Publications (20)60.7 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Confocal laser endomicroscopy (CLE) is a new technology enabling endoscopists to visualize tissue at the cellular level. CLE has the fundamental potential to provide a histologic diagnosis, and may theoretically replace or reduce the need for performing biopsy for histology. The clinical benefits of CLE are more obvious in esophageal disease, including Barrett's esophagus. Currently, this technology has been adapted to the diagnosis and surveillance of Barrett's esophagus and related neoplasia. Standard white light endoscopy is the primary tool for gastric cancer screening. Currently, the only method available to precisely diagnose these lesions is upper endoscopy with an appropriate biopsy. A recent study showed that CLE could characterize dysplasia or cancer and identify the risk factors for gastric cancer, such as intestinal metaplasia and the presence of Helicobacter pylori in vivo, although fewer studies on CLE were performed on the stomach than on Barrett's esophagus and other esophageal diseases. However, the application of CLE to routine clinical endoscopy continues to be refined. This review focused on the usefulness and future prospects of CLE for gastric premalignant and malignant lesions.
- [Show abstract] [Hide abstract] ABSTRACT: Although serum pepsinogen tests are useful for predicting the presence of atrophic gastritis, the optimal cut-off values have not been fully evaluated. To determine the optimal serum pepsinogen cut-off value for predicting atrophic gastritis. Patients scheduled for upper endoscopy at Severance Hospital, Korea, between August 2012 and October 2013, were recruited prospectively. Endoscopic biopsies for atrophic gastritis were obtained and histologically graded, based on the updated Sydney system. Ninety-five patients were enrolled in the study. The mean age was 57.7±12.1 years, and 44.2% of the patients were male. Serum pepsinogen I/II ratios were lower in patients with atrophic gastritis than in those without it (antrum, 4.2±1.7 vs. 5.2±2.1, P=0.040; corpus, 3.3±1.9 vs. 5.4±1.9, P<0.001). Serum pepsinogen I/II ratios were significantly correlated with histologic atrophic gastritis (antrum, P=0.030; corpus, P<0.001). Using a cut-off value of 4.9, the sensitivity and specificity of the serum pepsinogen I/II ratio for predicting atrophic gastritis in the antrum were 68.2% and 60.3%, respectively. The optimal serum pepsinogen I/II ratio cut-off values for atrophic gastritis of the antrum and for the corpus were 4.9 and 3.5, respectively. Serum pepsinogen I/II ratios, with these cut-off values, are useful for screening patients for the presence of atrophic gastritis. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: Background Erosive esophagitis and fatty liver share obesity and visceral fat as common critical pathogenesis. However, the relationship between the amount of hepatic fat and the severity of erosive esophagitis was not well investigated, and there is no risk estimation model for erosive esophagitis. Aim To evaluate the relationship between the amount of hepatic fat and the severity of erosive esophagitis and then develop a risk estimation model for erosive esophagitis. Methods We enrolled 1045 consecutive participants (training cohort, n = 705; validation cohort, n = 340) who underwent esophagogastroduodenoscopy and CAP. The relationship between severity of fatty liver and erosive esophagitis was investigated, and independent predictors for erosive esophagitis that have been investigated through logistic regression analyses were used as components for establishing a risk estimation model. Results The prevalence of erosive gastritis was 10.7 %, and the severity of erosive esophagitis was positively correlated with the degree of hepatic fatty accumulation (P < 0.05). A CAP-based risk estimation model for erosive esophagitis using CAP, Body mass index, and significant alcohol Drinking as constituent variables was established and was dubbed the CBD score (AUROC = 0.819, range 0–11). The high-risk group (CBD score ≥3) showed significantly higher risk of having erosive esophagitis than the low-risk group (CBD score <3) (24.1 vs. 2.7 %, respectively; P < 0.001). The diagnostic accuracy of CBD score was maintained in the validation cohort (AUROC = 0.848). Conclusion The severity of erosive esophagitis was positively correlated with the degree of hepatic fatty accumulation, and the CBD score might be a simple CAP-based risk model for predicting erosive esophagitis.
