BACKGROUND: Pyelonephritis is one of the major causes of chronic renal failure in children, and the transforming growth factor-beta1 (TGF-beta1) is a molecule with pivotal roles in fibrogenesis. This study was performed to investigate the alteration and clinical implications of urinary TGF-beta1/creatinine ratio in children with acute pyelonephritis. METHODS: Urine was collected from 67 normal children and 25 children with acute pyelonephritis. After routine urinalysis, urine TGF-beta1 was quantitated by ELISA method and creatinine was measured by alkaline picrate method. Urinary TGF-beta1/ creatinine ratios in children with pyelonephritis were compared with those of age-matched controls, and sequential changes of the ratios in pyelonephritic children were traced after antibiotic treatment. Correlation of urinary TGF-beta1/creatinine ratio with the degree of pyuria and renal scar was analyzed each. RESULTS: Neonates showed higher urinary TGF-beta1/creatinine ratios than older children. The ratio increased in acute pyelonephritis and gradually returned to the control level two days after antibiotic treatment. Urinary TGF-beta1/creatinine ratio in acute pyelonephritis was not correlated with the degree of pyuria and renal scar. CONCLUSION: The age should be considered in evaluation of urinary TGF-beta1/creatinine ratio in children. The ratio increases in acute pyelonephritis, and is independent of the degree of pyuria or renal scarring.
Child ; Cicatrix ; Creatinine ; Enzyme-Linked Immunosorbent Assay ; Humans ; Infant, Newborn ; Kidney Failure, Chronic ; Pyelonephritis* ; Pyuria ; Transforming Growth Factor beta1 ; Urinalysis

HPV E2 protein is known to act as a negative regulator of transcription and the disruption of E2 open reading frame by HPV integration can release suppression of E6 and E7 mRNA expression, resulting in uncontrolled cellular growth and malignant transformation by inactivating tumor suppressor gene products (p53, pRb). YY1 mutation of HPV URR has been suggested as one of indicator that explains development of cervical neoplasia by episomal type of HPV. To extend this hypothesis, we examined whether mutation(s) in specific sites of HPV URR is functionally related to the invasiveness of cervical neoplasia and the physical status of HPV DNA. The URR sequences were obtained by PCR amplification of HPV-16 genome from CIN and invasive cancer patients, cloned into pUC18 for sequencing, and into pBLCAT8+ for functional CAT assay. Our previous data classified HPV-infected patients into three groups: 3 cancer cases carrying episomal HPV DNA; 12 cancer cases carrying integrated HPV DNA; 12 CIN cases carrying episomal HPV DNA. The specific variants in HPV-16 URR were found in Korean women: GA transition at nt 7520 (100%, 27/27), AC transition at nt 7729 (70%; 19/27), and GA transition at nt 7841 (78%; 21/27). Selective mutations were observed at the YY1-binding sites of HPV-16 URR in the 3 patients with invasive cervical cancer, who having the episomal forms of HPV-16 DNA: AC transition at nt 7484 and GA transition at nt 7488 (YY1-binding site 2; from 7481 to 7489). Additionally, CT transition at nt 7785 (YY1-binding site 3; from 7781 to 7790) was found from 2 of 3 patients. No YY1 site mutations were detected in the 12 CIN patients and in the HPV-integrated invasive cancer patients. To determine whether these mutations have effect on the expression of HPV E6/E7 genes driven by URR, the transient transfection assay was employed using URR-CAT reporter plasmid. The relative activities of three URR mutants from episomal HPV-16 DNA of cervical cancers were 2- to 4-fold higher than that of HPV-16 URR prototype. In contrast, the URRs from integrated HPV-16 DNA in cervical cancer and from episomal HPV-16 DNA in CIN, where no mutation of the YY1-binding site was detected, showed similar levels of promoter activity to that of URR prototype.Our results support the hypothesis that the mutation at YY1 binding site is functionally related to the development of cervical neoplasia caused by episomal HPV-16 DNA in Korean cervical cancer patient. Thus, mutation in YY1 site of episomal HPV-16 URR may play a role of HPV integration in the progression of cervical cancer.
Animals ; Binding Sites ; Cats ; Clone Cells ; DNA* ; Female ; Genes, Tumor Suppressor ; Genome ; Human papillomavirus 16* ; Humans ; Open Reading Frames ; Plasmids ; Polymerase Chain Reaction ; RNA, Messenger ; Transfection ; Uterine Cervical Neoplasms

