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1.
Phys Rev Lett ; 131(1): 015102, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37478441

ABSTRACT

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

2.
J Appl Microbiol ; 134(7)2023 Jul 04.
Article in English | MEDLINE | ID: mdl-37385824

ABSTRACT

AIMS: Streptococcus parauberis is responsible for the development of streptococcosis in marine fish. The aim of the current study was to determine the antimicrobial susceptibility of aquatic Strep. parauberis strains, thus establishing laboratory-specific epidemiological cut-off (COWT) values to distinguish wild-type (WT) and nonwild-type (NWT) strains. METHODS AND RESULTS: Using 220 Strep. parauberis isolates obtained from diseased Paralichthys olivaceus, Platichthys stellatus, and Sebastes schlegelii over 6 years from seven different locations in Korea, we established COWT values for eight common antimicrobial agents using the standard broth microdilution method. The COWT values calculated using MIC distribution with the NRI and ECOFFinder methods were the same or within one dilution step for the eight antimicrobials tested. Nine NWT isolates with decreased susceptibility to at least two antimicrobials and one of these isolates exhibited decreased susceptibility to six antimicrobial agents were identified using COWT values based on NRI. CONCLUSIONS: Interpretive criteria for Strep. parauberis have not yet been established, and the findings of this study provide putative COWT values for eight antimicrobial agents frequently used in aquaculture in Korea.


Subject(s)
Fish Diseases , Flounder , Streptococcal Infections , Animals , Streptococcus/genetics , Anti-Bacterial Agents , Streptococcal Infections/veterinary , Microbial Sensitivity Tests
3.
Antibiotics (Basel) ; 11(3)2022 Mar 05.
Article in English | MEDLINE | ID: mdl-35326806

ABSTRACT

The emergence of antimicrobial-resistant bacteria is an enormous challenge to public health. Aeromonas hydrophila and Aeromonas veronii are opportunistic pathogens in fish. They exert tremendous adverse effects on aquaculture production, owing to their acquired antibiotic resistance. A few Clinical and Laboratory Standards Institute (CLSI) epidemiological cut-off values (ECVs) against Aeromonas spp. are available. We evaluated antimicrobial susceptibility by establishing 8 ECVs using two analytical methods, normalized resistance interpretation and ECOFFinder. We detected antimicrobial resistance genes in two motile Aeromonas spp. isolated from aquatic animals. Results showed that 89.2% of A. hydrophila and 75.8% of A. veronii isolates were non-wild types according to the oxytetracycline ECVCLSI and ECVNRI, respectively. The antimicrobial resistance genes included tetA, tetB, tetD, tetE, cat, floR, qnrA, qnrB, qnrS, strA-strB, and aac(6')-1b. The most common tet gene in Aeromonas spp. isolates was tetE, followed by tetA. Some strains carried more than one tet gene, with tetA-tetD and tetA-tetE found in A. hydrophila; however, tetB was not detected in any of the strains. Furthermore, 18.6% of A. hydrophila and 24.2% of A. veronii isolates showed presumptive multidrug-resistant phenotypes. The emergence of multidrug resistance among aquatic aeromonads suggests the spread of drug resistance and difficult to treat bacterial infections.

