Probe development for detection of TERRA 1 intramolecular G-quadruplex formation using a fluorescent adenosine derivative.

We developed a probing system to detect the intramolecular G-quadruplex of telomeric repeat-containing RNA (TERRA 1). We used a fluorescent adenosine derivative rA(py) as a fluorophore and incorporated it into the dangling position of the parallel-type G-quadruplex sequence of TERRA 1. The rA(py)-modified G-quadruplex structure exhibited a strong fluorescence emission signal, while the emission signals of the single-strand and duplex structures were much lower.

Effect of different forms of anionic nanoclays on cytotoxicity.

Anionic nanoclays, so-called layered double hydroxide (LDH) nanoparticles, have been extensively applied as drug delivery systems, since they efficiently enter cells via endocytosis pathway and possess controlled release property. However, the stability of LDHs varies, depending on the type of interlayer anions, which can also affect their toxicity. In this study, we investigated the effects of two different forms of LDH, carbonate form (MgAl-LDH-CO3) and chloride form (MgAl-LDH-Cl), on cytotoxicity in human lung epithelial cells. The result showed that MgAl-LDH-Cl was more easily dissolved into metal ions under simulated lysosomal (pH 4.5) and body fluid (pH 7.4) conditions than did MgAl-LDH-CO3. According to cytotoxicity evaluation, MgAl-LDH-CO3 exhibited high toxicity compared with MgAl-LDH-Cl in terms of induction of oxidative stress, apoptosis and membrane damage. These results suggest that easily dissoluble MgAl-LDH-Cl has low cytotoxicity, while high stability of MgAl-LDH-CO3 is correlated to elevated cytotoxicity.

Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells.

The increased applications of nanoparticles in a wide range of industrial fields raise the concern about their potential toxicity to human. The aim of this study was to assess and compare the toxicity of four different oxide nanoparticles (Al2O3, CeO2, TiO2 and ZnO) to human lung epithelial cells, A549 carcinoma cells and L-132 normal cells, in vitro. We focused on the toxicological effects of the present nanoparticles on cell proliferation, cell viability, membrane integrity and oxidative stress. The long-term cytotoxicity of nanoparticles was also evaluated by employing the clonogenic assay. Among four nanoparticles tested, ZnO exhibited the highest cytotoxicity in terms of cell proliferation, cell viability, membrane integrity and colony formation in both cell lines. Al2O3, CeO2 and TiO2 showed little adverse effects on cell proliferation and cell viability. However, TiO2 induced oxidative stress in a concentration- and time-dependent manner. CeO2 caused membrane damage and inhibited colony formation in long-term, but with different degree depending on cell lines. Al2O3 seems to be less toxic than the other nanoparticles even after long time exposure. These results highlight the need for caution during manufacturing process of nanomaterials as well as further investigation on the toxicity mechanism.

Bowel loop in an ovarian tumor: grossly visible, completely developed intestinal loop in mature cystic teratoma of malignant mixed germ cell tumor.

Although a gastrointestinal-type epithelium is observed in 7-13% of mature cystic teratoma cases, the occurrence of a grossly visible, organized gastrointestinal loop formation is very rare. Presented here is the case of a 14-year-old girl with malignant mixed germ cell tumor in the ovaries. In her left ovary a grossly visible, intestinal loop, 9 cm long, with hanging mesentery attached to the cystic wall of a mature cystic teratoma associated with a yolk sac tumor was observed, and in her right ovary another mature cystic teratoma was observed. Microscopy of the intestinal loop indicated a well-organized, intact layer of small intestinal wall. The yolk sac tumor predominantly had a poly-vitelline pattern. Previously, gastrointestinal wall or epithelium that was identified on microscopy has been reported. To the authors' knowledge this is the first case report of the formation of a grossly visible, completely developed intestinal loop in a malignant mixed germ cell tumor.

Seasonal and annual changes in PAH concentrations in a remote site in the Pacific Ocean.