PURPOSE: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-beta1. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-beta. MATERIALS AND METHODS: Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-beta1 in renal tissue-conditioned media was measured by ELISA. RESULTS: Masson-trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson-trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-beta1 concentration among the groups. CONCLUSION: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-beta expression.
Animals ; Connective Tissue Growth Factor ; Dipyridamole ; Drinking Water ; Enzyme-Linked Immunosorbent Assay ; Fibronectins ; Fibrosis* ; Ligation ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Ureter* ; Ureteral Obstruction*

PURPOSE: We report on cases of anatomical popliteal artery entrapment syndrome (PAES) caused by an aberrant plantaris muscle and highlight the involvement of this muscle in PAES. MATERIALS AND METHODS: Seven symptomatic PAES legs in six patients treated at The Division of Vascular Surgery, Asan Medical Center, Seoul, Korea, between 1995 and 2011 were included in this study. We retrospectively analyzed patient records, magnetic resonance imaging (MRI) and/or computed tomography (CT) scans of the knee joint, Doppler pressure studies, CT angiographies, and conventional femoral arteriographies. RESULTS: Five males and one female patient with a median age of 32 (18-53) years old were enrolled in the study. All patients complained of intermittent claudication of the affected leg. All aberrant plantaris muscles were higher and more medially located than normal plantaris muscles, causing occlusion of the popliteal artery upon forced plantar flexion of the ankle. For arterial lesions, five occlusions of the popliteal artery and two patent popliteal arteries with positive provocation were noted. As for treatment, myotomy of the aberrant plantaris muscle was done for two non-occlusive PAES legs. For occlusive PAES legs, one thrombectomy, one saphenous vein graft interposition of the popliteal artery followed by myotomy, and two below-knee femoro-popliteal bypasses were performed. The median follow-up period was 88 (7-148) months. CONCLUSION: An aberrant plantaris muscle can cause anatomical PAES. Classification or diagnosis of PAES should be based on axial studies using CT scans or MRI using various reconstruction methods. Treatment, including myotomy of the plantaris muscle, should be individualized.
Angiography ; Ankle ; Chungcheongnam-do ; Classification ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Intermittent Claudication ; Knee Joint ; Korea ; Leg ; Magnetic Resonance Imaging ; Male ; Muscle, Skeletal* ; Muscles ; Popliteal Artery* ; Retrospective Studies ; Saphenous Vein ; Seoul ; Thrombectomy ; Tomography, X-Ray Computed ; Transplants

BACKGROUNDS/AIMS: Standard liver volume (SLV) is an important parameter that has been used as a reference value to estimate the graft matching in living donor liver transplantation (LDLT). This study aimed to determine a reliable SLV formula for Korean adult patients as compared with the 15 SLV formulae from other studies and further estimate SLV formula by gender and body mass index (BMI). METHODS: Computed tomography liver volumetry was performed in 1,000 living donors for LDLT and regression formulae for SLV was calculated. Individual donor data were applied to the 15 previously published SLV formulae, as compared with the SLV formula derived in this study. Analysis for confounding variables of BMI and gender was also performed. RESULTS: Two formulae, "SLV (ml)=908.204xBSA-464.728" with DuBois body surface area (BSA) formula and "SLV (ml)=893.485xBSA-439.169" with Monsteller BSA formula, were derived by using the profiles of the 1,000 living donors included in the study. Comparison with other 15 other formulae, all except for Chouker formula showed the mean volume percentage errors of 4.8-5.4%. The gender showed no significant effect on total liver volume (TLV), but there was a significant increase in TLV as BMI increased. CONCLUSIONS: Our study suggested that most SLV formulae showed a crudely applicable range of SLV estimation for Korean adults. Considering the volume error in estimating SLV, further SLV studies with larger population from multiple centers should be performed to enhance its predictability. Our results suggested that classifying SLV formulae by BMI and gender is unnecessary.
Adult* ; Body Mass Index ; Body Surface Area ; Confounding Factors (Epidemiology)* ; Humans ; Liver Transplantation ; Liver* ; Living Donors ; Reference Values ; Tissue Donors ; Transplants