4.
J Interpers Violence ; 37(23-24): NP22428-NP22452, 2022 12.
Article in English | MEDLINE | ID: mdl-35184579

ABSTRACT

Adverse effects of childhood maltreatment experience and adolescent depression symptoms are theorized to be more profound for adolescents who have suffered multiple maltreatments (polyvictimization). New theoretical insights into the study of polyvictimization suggest that it must be studied using a multiplicative logic, particularly when maltreatment is characterized by invasive exploitation. This study, for the first time, examined the concept of invasive exploitation in the context of polyvictimization and its association with adolescent depression symptoms. The study used a random, three stage probability proportional to size (PPS) cluster sample of 565 mother-adolescent dyads in Kathmandu, Nepal, and also examined the protective effects of maternal empathy. We hypothesized that (a) singly, the empirical categories of maltreatment (neglect, physical abuse, and child sexual abuse) would associate positively with adolescent depressive symptoms and (b) main effects held constant, the interaction effects of a child sexual abuse X neglect and a child sexual abuse X physical abuse would be positive. Regression with clustering corrections found that neglect (B = 3.17, p < .01) and sexual abuse (B = 3.48, p < .05) positively associated with adolescent depression symptoms. Results support the multiplicative invasive exploitation polyvictimization hypothesis (child sexual abuse X neglect interaction; B = 6.14, p < .05). The positive neglect X sexual abuse interaction is consistent with the theory that sexual abuse is distinct as invasive exploitation, and demonstrates that the multiplicative hypothesis can be fruitfully applied to the study of polyvictimization. Interventions targeting polyvictims with experience of invasive exploitation and studies aiming to provide deeper insights into sexual abuse as invasive exploitation are needed.


Subject(s)
Child Abuse, Sexual , Child Abuse , Child , Female , Adolescent , Humans , Depression/epidemiology , Nepal , Physical Abuse
5.
Article in English | MEDLINE | ID: mdl-34673250

ABSTRACT

Scuticociliatosis, caused by Miamiensis avidus, is a severe parasitic disease affecting marine organisms, particularly Paralichthys olivaceus. The aim of this study was to assess the antiparasitic potential of ethanolic extracts of Carpesii Fructus (EECF), the dried fruit of Carpesium abrotanoides L., which is used in traditional Chinese medicine, in vitro. We found that 50%, 70%, and 100% EECF induced morphological changes in M. avidus, including reduced motility, cell shrinkage, and lysis. Nearly 100% cell lysis was observed in M. avidus after 2 h of treating with 100% EECF. After 24 h, the survival rates of M. avidus treated with 100%, 70%, and 50% EECF were 10%, 20%, and 30%, respectively. Additionally, the mRNA levels of immune response-related (IL-1ß, IL-8, TNF-α, and CD8-α) and biotransformation-related (CYP1A, CYP1B, CYP3A4, and UGT2B19) genes increased with 70% and 100% EECF treatment and decreased with 50% EECF treatment following pretreatment with concanavalin A. The viability of hirame natural embryo (HINAE) cells was reduced by 50%, 70%, and 100% EECF (100 mg/L) and was between 67 and 80%. The IC50 values of 50%, 70%, 90%, and 100% EECF in HINAE cells were 102.3, 42.93, 39.15, and 38.39 mg/L, respectively. These results indicated that 50% EECF was less toxic to HINAE cells than 70% or 100% EECF, while still exhibiting antiparasitic activity against M. avidus. Therefore, we demonstrated the role of EECF as a natural antiparasitic agent against M. avidus. Our findings suggest that Carpesii Fructus has potential use as an antiparasitic agent in the aquaculture industry.


Subject(s)
Antiparasitic Agents/pharmacology , Asteraceae/metabolism , Fish Diseases , Flounder/parasitology , Parasitic Diseases, Animal/drug therapy , Plant Extracts/pharmacology , Animals , Cell Line , Fish Diseases/drug therapy , Fish Diseases/parasitology , Immunity/drug effects
6.
Proteomics Clin Appl ; 12(5): e1700125, 2018 09.
Article in English | MEDLINE | ID: mdl-29476606

ABSTRACT

PURPOSE: Secretory carcinoma (SC) of the breast is defined as an indolent tumor but is still categorized into a basal-like triple-negative breast cancer (BL-TNBC) subgroup that generally shows aggressive behavior according to the current classification. Despite the unique clinical behavior of SC, molecular characteristics that reflect biological behaviors of SC remain largely unknown. EXPERIMENTAL DESIGN: A combinatorial approach of whole-exome sequencing and mass spectrometry-based in-depth quantitative proteomics to determine the entire molecular landscape of SC using three SC formalin-fixed paraffin-embedded (FFPE) tissues is employed. RESULTS: Exome sequencing and proteomic analysis of SC identified 419 unique somatic mutations and 721 differentially expressed proteins as compared with triple-negative breast cancer (TNBC), respectively. Several pathways related to cancer metabolism were significantly upregulated in the SC group. Comparative analyses with multiple datasets revealed that SC shares genomic mutations and biological pathways more closely related to hormone receptor-positive breast cancer than BL-TNBC. CONCLUSION AND CLINICAL RELEVANCE: These multi-omic analyses provide evidence that SC harbors substantially different molecular genomic and proteomic landscapes compared with BL-TNBC. These results provide an entire spectrum of in-depth molecular landscapes to support the hypothesis that SC is distinct from BL-TNBC.


Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Proteomics , Triple Negative Breast Neoplasms/genetics , Breast Neoplasms/classification , Breast Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Mutation , Triple Negative Breast Neoplasms/classification , Triple Negative Breast Neoplasms/pathology , Exome Sequencing
7.
Acta Biochim Biophys Sin (Shanghai) ; 47(11): 938-45, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26376742

ABSTRACT

The TetR family transcriptional regulator AefR contributes to the regulation of the quorum-sensing system. However, the role of AefR in the regulatory network of the phytopathogen Pseudomonas syringae pathovars is not known. In this study, the phenotype of a P. syringae pv. tabaci 11528 aefR deletion mutant strain was examined. The aefR gene expression and AefR DNA-binding affinity were examined by quantitative real-time polymerase chain reaction and electrophoretic mobility shift assay, respectively. AefR was found to control quorum-sensing genes as well as the efflux genes mexE, mexF, and oprN via an indirect mechanism. AefR binds to its own operator site as well as to the palindromic sequence between positions -28 and -2 corresponding to the transcription start site of aefR, as determined by dye primer sequencing. These results suggest that P. syringae AefR modulates quorum sensing and efflux as well as its own expression, which can be exploited by strategies developed to manage this plant parasite.


Subject(s)
Bacterial Proteins/metabolism , Pseudomonas syringae/genetics , Pseudomonas syringae/metabolism , Quorum Sensing , Regulatory Elements, Transcriptional , Mutation , Real-Time Polymerase Chain Reaction
8.
Child Abuse Negl ; 41: 170-81, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25455214

ABSTRACT

Drawing on previous research on intimate partner violence, child maltreatment, and informal social control, we hypothesized relationships between child abuse severity and (1) protective informal social control of intimate partner violence (ISC_IPV) by neighbors, (2) intimate terrorism, (3) family order, and (4) the power of mothers in intimate relationships. In what we believe may be a first study of physical child abuse by parents in Nepal, we used a three stage cluster approach to draw a random sample of 300 families in Kathmandu. Random effects regression models were used to test the study hypotheses. The analyses found support for hypotheses one and two, but with an important caveat. Although observed (actual) protective ISC_IPV had the hypothesized negative association with child abuse severity, in one of our models perceived protective ISC_IPV was positively associated with child abuse severity. The models clarify that the overall direction of protective ISC_IPV appears to be negative (protective), but the positive finding is important to consider for both research and practice. A significant relationship between family order and child abuse severity was found, but the direction was negative rather than positive as in hypothesis three. Implications for neighborhood research and typological research on IPV and child maltreatment are discussed.


Subject(s)
Child Abuse/prevention & control , Intimate Partner Violence/statistics & numerical data , Social Control, Informal , Adult , Child , Family , Female , Humans , Interpersonal Relations , Male , Mothers/psychology , Nepal/epidemiology , Power, Psychological , Regression Analysis , Residence Characteristics
9.
Colloids Surf B Biointerfaces ; 122: 752-759, 2014 Oct 01.
Article in English | MEDLINE | ID: mdl-25194592

