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The mechanism that leads to a decrease in β1-adrenergic receptor (β1AR) expression in the failing heart remains uncertain. This study shows that cardiomyocyte β1AR expression and isoproterenol responsiveness decrease in response to oxidative stress. Studies of mechanisms show that the redox-dependent decrease in β1AR expression is uniquely prevented by carvedilol and not other βAR ligands. Carvedilol also promotes the accumulation of N-terminally truncated β1ARs that confer protection against doxorubicin-induced apoptosis in association with activation of protein kinase B. The redox-induced molecular controls for cardiomyocyte β1ARs and pharmacologic properties of carvedilol identified in this study have important clinical and therapeutic implications.

A tracer dispersion experiment was conducted at the Wolsong Nuclear Power Plant, Korea to determine concentrations of airborne radioactive materials under weather conditions unfavorable to dispersion. The observed concentrations were compared with estimates from a Gaussian plume model to determine whether the model provides sufficiently conservative estimation under bad weather conditions and is therefore suited to radiological impact analysis at nuclear power facilities. It was found that the more often the meteorological data was used, the more advantageous it was in helping to understand the diffusion characteristics of radioactive materials. Most of the current computer models for estimating the dispersion of airborne radioactive materials, which are needed to gain construction approval for a nuclear power plant, are based on the Gaussian plume model. Overall, the Gaussian plume model overestimates the concentration of airborne radioactive materials compared with actual observations. This suggests that the model is suitably conservative to enable its use in radiological environmental impact assessment of the health risks to nearby communities.

This study identified the terrain and building effects on the atmospheric dispersion of radioactive materials at the Wolsong Nuclear Site. To analyze the atmospheric dispersion of radioactive materials, the AERMOD-PRIME model, CFD model and meteorological data from 2010 were used. The terrain and building effects on the atmospheric dispersion of radioactive materials within a 1 km radius of the site were statistically significant. The maximum concentration of the radioactive material increased by 7 times compared to the concentration when the terrain and building effects were not considered. It was found that the terrain and building influenced the decrease in the concentration of radioactive material in a concentric circle with a 914 m radius from the center of the site. The concentration of radioactive material in a concentric circle with a 350 m radius was two-times higher than the concentration estimated at the backside of the building, which is the downwind side, without any consideration of the terrain and building effects. In consideration of the Korean situation, in which multiple nuclear reactors are built on the same nuclear site, it is necessary to evaluate the risk that may affect workers and nearby residents by reflecting the terrain and building effects.

Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/β-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of β-catenin, WIF-1, GLI2, androgen receptor, and epithelial-mesenchymal transition-related markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.

This study quantified the characteristics of atmospheric dispersion and exposure dose of radioactive materials in four power plant sites in Korea. As a tool to quantify atmospheric dispersion, this study used air concentrations based on an assumed unit release of radioactivity per time. The disparities in atmospheric dispersion degrees among the sites were tested statistically with an analysis of variance (ANOVA). The probabilistic distribution of exposure dose in consideration of meteorological conditions in the case of a nuclear accident was estimated with a Monte Carlo simulation. The Yeoungkwang nuclear site on the west coast was the poorest in dispersion, whereas the most active dilution of radioactive materials took place in the Kori nuclear site located on the east coast on an annual basis. In case of an accident with the worst conditions of atmospheric dispersion, assuming the emission rate was 1 Bq/s and the duration time of the accident is 1 h, the highest 99.5th percentile of dose–1.51E−14 mSv.

The effects of wind speed defined for calm conditions and wind interval at a low wind speed on the atmospheric dispersion factors (ADFs) using a Gaussian plume model, statistical approach, and XOQDOQ program were analyzed in this study. There was a statistically significant difference in the ADFs calculated on 1000-m concentric circles from the release when the wind speed is adjusted from 0.5 m/s to 0.2 m/s for calm conditions. If a dispersion model as the input of the joint frequency distribution is used for an estimation of ADFs, it was found that the ADFs were affected by the classification of wind intervals at a low wind speed of lower than 2.0 m/s. To minimize the effect of wind speed intervals at a low wind speed to ADFs, the wind interval should be adjusted considering the frequency distribution of a low wind speed and adjusted in either way to narrow the interval for a low wind speed or widen it for a high wind speed.

Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a pungent ingredient of hot chili peppers, has been reported to possess substantial anticarcinogenic and antimutagenic activities. In the present study, we investigated the effect of capsaicin on induction of apoptosis in highly metastatic B16-F10 murine melanoma cells. Capsaicin inhibited growth of B16-F10 cells in a concentration-dependent manner. Proapoptotic effect of capsaicin was evidenced by nuclear condensation, internucleosomal DNA fragmentation, in situ terminal nick-end labeling of fragmented DNA (TUNEL), and an increased sub G1 fraction. Treatment of B16-F10 cells with capsaicin caused release of mitochondrial cytochrome c, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase in a dose-dependent manner. Furthermore, Bcl-2 expression in the B16-F10 cells was slightly down-regulated by capsaicin treatment. In contrast, there were no alterations in the levels of Bax in capsaicin-treated cells. Collectively, these findings indicate that capsaicin-induces apoptosis of B16-F10 melanoma cells via down-regulation the Bcl-2.

Detection and analysis of DNA adducts resulting from endogenous or exogenous exposures to carcinogens are essential not only for quantifying biologically effective doses but also for establishing relationships between exposure and cancer risk. We have developed and validated a procedure of high sensitivity and specificity based on fluorescence labeling of DNA adducts combined with high-performance liquid chromatography-laser-induced fluorescence detection. The fluorescent dye 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionic acid (BODIPY FL) was used to label the deoxynucleoside adducts N-(2'-deoxyguanosine-8-yl)-4-aminobiphenyl and N-(2'-deoxyguanosine-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and the base adduct aflatoxin B(1)-formamidopyrimidine by acylation. The labeling reaction was carried out on adducts at 1pmol to 30nmol concentrations at 25 degrees C for 4h in dichloromethane with 200- to 5000-fold excess of BODIPY FL. BODIPY FL and its activating agents 1,3-dicyclohexylcarbodiimide and 4-dimethylaminopyridine were used at a molar ratio of 1:2:2. Under these conditions, all of the above adducts were quantitatively converted to bis-labeled products, as confirmed by mass spectrometry. Sites of derivatization of adduct deoxynucleosides were established primarily by nuclear magnetic resonance and by collision-induced dissociation mass spectrometric analysis, which indicated that the bis-BODIPY groups were located predominantely on the 3'- and 5'-hydroxyl groups of the deoxyribose ring.

Objectives This study was conducted to evaluate a clinical efficacy of human papillomavirus (HPV) oligonucleotide microarray (Biomedlab Co., Seoul, South Korea) for the detection of HPVs in various cervical lesions. Methods HPV DNAs from 234 patients were analysed by two methods. Among those, 212 patients were classified into 5 groups according to the histologic diagnosis: chronic cervicitis, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and invasive cervical carcinoma. PCR-RFLP could detect 7 types of high-risk HPVs (HPV 16/18/31/33/35/52/58) and HPV microarray could detect 15 types of high-risk HPVs (HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68/69) and 7 types of low-risk HPVs (HPV 6/11/34/40/42/43/44). Results HPV genotyping by HPV oligonucleotide microarray revealed that HPV16 was the most frequent type (30.2%) in all specimens tested and was significantly more frequent in CIN III and invasive carcinomas than other lesions. HPV DNAs were detected in 158 and 174 of the 234 cervical samples by PCR-RFLP and HPV microarray, respectively. The correlation between the two methods was good in detecting HPVs in general (kappa index=0.69) and HPVs 31 and 52 (kappa index=0.70 and 0.70, respectively) and excellent in detecting HPVs 16, 18, 33, 35, and 58 (kappa index=0.90, 0.88, 0.92, 0.77, and 0.84, respectively). Double HPV infection was detected in 10 cases and one triple infection was detected. By combining cytology and HPV testing, the sensitivity was improved to 87.5, 95.5, 96.1, and 97.2% in CIN I, CIN II, CIN III, and carcinoma, respectively. Conclusions This results suggest that HPV oligonucleotide microarray is a highly comparable method to the previously used PCR-RFLP method for the detection of HPVs in cervical specimens. Genetic informations for HPV infection in cervical specimens may offer new strategies in manipulating the patients harboring cervical intraepithelial neoplasia and cervical carcinoma.