This paper reports the long term observation of particle-associated polycyclic aromatic hydrocarbons (PAHs) at Cape Hedo Atmosphere and Aerosol Monitoring Station, a remote site in the Western Pacific Ocean, from 2008 to 2015. This is the first long-term study that evaluated the contribution of long-range transport of PAHs in East Asia. No obvious trend (P > 0.05) was found in a particular season over the years. However, there are seasonal variations of PAH concentrations with higher in spring and winter. The higher PAH are attributed to air masses from the area including part of China. Source apportionment using three different approaches, i.e., PAH compositional pattern analysis, PAH diagnostic ratio analysis and positive matrix factorization modeling, showed the combined high contribution of biomass burning (18%, 14%) and coal combustion (33%, 24%) in spring and winter. In addition, the contribution of ship emissions (35%) was relatively high in spring, whereas that of vehicle emissions (36%) was relatively high in winter. The contribution of coal combustion to PAH has decreased throughout the years, likely due to changes in energy structure in China. The contribution of biomass burning to PAH has showed no trend, being stable, and that of vehicular emissions has increased.

Serum BAFF predicts prognosis better than APRIL in diffuse large B-cell lymphoma patients treated with rituximab plus CHOP chemotherapy.

OBJECTIVES: B-cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) regulate survival and proliferation of B cells. Thus the association of elevated serum levels of BAFF and APRIL with worse prognosis has been suggested in B-cell lymphoid malignancies. However, the prognostic relevance of BAFF and APRIL is unknown in patients treated with rituximab, a monoclonal antibody targeting B-cell depletion. METHODS: We measured serum levels of BAFF and APRIL by enzyme-linked immunosorbent assay in 66 patients newly diagnosed as diffuse large B-cell lymphoma (DLBCL). All patients were treated with rituximab-CHOP chemotherapy. RESULTS: The mean (+/-standard deviation) serum level of BAFF (1 970.21 +/- 1 979.45 pg/mL) was higher in DLBCL than in controls (861.03 +/- 194.92 pg/mL, Mann-Whitney U-test, P < 0.001). When the patients were dichotomized into high and low BAFF group based on the median value (1 258.00 pg/mL), high BAFF group had less numbers of complete responders to rituximab-CHOP, and more relapses or progression after or during treatment. In multivariate analysis, serum BAFF was an independent prognostic factor for overall survival and progression-free survival (P < 0.05). Although serum levels of APRIL was also higher than controls (10.60 +/- 19.08 ng/mL vs. 1.10 +/- 0.30 ng/mL, P = 0.023), it failed to show prognostic significance. CONCLUSIONS: Serum BAFF may be a useful indicator predicting prognosis in DLBCL patients treated with rituximab-containing chemotherapy.

Increased serum 90K and Galectin-3 expression are associated with advanced stage and a worse prognosis in diffuse large B-cell lymphomas.

The role of 90K and galectin-3 in cell-to-extracellular matrix adhesion and tumor metastasis has been reported, but little is known about their role in the prognosis and extranodal involvement of diffuse large B-cell lymphomas (DLBCL). Thus, we measured serum 90K concentration by enzyme-linked immunosorbent assay and tissue expression of galectin-3 by immunohistochemistry in newly diagnosed DLBCL patients. The mean serum 90K concentration was higher in DLBCL than in healthy controls (1,408.81 +/- 89.45 vs. 980.94 +/- 58.69 ng/ml, p = 0.036). High serum 90K (median value >or=1,249.50 ng/ml) and high galectin-3 expression (grade 3 positive staining in >75% of cells) showed a significant association with stage III/IV, >or=2 extranodal involvements and risk of high/high-intermediate international prognostic index (p < 0.05). The complete response (CR) rate (86.9%, 20/23) in the low 90K group was higher than in the high 90K group (56.5%, 13/23). Among 14 patients with high galectin-3 expression, only 6 patients showed CR (42.9%). The time to progression and overall survival were shorter in the group with high 90K and galectin-3 expression (p < 0.05). In conclusion, serum 90K and galectin-3 expression might be useful markers to indicate the extent of lymphoma involvement and prognosis in DLBCL.

Light-Triggered Radiochemical Synthesis: A Novel 18F-Labelling Strategy Using Photoinducible Click Reaction to Prepare PET Imaging Probes.

Novel probe development for positron emission tomography (PET) is leading to expanding the scope of molecular imaging. To begin responding to challenges, several biomaterials such as natural products and small molecules, peptides, engineered proteins including affibodies, and antibodies have been used in the development of targeted molecular imaging probes. To prepare radiotracers, a few bioactive materials are unique challenges to radiolabelling because of their complex structure, poor stability, poor solubility in aqueous or chemical organic solutions, and sensitivity to temperature and nonphysiological pH. To overcome these challenges, we developed a new radiolabelling strategy based on photoactivated 1,3-dipolar cycloaddition between alkene dipolarophile and tetrazole moiety containing compounds. Herein, we describe a light-triggered radiochemical synthesis via photoactivated click reaction to prepare 18F-radiolabelled PET tracers using small molecular and RGD peptide.