ABSTRACT

The development of iron oxide nanoparticles (IONPs) with enhanced r2 relaxivity is important for achieving greater sensitivity in in vivo magnetic resonance (MR) imaging. In this study, it was considered that polyethyleneimine (PEI) could play a role in varying the particle and cluster sizes in IONP synthesis, leading to different r2 relaxivities. To demonstrate this, superparamagnetic IONPs were synthesised in the presence of NH4OH and PEI using a co-precipitation method. PEI acted as an active stabiliser during IONP synthesis, and therefore the particle size, hydrodynamic cluster size, coating layer thickness, saturation magnetisation, and r2 relaxivity were all strongly influenced by the PEI concentration. Monodispersed IONPs with a mean hydrodynamic cluster size of 14.4nm were synthesised at a PEI concentration of 0.05wt% and in this case, the r2 relaxivity was increased up to 227.6mM(-1)s(-1). This confirmed the viability of PEI-mediated synthesis as a means of controlling the particle/cluster size and enhancing the r2 relaxivity. The PEI-IONPs exhibited no significant cytotoxicity up to 132ppm. Rapid and strong uptake of PEI-IONPs was detected in rat liver by in vivo MR imaging. The superparamagnetic PEI-IONPs prepared in this study are considered to be sufficiently sensitive for use as MR imaging contrast agents, which can be used as parent particles for further functional modification.


Subject(s)
Ferric Compounds/chemistry , Magnetic Resonance Imaging/methods , Nanoparticles/chemistry , Polyethyleneimine/chemistry , Animals , Ferric Compounds/chemical synthesis , Male , Particle Size , Rats , Rats, Sprague-Dawley
10.
J Diabetes Investig ; 5(3): 297-304, 2014 May 04.
Article in English | MEDLINE | ID: mdl-24843778

ABSTRACT

AIMS/INTRODUCTION: Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have evaluated the association between insulin and colorectal adenoma. We investigated the relationship between fasting serum insulin levels or homeostasis model assessment of insulin resistance (HOMA-IR) and colorectal adenoma. MATERIALS AND METHODS: We retrospectively enrolled 15,427 participants who underwent both fasting serum insulin measurement and colonoscopy for a routine health examination at Asan Medical Center from January 2007 to December 2008. Participants with a history of any cancer, previous colectomy or polypectomy, those taking antidiabetic medications, and inflammatory bowel disease, non-specific colitis, non-adenomatous polyps only or CRC on colonoscopic findings were excluded. Finally, 3,606 participants with histologically confirmed colorectal adenoma and 6,019 controls with no abnormal findings on colonoscopy were included. Participants were categorized into quartiles (Q) based on fasting serum insulin levels and HOMA-IR. RESULTS: Fasting serum insulin and HOMA-IR were significantly higher in participants with colorectal adenomas compared with controls. Multivariate regression analysis adjusting for age, sex, smoking habits, drinking habits and family history of CRC showed that participants with higher quartiles of fasting serum insulin levels (odd ratio [OR] 1.17 for 2nd Q, 1.19 for 3rd Q, and 1.42 for 4th Q, P < 0.05) or HOMA-IR (OR 1.18 for 2nd Q and 1.45 for 4th Q, P < 0.05) showed significantly increased ORs of colorectal adenoma compared with the lowest quartiles. CONCLUSIONS: These findings showed that increased serum insulin levels and insulin resistance were significantly associated with the presence of colorectal adenoma.

11.
Helicobacter ; 18(4): 299-308, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23521610

ABSTRACT

BACKGROUND: Studies on seroconversion and its reversion rate in Korean adults with Helicobacter pylori infection are very rare. The purpose of this study was to evaluate the overall seroprevalence, seroconversion rate, and seroreversion rate of H. pylori infection in an adult population. MATERIALS AND METHODS: We performed this retrospective cohort study on healthy adults who had visited our health screening center at Asan Medical Center more than twice between January 2000 and December 2010. We reviewed the anti- H. pylori Ab IgG profiles of the enrolled people and their family members and the results of esophagogastroduodenoscopies and a self-reported questionnaire. RESULTS: A total of 67,212 people were enrolled in this study. The mean follow-up duration was 4.6 years, and each participant visited the center for a mean of 3.8 visits. The overall proportions of participants demonstrating persistent seropositivity, persistent seronegativity, seroconversion, and seroreversion were 53.1%, 32.5%, 4.3%, and 10.1%, respectively. The annual seroconversion rate was 2.79%. The annual crude and spontaneous seroreversion rates of the entire study population were 3.64% and 2.42%, respectively. According to multivariate logistic regression, old age (HR = 1.015), smoking (HR = 1.216), alcohol consumption more than four times per week (HR = 1.263), marriage (HR = 2.735), and living with H. pylori-infected family members (HR = 1.525) were identified as statistically significant risk factors associated with seroconversion. CONCLUSION: The annual seroconversion rate was 2.79% in our study population. Marriage and living with H. pylori-infected family members were important risk factors affecting seroconversion in our adult population.


