[Show abstract][Hide abstract] ABSTRACT: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial.
Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders.
The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups.
The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
Clinical and molecular hepatology. 12/2014; 20(4):376-83.
[Show abstract][Hide abstract] ABSTRACT: Natural killer (NK) cells are innate immune effector cells that protect against cancer and some viral infections. Until recently, most studies have investigated the molecular signatures of human or mouse NK cells to identify genes that are specifically expressed during NK cell development. However, the mechanism regulating NK cell development remains unclear. Here, we report a regulatory network of potential interactions during in vitro differentiation of human NK cells, identified using genome-wide mRNA and miRNA databases through hierarchical clustering analysis, gene ontology analysis and a miRNA target prediction program. The microRNA (miR)-583, which demonstrated the largest ratio change in mature NK cells, was highly correlated with IL2 receptor gamma (IL2Rγ) expression. The overexpression of miR-583 had an inhibitory effect on NK cell differentiation. In a reporter assay, the suppressive effect of miR-583 was ablated by mutating the putative miR-583 binding site of the IL2Rγ 3' UTR. Therefore, we show that miR-583 acts as a negative regulator of NK cell differentiation by silencing IL2Rγ. Additionally, we provide a comprehensive database of genome-wide mRNA and miRNA expression during human NK cell differentiation, offering a better understanding of basic human NK cell biology for the application of human NK cells in immunotherapy.
PLoS ONE 10/2014; 9(10):e108913. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alimentary tract duplications are uncommon congenital abnormalities that usually have an anatomical connection with some part of the gastrointestinal tract and have a common blood supply with the adjacent segment of intestine. A completely isolated duplication cyst (CIDC) is a very rare type of gastrointestinal duplication that does not communicate with the normal bowel segment and possesses its own exclusive blood supply. Only 5 CIDC cases in adults have been reported in the English medical literature. Additionally, only 1 case of mucinous cystadenoma from an infected CIDC of the ileum has been reported. This report describes a 52-year-old male patient with a peritoneal CIDC, which upon curative excision was found to have given rise to an adenocarcinoma. The latter was lined internally with malignant glandular cells and contained a smooth muscular outer layer as determined by microscopic examination of the tissue. We believe that this is the first reported case of an adenocarcinoma originating from a CIDC in an adult.
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to identify microRNAs (miRNAs) that are differentially expressed in Helicobacter pylori-infected patients with an intestinal type of gastric cancer using miRNA microarray and to confirm the candidate miRNA expression levels.
[Show abstract][Hide abstract] ABSTRACT: For tympanoplasty, the most common grafting materials are the temporalis fascia or perichondrium; however, both require incision of the canal skin, which carries a risk of morbidity and the need for postoperative care. Inlay butterfly cartilage tympanoplasty, by which the perforation edges are refreshed and a cartilage is inserted through the perforation without canal incision, makes the graft easy, and reduces operating and recovery time. We analyze the outcome of inlay butterfly cartilage tympanoplasty.
[Show abstract][Hide abstract] ABSTRACT: Hepatic stellate cells (HSCs) activation is a crucial step in the pathogenesis of hepatic fibrosis. Histone deacetylase (HDAC) is an attractive target in liver fibrosis because it plays a key role in gene expression and cell differentiation. We have developed a HDACI, N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and investigated the antifibrotic activity of HNHA in vitro and in vivo.
We investigate the anti-fibrotic effect of a HNHA, on mouse and human HSC (hepatic stellate cell) activation in vitro and on liver of bile duct ligated (BDL) rat in vivo using cell proliferation assays, cell cycle analysis, biochemical assay, immunohistochemistry, or western blotting. Liver histopathology was analyzed with hematoxylin-eosin and Masson's trichrome staining.
HNHA inhibited proliferation and arrested the cell cycle via p21 induction in HSCs. In addition, HNHA led to apoptosis of HSCs, which was correlated with reduced COX-2 expression and increased the phosphorylation of IkB-α and cell death signals. HNHA recovered liver function and noticeably decreased excessive accumulation of extracellular matrix in liver via suppression of HSC activation on the BDL in vivo. In addition, HNHA administration increased as life span of BDL rat.
HNHA improved liver function, suppressed liver fibrosis, and prolonged the life span of BDL rats, which was accompanied by noticeable reductions of cell growth, activation, and survival of HSCs. These findings show that HNHA may be a potent anti-fibrosis agent against hepatic fibrosis due to its multi-targeted inhibition of HSC activity in vivo and in vitro.