In this study we examined the use of a new-human papillomavirus (HPV) detection method, the HPV oligonucleotide microarray system (Biomedlab Co., Korea), which we compared with the well-established HPV DNA detection system (Hybrid Capture II; HC-II, Digene Co.). This new method prompted us to develop a new HPV genotyping technique, using the oligonucleotide microarray, to detect the generic and type-specific sequence of HPV types. In particular, we undertook the evaluation of the clinical efficacy of the HPV oligonucleotide microarray for detecting HPV in cervical neoplastic lesions.One hundred forty patients were involved and classified into three groups according to their histopathologic diagnoses: Group I (nonspecific chronic cervicitis; n = 61), Group II (low-grade squamous intraepithelial lesion (SIL); koilocytosis, and mild dysplasia; n = 39), and Group III (high-grade SIL; moderate, severe dysplasia and in situ carcinoma; n = 40). Cytological diagnoses were based on the Bethesda System and cervical samples were analyzed by the two methods. The HPV oligonucleotide microarray detected 15 types of high-risk HPV (HPV-16/-18/-31/-33/-35/-39/-45/-51/-52/-56/-58/-59/-66/-68/-69) and 7 types of low-risk HPV (HPV-6/-11/-34/-40/-42/-43/-44).In 105 of the 140 cervical samples (75%), HPV DNAs were examined using the HC-II method. HPV detection rates using the HPV microarray agreed with those of HC-II. One HC-II-positive, but HPV microarray-negative, case occurred in the low-grade SIL (Group II) and was later confirmed negative for HPV. The other HPV microarray-positive but HC-II-negative case was found to be HPV-18 by PCR. Low-risk types of HPV were detected in 3 of 39 low-grade SIL cases (Group II) using the HPV microarray. HPV-16 was the most frequent type (32.1%) in all specimens tested, and was significantly more frequent in low-grade or high-grade intraepithelial lesions (Groups II or III) than in normal controls (Group I) (P0.05). HPV-58 was the second most common type (17.5%) in Group III. The HPV microarray was found to have advantages in terms of identifying the HPV genotypes and cases of multiple HPV infection. Double HPV infections were detected in 12 cases and triple HPV infections in 7 cases. Two cases were positive for four types of HPV (HPV-16/18/33/35, HPV-16/18/58/68). The sensitivity of HPV testing (HC-II; 94.9%, HPV microarray; 93.7%) for identifying patients with squamous intraepithelial lesion was significantly better than the sensitivity of cytology (77.1%, P0.05). On using multiple logistic regression analysis to estimate the relative risk of SIL versus HPV type, HPV-16-positive cases were found to have a 7.5-fold risk of SIL (95% CI = 3.28-16.51; P0.01). HPV-33 and HPV-58 were found to be significantly related to high-grade SILs (P0.01).Our results suggest that the HPV oligonucleotide microarray is highly comparable to HC-II for detecting HPV in cervical specimens. The HPV oligonucleotide microarray provides useful information on viral genotype and multiple HPV infections in HPV-related cervical lesions. Genetic information on HPV in cervical specimens might be a particular benefit of the new procedure in the management of cervical neoplastic lesions

The synthesis of the reactive acetates, trans -3-acetoxy-2-hydroxy- N -nitrosomorpholine 3 and N -(1-acetoxy-2-hydroxyethyl)- N -nitrosoethanolamine 12, of two α-hydroxynitrosamines has been accomplished through the ring opening of the corresponding epoxides, NEMOR and 10 which were prepared by dimethyldioxirane oxidation of the vinyl nitrosamines.