Subject(s)
Antibodies, Bacterial/blood , Helicobacter Infections/epidemiology , Helicobacter pylori/immunology , Adult , Aged , Cohort Studies , Female , Humans , Immunoglobulin G/blood , Incidence , Korea/epidemiology , Male , Middle Aged , Retrospective Studies , Seroepidemiologic Studies , Surveys and Questionnaires
12.
Dig Dis Sci ; 56(6): 1818-27, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21222160

ABSTRACT

BACKGROUND AND AIMS: Researchers have not clearly described the clinical and pathogenetic features of hypoganglionosis and adult-onset Hirschsprung's disease, which cause pseudo-obstruction or intractable constipation. We conducted this study to explore these features of hypoganglionosis and adult-onset Hirschsprung's disease in Korean patients. METHODS: We enrolled 24 patients pathologically confirmed as having hypoganglionosis and 11 as having adult-onset Hirschsprung's disease. We recruited 26 subjects who had undergone operation for nonobstructive colon cancer and 45 healthy volunteers as controls. We described their clinical features, investigated ganglion cells and interstitial cells of Cajal (ICC), and analyzed RET, EDNRB, EDN3, and SOX10 genes. RESULTS: We classified hypoganglionosis patients into two groups: type I (focal type, n = 13), with focally narrowed transition zone (TZ); and type II (diffuse type, n = 11), without transition zone. Hypoganglionosis patients had significantly fewer ganglion cells than the controls, and those cells were scarcer in the transition zone than in the proximal dilated area (P < 0.05). The ICC numbers in both diseases were significantly lower than in controls; however, they were similar between transition zone and the proximal dilated area in hypoganglionosis. In adult-onset Hirschsprung's disease, two significant intronic RET polymorphic variants, IVS14-24G>A and IVS19+47T>C, were significantly associated with adult-onset Hirschsprung's disease (P = 0.0122 and 0.0295, respectively), but not with hypoganglionosis. CONCLUSIONS: Hypoganglionosis and adult-onset Hirschsprung's disease have different pathophysiologic characteristics, although their clinical presentations are similar. We suggest that there are two subgroups of hypoganglionosis: those with or without a focally narrowed transition zone with a profoundly diminished number of ganglion cells.


Subject(s)
Colon/innervation , Ganglia, Autonomic/pathology , Hirschsprung Disease/classification , Hirschsprung Disease/pathology , Adolescent , Adult , Aged , Child , Female , Gene Expression Regulation , Hirschsprung Disease/genetics , Humans , Male , Middle Aged , Mutation , Myenteric Plexus/cytology , Polymorphism, Genetic , Proto-Oncogene Proteins c-ret/genetics , Proto-Oncogene Proteins c-ret/metabolism , Young Adult
13.
J Gastroenterol Hepatol ; 25(11): 1785-94, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21039842

