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The purpose of this study is to evaluate Aldo Rossi`s work as representation or non-representation, for some hold that the works of Aldo Rossi are representative and others say that they are non-representative. According to the three kinds of novelties appearing after Stephen Pepper`s concept, "the breaking of reference" happens, and Aldo Rossi`s concept, "the sense of deposition" Rossi`s work is uncovered as non-representation. In order to clarify Rossi`s work as non-representation, we are going to borrow Pepper`s terms, intrusive novelty, emergent novelty, and naive novelty. The breaking of reference accompanies intrusive novelty to bring a sense of representation, emergent novelty to intuit a sense of non-representation, and naive novelty to a sense of newness of disorder. We hope to verify a hypothesis that Aldo Rossi`s architectural thought and the architecture come from `emergent novelty` on the basis of his two books, A Scientific Autobiography and Architecture of the City. Also this paper discusses qualitative aspects rather than visual aspects. The main concepts of emergent novelty are applied to Aldo Rossi`s works and his thought. Finally this paper verifies `the hypothesis` through revealing what Aldo Rossi means by the quality of suspension, the sense of deposition, and idea of the unfinished(repetition). Rossi`s work is not textural reference of representation appearing after blocking, but qualitative reference of non-representation. more...

Zirconium hydroxide was synthesized by varying the aging time of the zirconyl chloride octahydrate at in aqueous solution and the resulting hydroxides were calcined at for 6 h to obtain the crystalline . The materials used in this study were characterized by differential thermal analysis (DTA), X-ray diffraction (XRD), -sorption, transmission electron microscopy (TEM), temperature-programmed desorption (-TPD), -TPD and iso-propanol TPD analyses to correlate with catalytic activity for the dehydration of iso-propanol. The pure tetragonal phase was obtained after 24 h aging of zirconium hydroxide and successive calcination at . The increase of aging time showed the production of smaller particle size resulting that the higher specific surface area and total pore volume. -TPD results revealed that the relative acidity of the catalysts increased along with the increase of aging time. On the other hand, the results of -TPD showed the reverse trend of -TPD results. The best catalytic activity for the dehydration of iso-propanol to propylene was shown over catalyst aged for 168 h which had the highest (). The catalytic activity could be correlated with high surface area, relative acidity and easy desorption of iso-propanol. more...

Recent studies have shown that a bioactive lipid prostacyclin (PGI2) plays a role in various cancers, including lung cancer. However, the specific function of PGI2 in ovarian cancer progression has not been determined. This study investigated the effects of PGI2 on cell growth, migration, and invasion in ovarian cancer cells using iloprost, a stable PGI2 analog. Iloprost significantly inhibited migration and invasion, but not cell growth, in a dose-dependent manner in human ovarian cancer cells (A2780 and SKOV3). Interestingly, the cell surface Gs protein-coupled PGI2 receptor IP was enhanced in human ovarian cancer cells. The inhibitory effect of iloprost on migration and invasion was entirely reversed by an IP antagonist (CAY10449) and IP siRNA, whereas the knockdown of peroxisome proliferator-activated receptor δ (PPARδ), a nuclear receptor of PGI2, did not rescue the effect of iloprost. Additionally, iloprost markedly decreased the expression of matrix metallopeptidase-2 and -9 (MMP-2 and MMP-9), which may be induced in the process of ovarian cancer metastasis. IP siRNA inhibited iloprost-reduced MMP-2 expression but not MMP-9 expression. Moreover, inhibition of protein kinase A (PKA) and overexpression of Akt and p38 rescued the inhibition of invasion and the reduction of MMP-2 expression by iloprost. Furthermore, iloprost-induced activation of PKA was associated with PKA-mediated Akt and p38 inactivation in ovarian cancer cells. Taken together, these results demonstrate that iloprost inhibits ovarian cancer cell invasion by downregulating MMP-2 expression via the IP-mediated PKA pathway. This study is the first to reveal a novel role for iloprost and to clarify its underlying mechanism in human ovarian cancer cells. more...

：There exist many merits in designing products and setting operational condition when computer aided engineer-ing (CAE) is adopted in injection molding process. CAE also gives increasing efficient of molding, reducing developing time of product, and maintaining high quality products. Specially, it suggests design guidelines for new products and reducingwasting time to get steady state. Two and three dimensional computer simulations are available in injection molding andthose results are somewhat different. However there are no guidelines for 2D and 3D computer simulations in using CAEin injection molding even though it is widely used in plastic industry. In this study, two and three dimensional computationresults were compared for various part thickness, part shape, and number of finite element. Subsequently computationalresults were compared with experimental data such as pressure and temperature. The guidelines in two and three dimensionalCAE analysis have been suggested through this study. more...