- [Show abstract] [Hide abstract] ABSTRACT: We have investigated basic properties of normal gastrointestinal (GI) tract tissues, including glandular stomach (GS), fore stomach (FS), large intestine (LI), small intestine (SI), and esophagus (ESO), from a rat model using terahertz (THz) reflection imaging and spectroscopy. The THz images collected from stratified squamous epithelia (SSE) of FS and ESO show a lower peak-to-peak value compared to those from columnar epithelia (CE) of GS, LI, or SI because the SSE contains less water than CE. The refractive index and absorption coefficient of FS were less than those of GS or LI, both having values similar to those of water. Additionally, we report internal reflection THz signals from ESO, although we were unable to determine the exact interface for this internal reflection.
- [Show abstract] [Hide abstract] ABSTRACT: Although endoscopic submucosal dissection (ESD) is now accepted for treatment of early gastric cancers (EGC) with negligible risk of lymph node (LN) metastasis, ESD for intramucosal undifferentiated type EGC without ulceration and with diameter ≤ 2 cm is regarded as an investigational treatment according to the Japanese gastric cancer treatment guidelines. This consideration was largely based on the analysis of surgically resected EGCs that contained undifferentiated type EGCs; however, results from several institutes showed some discrepancies in sample size and incidence of LN metastasis. Recently, some reports about the safety and efficacy of ESD for undifferentiated type EGC meeting the expanded criteria have been published. Nonetheless, only limited data are available regarding long-term outcomes of ESD for EGC with undifferentiated histology so far. At the same time, endoscopists cannot ignore the patients' desire to guarantee quality of life after the relatively non-invasive endoscopic treatment when compared to conventional surgery. To satisfy the needs of patients and provide solid evidence to support ESD for undifferentiated EGC, we need more delicate tools to predict undetected LN metastasis and more data that can reveal predictive factors for LN metastasis.
- [Show abstract] [Hide abstract] ABSTRACT: Intestinal metaplasia (IM), a premalignant lesion, is associated with an increased risk of gastric cancer. Although estrogen exposure, including tamoxifen, has been studied in correlation with gastric cancer, little has been investigated about its effects on IM. Therefore, we investigated whether chronic tamoxifen use was associated with the risk of IM in human stomach. We evaluated 512 gastric biopsies from 433 female breast cancer patients that underwent endoscopic gastroduodenoscopy (EGD) ≥6 months after breast surgery. Histopathological findings were scored according to the updated Sydney classification. Demographic and clinical characteristics were also included to identify predictive factors for IM. In a multivariate logistic regression analysis, age at EGD (odds ratio [OR], 1.04; P = 0.002), biopsies from antrum (OR 2.08; P < 0.001), and Helicobacter pylori positivity (OR 1.68; P = 0.016) were significantly associated with an increased risk of IM, whereas chronic tamoxifen use (≥3 months) was associated with a decreased risk of IM (OR 0.59; P = 0.025). After stratifying by biopsy site, association between tamoxifen use and IM persisted for corpus (OR 0.42; P = 0.026) but not for antrum (OR 0.74; P = 0.327). In analysis limited to patients with follow-up EGD, chronic tamoxifen use also correlated with improved IM score compared to no tamoxifen use (improved, 77.8 vs. 22.2 %; no change, 65.4 vs. 34.6 %; worsened, 30.0 vs. 70.0 %; P = 0.019). This study suggests that chronic tamoxifen use can decrease the risk of IM in human stomach. The effect of tamoxifen is predominantly observed in the corpus.
- [Show abstract] [Hide abstract] ABSTRACT: Circadian rhythm is a fundamental biological system involved in the regulation of various physiological functions. However, little is known about a nature or function of circadian clock in human primary cells. In the present study, we have applied in vitro real time circadian rhythm monitoring to study human clock properties using primary skin fibroblasts. Among factors that affect human physiology, slightly lower extracellular pH was chosen to test its effects on circadian rhythm expression. We established human primary fibroblast cultures obtained from three healthy subjects, stably delivered a circadian reporter gene Bmal1-luciferase, and recorded circadian rhythms in the culture medium at pH 7.2 and 6.7. At pH 7.2, robust and sustained circadian rhythms were observed with average period length 24.47 ± 0.03 h. Such rhythms were also found at pH 6.7; however, period length was significantly shortened to 22.60 ± 0.20, amplitude was increased, and damping rate was decreased. The effect of exposure to low pH on the period length was reversible. The shortened period was unlikely caused by factors affecting cell viability because cell morphology and MTT assay showed no significant difference between the two conditions. In summary, our results showed that the circadian rhythm expression is affected at pH 6.7 in human primary fibroblasts without affecting cell viability.