ABSTRACT

BACKGROUND AND AIM: A Western-style diet (WD) is known to play an important role in inflammatory bowel disease and colon carcinogenesis. The purpose of this study was to understand the role of macrophages in WD-induced colitis associated with carcinogenesis. METHODS: Male BALB/c mice were fed a WD or a control diet (CD) for 4 weeks and exposed to azoxymethane (AOM) followed by 2% dextran sulfate sodium (DSS) for 7 days. RESULTS: The WD increased susceptibility to DSS-induced inflammation and accelerated the infiltration of macrophages. The incidence and multiplicity of colon tumors were higher in mice fed the WD than in those fed the CD (P < 0.05). Levels of prostaglandin-endoperoxide synthase (PTGS) 2 and prostaglandin (PG) E(2) in the colon were higher after treatment with AOM and DSS in mice fed the WD than in those fed the CD. In addition, WD consumption increased the DNA binding activity of nuclear factor-kappaB and the serum concentration of tumor necrosis factor (TNF)-α. Mice fed the WD had higher numbers of F4/80-positive cells surrounding cancer cells compared with mice fed the CD. These cells expressed PTGS2, TNF-α and ß-catenin, which are up-regulated by the WD. We also found that the WD increased unphosphorylated ß-catenin accumulation in the cytoplasm and nucleus of colon cancer cells. CONCLUSIONS: A WD increases the susceptibility to DSS-induced inflammation and accelerates the infiltration of macrophages. In turn, this resulted in the development and progression of colon cancer.


Subject(s)
Cell Transformation, Neoplastic/immunology , Colitis/complications , Colitis/immunology , Colonic Neoplasms/immunology , Diet/adverse effects , Macrophages/immunology , Signal Transduction/immunology , Animals , Azoxymethane , Colitis/chemically induced , Colonic Neoplasms/chemically induced , Dextran Sulfate , Dinoprostone/metabolism , Disease Susceptibility , Hydroxyprostaglandin Dehydrogenases/metabolism , Macrophages/metabolism , Male , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , RNA, Messenger/metabolism , Statistics, Nonparametric , Tumor Necrosis Factor-alpha/metabolism , beta Catenin/metabolism
14.
Korean J Physiol Pharmacol ; 14(2): 77-81, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20473378

ABSTRACT

Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR alpha), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.

15.
Life Sci ; 86(19-20): 716-21, 2010 May 08.
Article in English | MEDLINE | ID: mdl-20226795

ABSTRACT

AIMS: Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARalpha) agonist that has been widely used to treat dyslipidemia. Previous studies have suggested that fenofibrate plays a role in cell proliferation and the development of hepatocarcinoma, but the underlying mechanism has not been fully characterized. In this report, we investigated whether fenofibrate treatment affected on the machinery of cell cycle checkpoint using nocodazole-induced cell cycle arrest. MAIN METHODS: The human normal liver cell line, CCL13 cells were treated with nocodazole and fenofibrate. Flow cytometry was performed for cell cycle analysis, and checkpoint kinase 2 (Chk2) and phosphatase Wip1 were analyzed by Western blot. KEY FINDINGS: Fenofibrate treatment overrode nocodazole-induced G2/M cell cycle arrest in a PPARalpha-independent manner. Mechanistically, fenofibrate treatment inhibited phosphorylation of checkpoint kinase Chk2 induced by nocodazole, and increased the expression of Wip1, a negative regulator of Chk2, suggesting that fenofibrate suppressed the nocodazole-induced G2/M cell cycle checkpoint through Wip1-mediated inhibition of Chk2 activation. SIGNIFICANCE: These results reveal a novel role of fenofibrate in cell cycle checkpoint control and provide a possible mechanistic explanation for how fenofibrate promotes cell proliferation and carcinogenesis.


Subject(s)
Cell Proliferation/drug effects , Fenofibrate/pharmacology , Hypolipidemic Agents/pharmacology , Phosphoprotein Phosphatases/genetics , Protein Serine-Threonine Kinases/antagonists & inhibitors , Blotting, Western , Cell Division/drug effects , Cell Line , Checkpoint Kinase 2 , Flow Cytometry , G2 Phase/drug effects , Humans , Nocodazole/pharmacology , PPAR alpha/agonists , Phosphoprotein Phosphatases/metabolism , Phosphorylation/drug effects , Protein Phosphatase 2C
16.
Gut Liver ; 4(4): 488-97, 2010 12.
Article in English | MEDLINE | ID: mdl-21253297

ABSTRACT

BACKGROUND/AIMS: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages. METHODS: WE UTILIZED TWO MURINE COLON CANCER MODELS: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe. RESULTS: Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa. CONCLUSIONS: NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease.