British Journal of Pharmacology 01/2014; · 5.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis.
LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG ≥10 and ≥12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves.
A strong positive correlation between LSM and HVPG was observed in the overall population (r(2)=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG ≥10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG ≥12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively.
LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.
Clinical and molecular hepatology. 12/2013; 19(4):370-5.
[Show abstract][Hide abstract] ABSTRACT: We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis.
Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated.
The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4.
The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.
Clinical and molecular hepatology. 12/2013; 19(4):389-98.
[Show abstract][Hide abstract] ABSTRACT: Asthma is an inflammatory disease of the lung that is characterized by airway hyperresponsiveness and the increase of inflammatory cell infiltration into the airways. Naturally occurring flavones have potent anti-inflammatory effects, but their effects on asthmatic responses are still relatively unknown.
We evaluated the inhibitory effects of flavone derivatives having the chromone moiety on the immediate-phase asthmatic response (IAR) and the late-phase asthmatic response (LAR) to aerosolized-ovalbumin (OA) exposure in conscious OA-sensitized guinea pigs.
Luteolin and apigenin (30 mg/kg, p.o.) significantly (P < 0.05) decreased not only the specific airway resistance (sRaw) in IAR and LAR, but also the recruitment of leukocytes and the release of histamine and activities of phospholipase A2 (PLA2) and eosinophil peroxide (EPO) in bronchoalveolar lavage fluid (BALF), compared to control. However, their anti-asthmatic activities were less than those of cromolyn sodium and dexamethasone.
These results indicate that flavones containing more hydroxyl radicals have a greater anti-asthmatic effect. The potencies of flavone anti-asthmatic activities are, in order: luteolin ≥ apigenin > baicalein > chrysin > flavone.
[Show abstract][Hide abstract] ABSTRACT: The clinical impact and complications of hepatogenous diabetes (HD) on cirrhosis have not been elucidated. This study aimed to evaluate the relationship of HD with portal hypertension (PHT) and variceal hemorrhage and to assess the prevalence of HD.
From July 2007 to December 2009, 75-g oral glucose tolerance test and insulin resistance (IR) were evaluated for 195 consecutive cirrhotic liver patients (M:F = 164:1, 53.0 ± 10.2 years) who had no history of diabetes mellitus. IR was calculated using the homeostasis model of assessment-insulin resistance (HOMA-IR) formula. Endoscopy for varices, hepatic venous pressure gradient (HVPG), and serologic tests were also conducted.
HD was observed in 55.4 % (108/194) of the patients. Among them, 62.0 % required OGTT for diagnosis because they did not show an abnormal fasting plasma glucose level. The presence of HD showed a significant correlation with high Child-Pugh's score, variceal hemorrhage, and HVPG (p = 0.004, 0.002, and 0.019, respectively). In multivariate analysis, Child-Pugh's score (OR 1.43, 95 % CI 1.005-2.038) and HVPG (OR 1.15, 95 % CI 1.003-2.547) had significant relationships with HD. Patients with recent variceal hemorrhages (within 6 months) exhibited significantly higher glucose levels at 120 min in OGTT compared to patients without hemorrhages (p = 0.042). However, there was no difference in fasting glucose levels. The 120-min glucose level and HOMA-IR score were significantly and linearly correlated with HVPG (r (2) = 0.189, p < 0.001 and r (2) = 0.033, p = 0.011, respectively).
HD and IR have significant relationships with PHT and variceal hemorrhage. Postprandial hyperglycemia in particular had a significant relationship with variceal hemorrhage.
Digestive Diseases and Sciences 08/2013; · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Transcranial magnetic stimulation (TMS) is a noninvasive method of activating or deactivating focal areas of the human brain. Repetitive TMS (rTMS) applied over the temporoparietal cortex has been reported to show therapeutic effects on tinnitus. We compared the effects of 1 Hz rTMS delivered either contralaterally or ipsilaterally to the symptomatic ear in patients with unilateral tinnitus. Forty patients with asymmetric hearing loss and non-pulsatile tinnitus localized to poorer ear of 6 months in duration or greater who were refractory to medication were enrolled in this study. Patients were assigned randomly to one of two treatment groups: with 1 Hz stimulation applied the temporoparietal junction either ipsilaterally (n = 21) or contralaterally (n = 19) to the symptomatic ear. The patients were given 600 pulses per session daily for 5 d. Changes in the tinnitus handicap inventory (THI) and self-rating visual analog scores (VAS) for loudness, awareness and annoyance were analyzed before, immediately after and 1 month after treatment. There was no significant difference in the rate of patients with marked improvement between ipsilateral and contralateral stimulation groups. In addition, there were no significant differences in the amount of decreases in THI scores and VAS between the two groups immediately or 1 month after rTMS. Finally, significant decreases in THI scores and most VAS were observed 1 month after rTMS in both groups compared to pretreatment. Daily treatment with 1 Hz rTMS ipsilaterally and contralaterally to the side of tinnitus both had significant beneficial effects. The laterality of stimulation with 1 Hz rTMS is not the decisive factor in relieving symptoms.