- [Show abstract] [Hide abstract] ABSTRACT: We developed an ultra-low field (ULF)-nuclear magnetic resonance (NMR) measurement system capable of working with a measurement field (Bm) of several micro-tesla and performed basic NMR studies with a double relaxation oscillation superconducting quantum interference device (DROS) instead of conventional dc-SQUIDs. DROS is a SQUID sensor utilizing a relaxation oscillation between a dc-SQUID and a relaxation circuit; the new unit consists of an inductor and a resistor, and is connected in parallel with the SQUID. DROS has a 10 times larger flux-to-voltage transfer coefficient (∼mV/ϕ0) than that of the dc-SQUID, and this large transfer coefficient enables the acquisition of the SQUID signal with a simple flux-locked-loop (FLL) circuit using room temperature pre-amplifiers. The DROS second-order gradiometer showed average field noise of 9.2 μϕ0/√Hz in a magnetically shielded room (MSR). In addition, a current limiter formed of a Josephson junction array was put in a flux-transformer of DROS to prevent excessive currents that can be generated from the high pre-polarization field (Bp). Using this system, we measured an 1H NMR signal in water under 2.8 μT Bm field and reconstructed a one-dimensional MR image from the 1H NMR signal under a gradient field BG of 4.09 nT/mm. In addition, we confirmed that the ULF-NMR system can measure the NMR signal in the presence of metal without any distortion by measuring the NMR signal of a sample wrapped with metal. Lastly, we have measured the scalar J-coupling of trimethylphosphate and were able to confirm a clear doublet NMR signal with the coupling strength J3[P,H] = 10.4 ± 0.8 Hz. Finally, because the existing ULF-NMR/MRI studies were almost all performed with dc-SQUID based systems, we constructed a dc-SQUID-based ULF-NMR system in addition to the DROS based system and compared the characteristics of the two different systems by operating the two systems under identical experimental conditions.
- [Show abstract] [Hide abstract] ABSTRACT: Over the last decade, a growing number of non-coding transcripts have been found to have roles in gene regulation and RNA processing. The most well known small non-coding RNAs (ncRNAs) are the microRNAs (miRNAs), but the network of long and short non-coding transcripts is complex and is likely to contain as yet unidentified classes of molecules that form transcriptional regulatory networks. miRNAs and some other ncRNAs have been found to be involved in human tumorigenesis, revealing a new layer in the molecular architecture of cancer. Gene expression studies have shown that hundreds of miRNAs are deregulated in cancer cells, and functional studies have clarified that miRNAs are involved in all the molecular and biologic processes that drive tumorigenesis. Here, we summarize the recent advances in understanding miRNAs' and other ncRNAs' involvement in cancer and illustrate how this knowledge may be useful in medical practice. New diagnostic classifiers based on miRNAs will soon be available for medical practitioners, and even more importantly, miRNAs may become novel anti-cancer therapies.
- [Show abstract] [Hide abstract] ABSTRACT: Synthetic RNA-based regulatory systems are used to program higher-level biological functions that could be exploited, among many applications, for in vivo diagnostic and therapeutic applications. Chen and colleagues have recently reported a significant technological advance by producing an RNA modular device based on a hammerhead ribozyme and successfully tested its ability to control the proliferation of mammalian T lymphocytes. Like all exciting research, this work raises a lot of significant questions. How quickly will such knowledge be translated into clinical practice? How efficient will this system be in human clinical trials involving adaptive T-cell therapy? We discuss the possible advantages of using such new technologies for specific therapeutic applications.