17.
J Clin Gastroenterol ; 43(8): 737-42, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19262405

ABSTRACT

BACKGROUND: Double balloon endoscopy (DBE) is a new endoscopic method with the capability for complete observation of whole small bowel. This study evaluated the feasibility and usefulness of DBE for the diagnosis and therapy of small bowel diseases in patients with distorted intestinal anatomy by previous surgeries. PATIENTS AND METHODS: From January 2005 to August 2007, 15 patients with Roux-en-Y anastomosis underwent DBE in Asan Medical Center. Eight were men and the median age was 57 years (range, 40 to 68 y). Indications of DBE were suspected small bowel bleeding, chronic diarrhea, and recurrent acute pancreatitis. The main outcome measurements included completeness of the observation of afferent loop and DBE findings. RESULTS: Because 1 patient underwent DBE twice separately owing to recurrent bleeding, a total of 16 cases were analyzed. The observation of afferent loop was complete in 13 (81%) of 16 cases. The overall diagnostic yield of DBE was 69% (11/16). Out of 11 cases in which DBE detected abnormalities, 6 (55%) showed definite lesions and 5 (45%) probable lesions. Of the 11 cases in which abnormalities were found, 7 (64%) showed lesions in afferent loop. Of the 6 cases in which definite lesions were found, 4 (67%) showed lesions in afferent loop. Therapeutic endoscopic procedures were performed in 4 cases, which include argon plasma coagulation, foreign body removal, and endoscopic nasobiliary drainage. CONCLUSIONS: DBE in patients with distorted intestinal anatomy such as Roux-en-Y anastomosis is a useful tool for the management of small bowel lesions, especially those in the afferent loop.


Subject(s)
Catheterization , Endoscopes, Gastrointestinal , Endoscopy, Gastrointestinal , Intestinal Diseases/surgery , Intestine, Small/surgery , Adult , Aged , Anastomosis, Roux-en-Y/adverse effects , Equipment Design , Female , Humans , Intestinal Diseases/diagnosis , Intestinal Diseases/therapy , Intestine, Small/pathology , Male , Middle Aged
18.
Korean J Gastroenterol ; 53(2): 76-83, 2009 Feb.
Article in Korean | MEDLINE | ID: mdl-19237832

ABSTRACT

BACKGROUND/AIMS: The aim of this study was to evaluate the changes in prevalence and the related factors of Helicobacter pylori (H. pylori) infection in Korean health check-up subjects during the period of 8 years. METHODS: Among 89,231 subjects who visited the Health Promotion Centers of Severance hospital or Chung-Ang University hospital from Jan. 1998 through Dec. 2005, a total of 10,553 subjects who received esophagogastroduodenoscopy (EGD) and H. pylori test were enrolled. H. pylori infection was assessed by histologic examination. Changes of the prevalence of H. pylori infection during 8 years, and infection-related factors such as demographic characteristics, body mass index, ABO blood types, endoscopic findings (presence of peptic ulcer diseases), educational level, economic status, smoking habits, and alcohol intake in year 2005 were analyzed. RESULTS: The mean age of 10,553 subjects (7,329 men, 3,224 women) was 49.7+/-10.4 years (range from 17 to 92 years). The prevalence of H. pylori infection at the first, second, third, fourth, fifth, sixth, seventh, and eighth year were 64.7%, 58.1%, 54.2%, 50.4%, 48.9%, 49.5%, 39.6%, and 40.0%, respectively, and these serial decreases in prevalence over 8 years were statistically significant (p<0.001). Regardless of sex, age or EGD findings, the prevalence of H. pylori infection was significantly decreased. In the analysis of the H. pylori infection-related factors in 2005, only age and EGD findings (peptic ulcer diseases) were significant factors. CONCLUSIONS: The prevalence of H. pylori infection was significantly decreased during 8-year period in Korean health check-up subjects. Age and peptic ulcer diseases were the two significant factors related to H. pylori infection in Korea.