Protective Effect of BLED-exposed Conditioned Media on Cell Injury.

Previous studies have reported that 450 nm blue light emitting diode (BLED) induces apoptosis through a mitochondria-mediated pathway in cancer cells and reduces the early stage tumor growth. This study was performed to determine the effects of BLED-irradiated cell metabolites on cell injury. Our results showed that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM) inhibited apoptosis and increased cell survival. Cell protection-related proteins were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF analysis. Treatment with LCM inhibited apoptotic cell death and increased the live cell population. The cellular protective effect of LCM was associated with keratin and collagen type VI secretion from cells after low dose of BLED irradiation. Interestingly, expression of endoplasmic reticulum stress proteins was dose dependently increased after 4 h BLED irradiation. Only levels of BiP, CHOP and ERO1-Lα were decreased significantly after 24 h incubation, indicating their anti-apoptotic property in these cells. These results indicated that cell metabolites stimulated by low-dose BLED irradiation have a cytoprotective effect on cell injury via increasing transient intracellular ER stress. Further studies remain to provide the molecular mechanisms of LCM for cytoprotective activity.

Synthesis and Evaluation of 2-[18F]Fluoroethyltriazolesuberohydroxamine Acid for Histone Deacetylase in a Tumor Model as a Positron Emission Tomography Radiotracer.

Histone deacetylases (HDACs) are an important regulator of expression and activity of numerous proteins in terms of epigenetic aberrations. This makes HDACs attractive for antitumor therapy and imaging in certain cancers. The authors report the radiochemical synthesis of 2-[18F]fluoroethyltriazolesuberohydroxamine acid ([18F]FETSAHA) as a HDAC-targeted radiolabel probe for positron imaging tomography/computed tomography. The authors also evaluated the in vivo tumor targeting in subcutaneously implanted RR1022 rats. [18F]FETSAHA was produced in less than 2 h with 31.2% ± 4.6% (n = 6) decay-corrected yields and specific activity of 21.4 ± 9.1 GBq/µmol (n = 6) at end of synthesis. [18F]FETSAHA showed significant radioactivity accumulation in tumors with rapid blood clearance and both gastrointestinal track and renal excretion. Tumor-to-blood and tumor-to-muscle uptake ratios in the RR1022 tumor bearing rat model were 1.21 and 1.83 and 2.75 and 2.76 at 30 and 60 min, respectively. An inhibition study of [18F]FETSAHA in the presence of excess amount of suberanilohydroximic acid (SAHA) revealed receptor specific activity accumulation. [18F]FETSAHA has favorable in vivo tumor imaging properties and may be useful for noninvasive evaluation of the correlation between cancer and HDACs.

Evaluation of gas permeation barrier properties using electrical measurements of calcium degradation.

In this work, we developed a thin calcium degradation method introducing sensitive electrical resistance monitoring. We have demonstrated structural models of the inorganic/organic thin films to evaluate barrier properties against water and oxygen permeation. The time-dependent transmission curve of a multibarrier coated on both sides of the polyethersulfone substrate had a linear slope which was measured as 5.17 x 10(-3) gm(2) day at 20 degrees C and 60% relative humidity. This system can measure an accurate permeation rate with a high sensitivity in the measurable range of 10(1)-10(-6) gm(2) day. In addition, the test structure devised is applicable to various fabrication techniques for passivation layers with durability and ultralow permeability for flexible organic light emitting diodes.

Treatment outcome of front-line systemic chemotherapy for localized extranodal NK/T cell lymphoma in nasal and upper aerodigestive tract.