- [Show abstract] [Hide abstract] ABSTRACT: Nitric oxide (NO) may aggravate neuronal damage after spinal cord injury (SCI). We hypothesized that NO produced by inducible nitric oxide synthase (iNOS) accelerates secondary damage to spinal tissue, which may be reversed by the neuroprotectant, melatonin. This study investigated the effects of combination therapy with melatonin (10 mg/kg) and exercise (10 m/min) on recovery from SCI caused by contusion. We examined locomotor recovery, iNOS gene expression, autophagic and apoptotic signaling, including Beclin-1, LC3, p53 and IKKalpha protein expression and histological alterations in the ventral horn of the spinal cord. Melatonin in combination with exercise resulted in significantly increased hindlimb movement (P < 0.05), a reduced level of iNOS mRNA (P < 0.05) and more motor neurons in the ventral horn, versus control SCI and SCI plus exercise alone, with no effect on the other signaling molecules examined. This study shows that combined therapy with melatonin and exercise reduces the degree of secondary damage associated with SCI in rats and supports the possible use of melatonin in combination with exercise to reduce the side effects related to exercise-induced fatigue and impairment.
- [Show abstract] [Hide abstract] ABSTRACT: Olmesartan medoxomil (OLM) is an antihypertensive angiotensin II receptor blocker. OLM has a low bioavailability (BA), approximately 26% in humans, due to its low water solubility and efflux by drug resistance pumps in the gastrointestinal tract. Self-microemulsifying drug delivery system (SMEDDS), which is easily emulsified in aqueous media under gentle agitation and digestive motility, was formulated to increase the oral BA of OLM. Among the surfactants and oils studied, Capryol 90, Tween 20, and Tetraglycol were chosen and combined at a volume ratio of 1:6:3 on the basis of equilibrium solubility and phase diagram experiments. The mean droplet size of SMEDDS was 15 nm. In an oral absorption study in rats, SMEDDS formulation brought faster absorption compared to suspension, showing a T max value of 0.2 hr. The C max and AUC values of SMEDDS formulation were significantly higher than those of suspension, revealing a relative BA of about 170%. Our study demonstrated the potential usefulness of SMEDDS for the oral delivery of poorly absorbable compounds, including OLM.
- [Show abstract] [Hide abstract] ABSTRACT: The feasibility of the enhanced immunization with diphtheria toxoid-loaded bioerodible microspheres was examined by investigating the serum antibody levels and lethal test in vivo. PLGA polymer was selected based on the properties such as degradability, tissue compatibility, and ease of particulate preparation. The double emulsion solvent extraction method was employed for the fabrication of microspheres to control the release of diphtheria toxoid. Dichloromethane or ethyl acetate was applied as an organic phase and poly (vinyl alcohol) as a secondary emulsion stabilizer during fabrication procedure. Diphtheria toxoid can be microencapsulated using PLGA copolymer without a loss of its immunogenicity. The results from the in vivo study with bioerodible microsphere indicated that the immunogenic response, expressed as ELISA IgG titers, was significantly higher than the conventional antigen for 8 weeks after single injection. Consequently, these microspheres could provide the controlled release of antigens for developing enhanced vaccine formulations as a parenteral carrier system.
- [Show abstract] [Hide abstract] ABSTRACT: Self-expanding metal stent has emerged as an effective treatment option for malignant gastroesophageal junction obstruction. However, data on the clinicopathologic factors associated with stent patency are still lacking. To investigate the long-term clinical outcomes and prognostic factors, including treatment modalities, affecting stent patency in patients with malignant gastroesophageal junction obstruction given self-expanding metal stent insertions. A total 89 patients who underwent self-expanding metal stent insertion for malignant gastroesophageal junction obstruction were enrolled. We analysed technical and clinical success rates, complications, and prognostic factors affecting stent patency. Self-expanding metal stent insertion was successful in all patients and clinical improvement was achieved in 93.3%. Stent malfunction occurred in 32.9% of patients. The median overall survival time and stent patency time were 143 (95% CI: 99-187) and 190 days (95% CI: 108-272), respectively. In multivariate analysis, radiation therapy after stent placement significantly prolonged stent patency (OR: 0.221; 95% CI: 0.055-0.884; p=0.033). A higher migration rate was observed in those patients given chemotherapy after covered self-expanding metal stent placement (no anticancer treatment: 10.0%, chemotherapy: 42.9%, chemoradiation therapy: 9.1%, p=0.042). Self-expanding metal stent is a feasible and effective treatment for malignant gastroesophageal junction obstruction. Radiation therapy after stent placement significantly prolongs overall stent patency and chemotherapy increases the migration rate of covered stents.