Subject(s)
Helicobacter Infections/epidemiology , Helicobacter pylori , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Demography , Endoscopy, Digestive System , Female , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Humans , Korea , Male , Middle Aged , Peptic Ulcer/etiology , Prevalence , Retrospective Studies
19.
Public Health Nutr ; 12(8): 1234-41, 2009 Aug.
Article in English | MEDLINE | ID: mdl-18950544

ABSTRACT

OBJECTIVE: Zn deficiency may be widespread in Asian countries such as South Korea. However, dietary habits have changed in response to rapid economic growth and globalization. Zn nutrition in South Koreans has therefore been assessed during a period (1969-1998) of unprecedented economic growth. DESIGN AND METHODS: Cross-sectional food consumption data from the Korean National Nutrition Survey Reports (KNNSR) of South Korea at four separate time points (1969, 1978, 1988 and 1998) were used to calculate Zn, Ca and phytate intakes using various food composition tables, databases and literature values. Nutrient values in local foods were cited from their analysed values. RESULTS: Average Zn intake was 5.8, 4.8 and 5.3 mg/d for 1969, 1978 and 1988 respectively, increasing to 7.3 mg/d in 1998 (73 % of the Korean Dietary Reference Intake). The phytate:Zn molar ratio decreased from 21 to 8 during the study period. Dietary Zn depletion due to marked decreases in cereal consumption, particularly barley which has a low Zn bioavailability, was counterbalanced by marked increases in the consumption of meat and fish, which are also Zn-rich foods. Reduced phytate consumption coincident with increased Zn intake suggests that Zn bioavailability also improved, particularly by 1998. CONCLUSIONS: Although total Zn intake was not greatly affected over the initial period of economic growth in South Korea (1969-1988), Zn contributions from different food sources changed markedly and both Zn intake and potential bioavailability were improved by 1998. The study may have implications for Zn nutrition in other Asian countries currently experiencing rapid economic growth.


Subject(s)
Diet/economics , Phytic Acid/administration & dosage , Trace Elements/deficiency , Zinc/deficiency , Animals , Biological Availability , Cross-Sectional Studies , Edible Grain , Fishes , Hordeum , Humans , Internationality , Korea/epidemiology , Malnutrition/epidemiology , Meat/economics , Seafood/economics , Trace Elements/administration & dosage , Trace Elements/economics , Trace Elements/pharmacokinetics , Zinc/administration & dosage , Zinc/economics , Zinc/pharmacokinetics
20.
Dig Dis Sci ; 54(11): 2434-40, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19093201

ABSTRACT

BACKGROUND: Although the diagnostic and therapeutic values of double balloon endoscopy (DBE) have been investigated, the subjective tolerability to DBE has not been assessed. We aimed to evaluate patients' tolerability to DBE. METHODS: We prospectively enrolled patients who underwent DBE. For the comparison of tolerability to DBE with that to esophagogastroduodenoscopy (EGD) and colonoscopy, those who had not undergone EGD nor colonoscopy were excluded. A total of 52 patients were included. All procedures were performed under conscious sedation with midazolam with or without pethidine. Patients' tolerability to DBE, EGD, and colonoscopy was assessed through an interview with a questionnaire using a 10-point Likert scale. RESULTS: A total of 36 patients underwent both antegrade DBE and EGD under conscious sedation. The level of abdominal pain during procedures, the level of post-procedural abdominal discomfort, and the proportion of patients with persistent abdominal discomfort until the next morning were higher in antegrade DBE. However, when analyzed in 16 patients who had good quality of sedation, the differences in the level of abdominal pain during procedures and the persistent abdominal discomfort until the next morning disappeared. A total of 23 patients underwent both retrograde DBE and colonoscopy under conscious sedation. Tolerability parameters were not different between retrograde DBE and colonoscopy. Serious complications, including hemodynamic instability, did not occur during all procedures. CONCLUSION: Patients tolerated DBE well. DBE may be performed as comfortably as EGD and colonoscopy if the quality of sedation is good enough.


Subject(s)
Endoscopy, Digestive System/adverse effects , Adolescent , Adult , Endoscopy, Digestive System/methods , Female , Humans , Male , Middle Aged , Patient Satisfaction , Pilot Projects , Prospective Studies , Surveys and Questionnaires , Young Adult
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