We analysed the treatment outcome of localized extranodal NK/T cell lymphoma initially treated with CEOP-B chemotherapy based on the primary site of involvement (nasal cavity vs. upper aerodigestive tract) and treatment modality (chemotherapy vs. chemotherapy followed by radiotherapy. Forty-three patients newly diagnosed as extranodal NK/T cell lymphoma were analysed: 29 cases from nasal cavity/nasopharynx and 14 from upper aerodigestive tract. Twenty-six patients were treated with chemotherapy alone, while adjuvant radiotherapy was given to 17 patients. Overall response rate to front-line CEOP-B chemotherapy was 67.4% (29/43) and the complete remission (CR) rate was 44.2% (19/43). Median overall and disease-free survival was 26.87 months [95% confidence interval (CI) = 8.71 - 45.03] and 15.27 months (95% CI = 2.92 - 27.62). The responders (CR or partial response) to initial CEOP-B chemotherapy showed longer overall survival than non-responders (P = 0.0026). Local relapse was observed to be higher in the chemotherapy alone group compared to the chemoradiotherapy group. Adjuvant radiotherapy failed to improve survival; thus, the median disease-free survival of the chemotherapy and chemoradiotherapy groups was not different (P = 0.9101). There may be a tendency for better overall survival in group of upper aerodigestive tract lymphoma than the nasal cavity/nasopharynx group (P = 0.0643). However, front-line CEOP-B chemotherapy has a limited role and adjuvant radiotherapy failed to improve survival in localized extranodal NK/T cell lymphoma.

Development and application of three-dimensional potential source contribution function (3D-PSCF).

A potential source contribution function (PSCF) can indicate the source areas of high air pollutant concentrations using backward trajectories. However, the conventional two-dimensional PSCF (2D-PSCF) cannot consider the emission and transport height of air pollutants. That missing information might be critical because injection height varies depending on the source type, such as with biomass burning. We developed a simple algorithm to account for the height of trajectories with high concentrations and combined it with the conventional PSCF to devise 3D-PSCF. We demonstrate the applicability of the 3D-PSCF by applying it to particulate PAH data collected from September 2006 to August 2007 in Seoul. We found variation in the results from 3D-PSCF with threshold heights from 3,000 to 1,500 m. Applying 2,000 m as the threshold height in the PSCF calculation most clearly determined the possible source areas of air pollutants from biomass fuel burning that were affecting the air quality in Seoul.

Paratubal Borderline Malignancy: A Case of a 17-Year-Old Adolescent Female Treated with Laparo-Endoscopic Single-Site Surgery and a Review of the Literature.

BACKGROUND: Although paratubal cysts are common, borderline paratubal cysts are extremely rare. We describe the case of a large borderline paratubal cyst in a 17-year-old adolescent female treated with laparo-endoscopic single-site surgery (LESS), and review the literature. CASE: A 17-year-old female was referred due to a large right adnexal cyst on pelvic sonogram. A CT scan showed a 19-cm cystic lesion with enhancing papillary projection along the wall. Laparo-endoscopic single-site surgery confirmed a large cystic mass that originated from the right salpinx. Right salpingectomy and right ovarian wedge resection were performed, and intraoperative frozen section analysis was conducted. The result of the frozen section analysis and final pathologic review indicated that the cyst was a serous papillary-type borderline tumor in a paratubal cyst. SUMMARY AND CONCLUSION: To the best of our knowledge, this is the first case report of a BPC treated with LESS. We suggest that minimally invasive, fertility-preserving surgery should be considered as a standard treatment of borderline paratubal cysts if patients desire future fertility.

Genotoxic evaluation of the biocomponents of the cricket, Gryllus bimaculatus, using three mutagenicity tests.

The mutagenic potential of the extracted components of Gryllus bimaculatus, a species of cricket, was evaluated using short-term genotoxicity tests including the Ames, chromosome aberration, and micronuclei tests. In a Salmonella typhimurium assay, G. bimaculatus extract did not produce any mutagenic response in the absence or presence of S9 mix with TA98, TA100, TA1535, and TA1537. Chromosome aberration testing showed that G. bimaculatus had no significant effect on Chinese hamster ovary (CHO) cells. In the mouse micronucleus test, no significant alteration in occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice intraperitoneally administered with G. bimaculatus extract at doses of 15, 150, or 1500 mg/kg. These results indicate that G. bimaculatus extract exerts no mutagenic effect in these in vitro and in vivo systems.

Mesenteric Castleman's disease.

We report here a rare case of mesenteric Castleman's disease presenting as a mesenteric mass. A 13-year-old female child was admitted to our hospital complaining of intermittent vague abdominal pain. She had hypochromic anemia, thrombocytosis and an elevated erythrocyte sedimentation rate (ESR). Ultrasonography and computed tomography indicated an intra- abdominal mass might represent a lymphoma or gastrointestinal stromal tumor or leiomyoma, but the definitive preoperative diagnosis couldn't be confirmed. The surgical resection of the mass revealed the mesenteric hyaline vascular-type Castleman's disease.