Electromagnetic Biology and Medicine 06/2013; · 0.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The underlying mechanism of atopic dermatitis (AD) exacerbated by Staphylococcus aureus has not been established. However, we demonstrated recently that the majority of S. aureus strains colonized in the skin of Korean AD patients carried genes encoding staphylococcal enterotoxin A (SEA) and/or toxic shock syndrome toxin-1 (TSST-1).
To clarify the role of staphylococcal superantigen, SEA in AD.
With the lesional skin of 9 AD patients and normal looking skin of one healthy adult, we examined first the expression of SEA, staphylococcal enterotoxin B (SEB), and TSST-1 using immunohistochemical analysis. In addition, we investigated the effects of SEA on the expression of inflammation-related adhesion molecules and cytokines in human HaCaT keratinocytes and Human Umbilical Vein Endothelial Cells (HUVECs) by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent assay.
Staphylococcal protein A (SPA) and SEA were detected with increased immunoreactivity in AD patients. However, TSST-1 showed mild-to-moderate immunoreactivity in AD patients, whereas SEB was minimally detected. In the double immunofluorescence investigation, SEA and SPA were well co-localized. SEA induced upregulation of adhesion molecules and elicited inflammatory responses in HaCaT keratinocytes and HUVECs.
This study demonstrates the importance of SEA as an immunoinflammatory triggering factor of AD in Koreans.
Annals of Dermatology 05/2013; 25(2):173-180. · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs).
The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial.
Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values ≤6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003).
Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: SLC26A4 (PDS) mutations are common cause of congenital hearing loss in East Asia. Hearing loss caused by PDS mutations tends to have delayed presentation; thus universal newborn hearing screening (UNHS) can be less effective in these patients. We examined the efficiency of newborn hearing screening test in patients with bi-allelic PDS mutations. METHODS: Forty-three patients with sensorineural hearing loss were recruited. Patients had an enlarged vestibular aqueduct and biallelic PDS mutations. Among them, newborn hearing screening test had been performed on 14. The remaining 29 patients did not undergo newborn hearing screening test. Another 15 patients without a PDS mutation but who had sensorineural hearing loss were also recruited as a comparison group. We reviewed the hearing loss history of the children using medical records and parent interviews. RESULTS: Among 14 patients with PDS mutation, four (28.6%) passed newborn hearing screening test in both ears and six (42.9%) passed in one ear. In contrast, only 2 of 15 (13.3%) children without a PDS mutation passed newborn hearing screening test bilaterally. The age at confirmation of bilateral hearing loss in bilateral "pass" patients with PDS mutation was 31.5±17.9 months, which was significantly delayed compared to the age for bilateral "refer" children (1.75±0.96 months) (p<0.05). CONCLUSION: The UNHS is not an accurate tool for predicting long-term hearing loss in patients with PDS mutations. We recommend that genetic screening be combined with UNHS, particularly in communities with a high prevalence of PDS mutations, to better identify children in need of early habilitation.
International journal of pediatric otorhinolaryngology 03/2013; · 0.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hybrid nanoparticles of LiFePO4 with carbon and lithium phosphates were synthesized through organic–inorganic co-assembly procedure using a triblock copolymer (F108 or P123). We found that the triblock copolymers play a critical role in controlling size of hybrid particle and the degree of crystallinity of the inorganic nanostructures. The hybrid using P-123 had more graphitic carbon which resulted in fast electron mobility. Also, magic angle spinning nuclear magnetic resonance (MAS-NMR) revealed that the crystallinity of the hybrid using P123 is higher than that using F108 which is not measurable in X-ray diffraction. Electrochemical performance of the hybrid using P123 as a cathode material in Li-ion batteries showed superior rate capability at 20 C of charging rate and 2 C of discharging rate without capacity loss, in which discharge capacity was 102 mAh/g.