Background/Aims: Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. Methods: Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). Results: Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). Conclusions HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.

While the ability to develop nanomaterials and incorporate them into products is advancing rapidly worldwide, understanding of the potential health safety effects of nanomaterials has proceeded at a much slower pace. Since 2008, Korea Food and Drug Administration (KFDA) started an investigation to prepare "Strategic Action Plan" to evaluate safety and nano risk management associated with foods, drugs, medical devices and cosmetics using nano-scale materials. Although there are some studies related to potential risk of nanomaterials, physical-chemical characterization of nanomaterials is not clear yet and these do not offer enough information due to their limitations. Their uncertainties make it impossible to determine whether nanomaterials are actually hazardous to human. According to the above mention, we have some problems to conduct the human exposure risk assessment currently. On the other hand, uncertainty about safety may lead to polarized public debate and to businesses unwillingness for further nanotechnology investigation. Therefore, the criteria and methods to assess possible adverse effects of nanomaterials have been vigorously taken into consideration by many international organizations: the World Health Organization, the Organization for Economic and Commercial Development and the European Commission. The object of this study was to develop risk assessment principles for safety management of future nanoproducts and also to identify areas of research to strengthen risk assessment for nanomaterials. The research roadmaps which were proposed in this study will be helpful to fill up the current gaps in knowledge relevant nano risk assessment.
Commerce ; Cosmetics ; Hand ; Humans ; Korea ; Nanostructures ; Nanotechnology ; Risk Assessment ; Risk Management ; Safety Management ; Uncertainty ; United States Food and Drug Administration ; World Health Organization

Background/Aims: Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. Methods: The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. Results: The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. Conclusions The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

BACKGROUND/AIMS: In addition to the globally endorsed Barcelona Clinic Liver Cancer (BCLC) staging system, other algorithms or staging systems have been developed, including the Hong Kong Liver Cancer (HKLC) staging system. This study aimed to validate the HKLC staging system relative to the BCLC staging system for predicting survival for hepatocellular carcinoma (HCC) patients in Korea. METHODS: From 2004 to 2013, 2,571 patients newly diagnosed with HCC were consecutively enrolled at three Korea University medical centers. RESULTS: Both staging systems differentiated survival well (p < 0.001). However, 1-year and 3-year survival were predicted better using the HKLC system than the BCLC system (area under the receiver operating characteristic curve: 0.869 vs 0.856 for 1 year, p=0.002; 0.841 vs 0.827 for 3 years, p=0.010). In hypothetical survival curves, the HKLC system exhibited better median overall survival than the BCLC system (33.1 months vs 19.2 months). In evaluations of prognosis according to either BCLC or HKLC treatment guidelines, risk of death was reduced in the group following only HKLC guidelines compared with the group following only BCLC guidelines (hazard ratio, 0.601; 95% confidence interval, 0.443 to 0.816; p=0.001). CONCLUSIONS: Although both staging systems predicted and discriminated HCC prognoses well, the HKLC system showed more encouraging survival benefits than the BCLC system.
Academic Medical Centers ; Carcinoma, Hepatocellular ; Hong Kong ; Humans ; Korea ; Liver Neoplasms ; Liver ; Neoplasm Staging ; Prognosis ; ROC Curve