moderate to many severe problems" were significantly decreased. No significant difference were observed between the groups in terms of IPSS, bother score, Qmax, PVR, micturition frequency, and BFLUTS-SF changes. Adverse effects related to medication were dizziness (n=3), de novo stress urinary incontinence (SUI) (n=3), aggravation of underlying SUI (n=1), fatigue (n=1). Tamsulosin was found to be effective in female patients with voiding dysfunction regardless of obstruction grade.
PMCID: PMC2800025  PMID: 20052356
Urination Disorders; Female; Adrenergic alpha-Antagonists; Outcomes Assessment
18.  Regulation of cerebrospinal fluid production by caffeine consumption 
BMC Neuroscience  2009;10:110.
Caffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date.
In the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na+, K+-ATPase and increased cerebral blood flow (CBF). In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A1 adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na+, K+-ATPase, in A1 agonist-treated rats.
The results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na+, K+-ATPase and CBF.
PMCID: PMC2744679  PMID: 19725982
19.  Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2 
Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2.
PMCID: PMC2738910  PMID: 19742123
gastric cancer; hedgehog signaling; apoptosis; Bcl-2
20.  Forkhead box O-class 1 and Forkhead box G1 as Prognostic Markers for Bladder Cancer 
Journal of Korean Medical Science  2009;24(3):468-473.
Forkhead box O-class 1 (FOXO1) is a key regulator of glucose homeostasis, cell-cycle progression, and apoptosis. Its functions are modulated by forkhead box G1 (FOXG1), which acts as a transcriptional repressor with oncogenic potential. Real-time PCR and immunohistochemical staining were performed in 174 primary bladder cancer specimens and 21 normal bladder mucosae to evaluate these genes. FOXO1 and FOXG1 mRNA expression in cancer tissues were higher than in normal mucosae (each P<0.001). FOXO1 mRNA levels were significantly higher in samples of non-progressed patients (P<0.001), but FOXG1 were enhanced in those of progressed patients (P=0.019). On univariate analysis, FOXO1 mRNA expression was significantly associated with grade, stage, recurrence, progression and survival (each P<0.05). On multivariate analysis, increased FOXO1 mRNA expression was associated with both reduced disease progression (odds ratio [OR], 0.367; 95% confidence interval [CI], 0.163-0.826, P=0.015) and enhanced disease-free survival (OR, 3.262; 95% CI, 1.361-7.820, P=0.008). At a median follow-up of 33 months (range 2 to 156), the patients with a high FOXO1 mRNA expression had a significantly prolonged survival (P=0.001). Immunohistochemical findings of FOXO1 were generally concordant with mRNA expression levels. In conclusion, FOXO1 may be a promising marker for predicting progression in human bladder cancers.
PMCID: PMC2698194  PMID: 19543511
FOXO1; FOXG1; Urinary Bladder Neoplasms; Prognostic Factor; Real Time PCR; Immunohistochemistry
21.  Eosinophilic Granuloma Presenting as an Epidural Hematoma and Cyst 
Langerhans' cell histiocytosis (LCH) is a rare immunologic disorder characterized by histiocyte proliferation in multiple organ systems. Eosinophilic granuloma, a benign bone lesion, represents a focal form of LCH. We experienced a case of Langerhans' cell histiocytosis in a patient who presented with intracranial epidural hematoma and cyst on the midline of the frontal skull. A 10-year-old boy presented with a rapidly growing large scalp mass on the midline frontal area after mild head trauma. The scalp mass was painless and immobile. Plain skull x-ray showed a punched-out bone lesion. Computed tomography and magnetic resonance imaging showed a non-enhancing osteolytic lesion presenting with an epidural hematoma and cyst on the midline of the frontal skull. The lesion of the skull was completely resected and the patient's recovery was uneventful. The acute presentation of a solitary eosinophilic granuloma of skull with an epidural hematoma has been described in only five cases in the literature and we report the first case of LCH presenting as an intracranial epidural hematoma on frontal area.
PMCID: PMC2588256  PMID: 19096637
Langerhans' cell histiocytosis; Epidural hematoma; Eosinophilic granuloma; Head trauma
22.  Decreased Hepatic Nerve Fiber Innervation in Patients with Liver Cirrhosis 
Gut and Liver  2007;1(2):165-170.
Hepatic nerve innervation plays important roles in hepatic metabolism and hemodynamic mechanisms. We compared the distribution patterns of hepatic nerves between normal livers and two liver diseases to elucidate the effects of liver disease on the distribution of hepatic nerves.