Journal of Solid State Chemistry 01/2013; 197:53–59. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously found that skin-colonizing Staphylococcus aureus in early childhood atopic dermatitis (AD) originates predominantly from the patient's nose, whereas maternal transmission did not contribute substantially to colonization.
To investigate the transmission route and definitive source of skin-colonizing S aureus in early childhood AD.
A total of 527 children and 32 healthy teachers from 2 kindergartens and 1 elementary school were included in the study. Children were screened for AD and categorized into 3 groups (AD, borderline, and healthy). Samples were collected from 5 to 6 different body sites, including the skin, subungual spaces, and anterior nares. The identity of colonies apparent on mannitol salt agar plates was confirmed by polymerase chain reaction amplification of the nuc gene. The genotypic composition of cultured isolates was examined by pulsed-field gel electrophoresis and analyzed with a dendrogram.
The total colonization rate was higher in the AD group (34.6%) than in the borderline (21.1%) and healthy groups (25.4%). In the AD group, S aureus was more frequently cultured from the subungual areas (30.8%) than the anterior nares (19.2%). To assess self-contamination or recolonization, dendrogram analysis revealed that most isolate pairs (22/23) had the same pulsed-field gel electrophoresis pattern.
As with the anterior nares, the subungual spaces are important reservoir of skin-colonizing S aureus in early childhood AD. The transmission route for self-contamination or recolonization of S aureus appears to be from children's anterior nares to the skin through their own fingers. Child-to-child and/or teacher-to-child transmission in a classroom do not seem to be definite routes of S aureus transmission.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/2012; 109(6):448-53. · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to analyze the oncologic outcomes and the risk factors for recurrence after a tumor-specific mesorectal excision (TSME) of resectable rectal cancer in a single institution.
A total of 782 patients who underwent a TSME for resectable rectal cancer between February 1995 and December 2005 were enrolled retrospectively. Oncologic outcomes included 5-year cancer-specific survival and its affecting factors, as well as risk factors for local and systemic recurrence.
The 5-year cancer-specific survival rate was 77.53% with a mean follow-up period of 61 ± 31 months. The overall local and systemic recurrence rates were 9.2% and 21.1%, respectively. The risk factors for local recurrence were pN stage (P = 0.015), positive distal resection margin, and positive circumferential resection margin (P < 0.001). The risk factors for systemic recurrence were pN stage (P < 0.001) and preoperative carcinoembryonic antigen level (P = 0.005). The prognostic factors for cancer-specific survival were pT stage (P < 0.001), pN stage (P < 0.001), positive distal resection margin (P = 0.005), and positive circumferential resection margin (P = 0.016).
The oncologic outcomes in our institution after a TSME for patients with resectable rectal cancer were similar to those reported in other recent studies, and we established the risk factors that could be crucial for the planning of treatment and follow-up.
Journal of the Korean Society of Coloproctology 04/2012; 28(2):100-7.
[Show abstract][Hide abstract] ABSTRACT: Aim: The purpose of this study was to explore the difference in the pattern of metabolic syndrome (MetS) in urban and rural populations in Korea using data mining techniques. Subjects and Methods: In total, 1,013 adults >30 years of age from urban (184 males and 313 females) and rural districts (211 males and 305 females) were recruited from Gyeongsangnam-do, Korea. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify individuals with MetS. We applied a decision tree analysis to elucidate the differences in the clustering of MetS components between the urban and rural populations. Results: The prevalence of MetS was 33.2% and 35.2% in urban and rural districts, respectively (P = 0.598). The decision-tree approach revealed that the combination of high serum triglycerides (TG) + high systolic blood pressure (SBP), high TG + low HDL-C, and high waist circumference (WC) + high SBP + high fasting plasma glucose (FPG) were strong predictors of MetS in the urban population, whereas the combination of TG + SBP + WC and SBP + WC + FPG showed high positive predictive value for the presence of MetS in the rural population. Conclusions: Although no significant difference was found for the prevalence of MetS between the two populations, the differences in the clustering pattern of MetS components in urban and rural districts in Korea were identified by decision tree analysis. Our findings may serve as a basis to design necessary population-based intervention programs for prevention and progression of MetS and its complications in Korea.
Journal of endocrinological investigation 01/2012; · 1.65 Impact Factor