- [Show abstract] [Hide abstract] ABSTRACT: This study examined the relationships between family systems and high school students’ career development. Family adaptability and family cohesion were considered as indicators of family function, and career attitude maturity was conceptualized as a representative factor explaining adolescents’ career development. A total of 634 high school students participated in this study. Overall, the results showed that family adaptability and family cohesion were both significant predictors of tenth graders’ career attitude maturity. The effects of parents’ educational backgrounds on career attitude maturity were negligible. However, the relationships were inconsistent across gender. For female students, family cohesion was a more influential predictor of career attitude maturity than family adaptability, while the opposite pattern was observed for the male students. KeywordsFamily systems-Family adaptability-Family cohesion-Career attitude maturity
- [Show abstract] [Hide abstract] ABSTRACT: Genistein (GT) is an isoflavone from Leguminosae and has received much attention as a phytoestrogen. Genistin is a glycoside form of GT (genistein-7-O-beta-D-glucopyranoside, GT-glu) is mainly found in soy-derived foods. In this study, we examined the pharmacokinetic properties and bioavailability of GT in rats and compared with those of GT-glu. In order to characterize and compare the pharmacokinetics of GT and GT-glu, these compounds were administered intravenously and orally. The plasma concentration of GT was determined by HPLC after enzymatic hydrolysis. After oral administration of GT with various doses (4, 20, 40 mg/kg), the bioavailability of GT was 38.58, 24.34 and 30.75%, respectively. The T(max), C(max) and AUC(0-infinity) of GT after oral administration of GT (40 mg/kg), were 2h, 4876.19 ng/ml, 31,269.66 ng h/ml, respectively. When smaller amount of GT was administered, the faster T(max) was observed. Oral administration of GT-glu resulted in longer T(max), lower C(max), and greater bioavailability than that of GT. The pharmacokinetic parameters of GT following oral administration of GT-glu (64 mg/kg as GT-glu, 40 mg/kg as GT) were obtained as follows: 8h (T(max)), 3763.96 ng/ml (C(max)), 51,221.08 ng h/ml (AUC(0-infinity)) and 48.66% (absolute bioavailability), respectively. These results indicate that the oral bioavailability of GT-glu is greater than that of GT.
- [Show abstract] [Hide abstract] ABSTRACT: The impact of storage conditions on the permeability of porcine buccal mucosa to [3H]water and [14C]mannitol was assessed. The fresh porcine buccal tissue (fresh tissue) was obtained by utilizing pig heads within 24 hours of slaughter. The stored and frozen porcine buccal tissues (stored tissue and frozen tissue) were obtained after the storage of the tissue intact in the pig heads at 4 degrees C or -20 degrees C, respectively, for 24 h. The results demonstrated that the barrier properties of the porcine buccal mucosa were maintained with regard to [3H]water permeability when stored at 4 degrees C for 24 h. However, freezing the tissue resulted in tissue damage illustrated by a significant increase in [3H]water permeability. [14C]Mannitol does not appear to be a suitable model solute to assess the ex vivo permeability of porcine buccal mucosa due to its extremely low permeability.
Wonju Severance Christian HospitalGenshū, Gangwon-do, South Korea
Korea Research Institute of Standards and Science
Sŏul, Seoul, South Korea
- Brain and Cognition Measurement Center
Kŭmhae, South Gyeongsang, South Korea
- • College of Biomedical Science and Engineering
- • Department of Pharmaceutical Engineering
Yonsei University Hospital
Sŏul, Seoul, South Korea
- Department of Internal Medicine