Tissue specimens were obtained by ultrasonography-guided needle biopsies from 10 normal controls, 74 patients with chronic hepatitis (CH), and 35 patients with liver cirrhosis (LC). The obtained specimens were immunohistochemically stained using antibodies for S-100 protein and α-smooth-muscle actin (α-SMA). The degree of the expression in liver tissues was quantified by manual counting of positively stained nerve fibers under light microscopy. The serum hyaluronic acid level was assayed in all subjects to evaluate hepatic fibrosis. Electron microscopy examinations were also performed.
The hepatic nerve innervation was significantly lower in LC than in normal controls, as indicated by S-100 protein staining. α-SMA and hyaluronic acid levels were higher in LC and CH than in normal controls. Electron microscopy revealed that unmyelinated nerve fiber bundles in the intralobar connective tissue coursed in the vicinity of hepatic triads.
These results suggest that hepatic nerve innervation can be decreased by hepatic inflammatory responses and/or fibrotic changes in LC patients. Further study is needed to clarify this observation.
PMCID: PMC2871629  PMID: 20485634
α-SMA; Electron microscopy; Hepatic nerve innervation; Hyaluronic acid; S-100
23.  Clinical Outcomes of Delayed Clearance of Serum HBsAg in Patients with Chronic HBV Infection 
Spontaneous delayed clearance of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection is a rare event. The aim of this study was to investigate the incidence of delayed clearance of serum HBsAg in chronic HBV infection and to determine the characteristics and clinical outcomes of HBsAg delayed clearance in Korean patients.
From April 1981 to June 2003, 4,061 patients who were positive for HBsAg were evaluated retrospectively. The following assessments were undertaken in 47 patients who had spontaneous delayed clearance: liver biochemistry, viral markers, α-fetoprotein levels, and radiographic examinations including ultrasonography every three to six months for 6-264 months (median 87.9 months).
Twenty-four of 47 patients were asymptomatic carriers. The others included seven patients with chronic hepatitis, seven with liver cirrhosis and nine with hepatocellular carcinoma. The estimated annual incidence of HBsAg seroclearance was 0.4%. The time span from positive HBsAg to HBsAg seroclearance in the AHC, CH, LC, and HCC was 62.9, 141, 63, and 95.3 months during follow up. Twenty-four of 24 AHC remained normal, 5 of 7 CH remained as CH and 2 patients remained normal, 1 of 7 with LC developed HCC and 6 of the LC remained as LC, and 4 of 9 HCC patients died.
The clinical course following delayed clearance of HBsAg had diverse outcomes from AHC to HCC. Therefore, these patients require close follow up for the possible development of hepatocellular carcinoma following HBsAg clearance.
PMCID: PMC2687613  PMID: 17616021
Hepatitis B virus; Hepatitis B surface antigen; Seroclearance
24.  Usefulness of MR Imaging for Diseases of the Small Intestine: Comparison with CT 
Korean Journal of Radiology  2000;1(1):43-50.
To evaluate the usefulness of MR imaging for diseases of the small intestine, emphasizing a comparison with CT.
Materials and Methods
Thirty-four patients who underwent both CT and MR imaging using FLASH 2D and HASTE sequences were analyzed. All patients had various small bowel diseases with variable association of peritoneal lesions. We compared the detectabilities of CT and MR imaging using different MR pulse sequences. The capability for analyzing the characteristics of small intestinal disease was also compared.
MR imaging was nearly equal to CT for detecting intraluminal or peritoneal masses, lesions in the bowel and mesentery, and small bowel obstruction, but was definitely inferior for detecting omental lesions. The most successful MR imaging sequence was HASTE for demonstrating bowel wall thickening, coronal FLASH 2D for mesenteric lesions, and axial FLASH 2D for omental lesions. MR imaging yielded greater information than CT in six of 12 inflammatory bowel diseases, while it was equal to CT in six of seven neoplasms and inferior in five of seven mesenteric ischemia. In determining the primary causes of 15 intestinal obstructions, MR imaging was correct in 11 (73%) and CT in nine (60%) patients.
MR imaging can serve as an alternative diagnostic tool for patients with suspected inflammatory bowel disease, small intestinal neoplasm or obstruction.
PMCID: PMC2718137  PMID: 11752928
Gastrointestinal tract, diseases; Gastrointestinal tract, MR; Gastrointestinal tract, CT; Magnetic resonance (MR), comparative studies

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