Accuracy and reproducibility of telecytology diagnosis of cervical smears. A tool for quality assurance programs.

We randomly selected 50 cervical smears (benign, 14; atypical squamous cells of undetermined significance [ASCUS], 5; low-grade squamous intraepithelial lesion [LSIL], 10; high-grade squamous intraepithelial lesion (HSIL), 12; squamous cell carcinoma, 6; adenocarcinoma, 3) and captured 1,181 digital images (518 MB) at a maximum resolution of 1,600 x 1,200 pixels and transmitted them by e-mail. Diagnosis of glass slides and digital images was done independently in a double-blind manner by 3 pathologists and 3 cytotechnologists, commencing with the diagnosis of digital images followed by diagnosis of glass slides 3 months later. The procedure was repeated after 3 months. Diagnoses were recorded as benign, ASCUS or atypical glandular cells of undetermined significance, LSIL, HSIL, squamous cell carcinoma or adenocarcinoma, and "inadequate for diagnosis." Diagnostic accuracy and interobserver reproducibility were analyzed using an intraclass correlation coefficient (ICC), which revealed good interobserver agreement for the first (0.72) and second (0.64) glass slide diagnoses and the first (0.72) and second (0.60) digital image diagnoses. The kappa values for intraobserver variation between first and second glass slide diagnoses and first and second digital image diagnoses showed moderate to excellent agreement. Digital images are suitable substitutes for glass slides; telecytology can be used as an alternative method for the cytologic diagnosis of cervical smears, particularly in quality assurance programs.

NK/T-cell lymphoma associated with Epstein-Barr virus in a patient infected with human immunodeficiency virus: an autopsy case.

Natural killer (NK)/T-cell lymphoma associated with Epstein-Barr virus (EBV) in a patient infected with human immunodeficiency virus (HIV) is very rare. The authors encountered a case of NK/T-cell lymphoma in a 36-year-old man who presented with an ulcerative mass on both tonsils. During assessment, HIV positivity was noted. The EBV was detected by EBV-encoded RNA 1 messenger RNA in situ hybridization and polymerase chain reaction for EBV-encoded nuclear antigen 1. On immunohistochemical staining, the infiltrated lymphoid cells of the tonsils demonstrated positvity for CD3, CD56, UCHL1, and granzyme, a finding compatible with NK/T-cell lymphoma. The patient received radiation therapy and chemotherapy, but died as a result of opportunistic infection of invasive aspergillosis after tumor recurrence. An autopsy was done with the consent of the patient's family. To our knowledge, this is the first case in an HIV patient of NK/T-cell lymphoma of the tonsils associated with EBV, confirmed by autopsy. NK/T-cell lymphoma should be considered in the HIV-positive patients with an ulcerating tonsillar mass.

Genotoxicity evaluation of Isaria sinclairii (ISE) extract.

The mutagenic potential Isaria sinclairii, a traditional Chinese medicine composed of the fruiting bodies of I. sinclairii and its parasitic host larva, was evaluated using short-term genotoxicity tests, namely, the Ames test, chromosome aberration (CA), and micronuclei (MN) tests. In a Salmonella typhimurium assay, I. sinclairii extract (ISE) did not produce any mutagenic response in the absence or presence of 59 mix with TA98, TA100, TA1535, and TA1537. In the chromosome aberration (CA) test, ISE induced no significant effect on Chinese hamster ovary (CHO) cells compared with control. In the MN test, no significant change in the occurrence of micronucleated polychromatic erythrocytes was observed in male ICR mice intraperitoneally administered ISE at doses of 15, 150, or 1500 mg/kg. These results indicate that ISE has no mutagenic potential in these in vitro and in vivo systems.

Imaging findings of Castleman's disease localized in the axilla: a case report.

Castleman's disease is a rare benign lymphoproliferative disorder of uncertain origin which most commonly involves the mediastinum but rarely affects the axilla. We report a case of localized Castleman's disease involving the axillary lymph node. Mammography revealed a well-defined, homogeneously dense ovoid mass, 3 cm in size, in the left axilla, while gray-scale ultrasonography (US) demonstrated a well-defined, uniformly hypoechoic ovoid mass with good through transmission. Peripheral hypervascularity was observed at power Dopper US, and early rapid homogeneous enhancement at contrast-enhanced dynamic CT.