Ethnopharmacological relevance Deer antler has been used for centuries as medicine for a wide range of health problems, including various women's diseases. However, there is a safety concern related to its use in hormone-sensitive conditions, such as breast cancer and endometriosis. In the present study, we investigated the effect of deer (Cervus elaphus) antler extract (DAE) on adhesion and migration of human endometriotic cells. Materials and methods Adhesion, wound-healing, and transwell migration assays were performed in endometriotic cells 11Z and 12Z. Expression of matrix metalloproteinase (MMP)-2, MMP-9, TNF-α, and IL-6 were measured by real-time RT-PCR and Western blot analysis. Results DAE (50 and 100 μg/ml) decreased the adhesion of 11Z and 12Z cells on peritoneal mesothelial Met5-A cells. Wound-healing and transwell migration assays revealed that DAE (50 and 100 μg/ml) inhibited migration in 11Z and 12Z cells. It was further demonstrated that treatment with DAE (50 and 100 μg/ml) significantly decreased the levels of MMP-2, MMP-9, TNF-α, and IL-6. Conclusions These results indicate that DAE is a potential anti-endometriotic agent to inhibit the adhesion and migration of endometrial cells through the suppression of various related molecules. more...

This study is the first to investigate the antiproliferative effect of eupatilin in human endometrial cancer cells. Eupatilin, a naturally occurring flavonoid isolated from Artemisia princeps, has anti-inflammatory, anti-oxidative, and anti-tumor activities. In the present study, we investigated the potential effect of eupatilin on cell growth and its molecular mechanism of action in human endometrial cancer cells. Eupatilin was more potent than cisplatin in inhibiting cell viability in the human endometrial cancer cell lines Hec1A and KLE. Eupatilin showed relatively low cytotoxicity in normal human endometrial cells HES and HESC cells when compared to cisplatin. Eupatilin induced G2/M phase cell cycle arrest in a time- and dose-dependent manner, as indicated by flow cytometry analysis. In addition, treatment of Hec1A cells with eupatilin resulted in a significant increase in the expression of p21(WAF1/CIP1) and in the phosphorylation of Cdc25C and Cdc2. Knockdown of p21 using specific siRNAs significantly compromised eupatilin-induced cell growth inhibition. Interestingly, levels of mutant p53 in Hec1A cells decreased markedly upon treatment with eupatilin, and p53 siRNA significantly increased p21 expression. Moreover, eupatilin modulated the phosphorylation of protein kinases ERK1/2, Akt, ATM, and Chk2. These results suggest that eupatilin inhibits the growth of human endometrial cancer cells via G2/M phase cell cycle arrest through the up-regulation of p21 by the inhibition of mutant p53 and the activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway. more...

This study aims to consider the effects of the change in communication culture affected by `Social Media` on the film marketing. Particularly, Twitter, a kind of Social Media which shows the most rapid growth recently, is examined for what kind of benefits it`s functional characteristics would provide for film marketing. Twitter, which has distinctive characteristics such as free access, the high level of attention resulting from its simplicity, alarming speed of spreading information and low costs, offers a variety of marketing opportunities not only for general commercial films but for low budget or independent films that do not have sufficient marketing opportunity. In the case of the documentary film (2010, Woo-jung Kwon), starting from the process of the film production through release to the time after the screening, it continued to communicate with potential audiences via Twitter and tried every tool of film marketing like advertising, PR, promotion and word of mouth. By doing so, it provides a model for low budget or independent films about what alternative activities they might be able to conduct for film marketing. more...

Background Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells). Methods WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B (NF-κB) and p38 and the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, cyclooxygenase (COX)2, and prostaglandin E (PGE)2 were quantified using western blotting and RT-PCR, respectively. Results Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of NF-κB, and expression of COX2 and PGE2 in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of IL-1β and TNF-α expression was also observed with RT-PCR. Conclusion Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings. more...

Background The imbalance between osteoblasts and osteoclasts can lead to pathological conditions such as osteoporosis. It has been reported that opioid adversely affect the skeletal system, but it is inconsistent. Remifentanil is currently used as an adjuvant analgesic drug in general anesthesia and sedation. The aim of the present study was to investigate the effect of remifentanil on the osteoblast differentiation and mechanism involved in this effect. Methods The C2C12 cells (mouse pluripotent mesenchymal cell line) were used as preosteoblast. Osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) staining. C2C12 cell migration by remifentanil was evaluated using Boyden chamber migration assay. The expression of Runx2 and osterix was evaluated by RT-PCT and western blot analysis to investigate the mechanism involved in remifentanil-mediated osteoblast differentiation. Results ALP staining showed that remifentanil increased significantly osteoblast differentiation. In Boyden chamber migration assay, C2C12 cell migration was increased by remifentanil. RT-PCR and western blot analysis showed that the expression of Runx2 and osterix was upregulated by remifentanil. Conclusions We demonstrated that remifentanil increased osteoblast differentiation in vitro by upregulation of Runx2 and osterix expression. Therefore, remifentanil has the potential for assisting with bone formation and bone healing. more...

Let W α be a weighted shift with positive weight sequence α = {α i } ∞i=0 . Thesemi-cubical hyponormality of W α is introduced and some flatness properties of W α arediscussed in this note. In particular, it is proved that if α n = α n+1 for some n ≥ 1, thenα n+k = α n for all k ≥ 1. 1. Introduction and preliminariesLet H be a separable, infinite dimensional, complex Hilbert space and let L(H)be the algebra of all bounded linear operators on H. An operator T in L(H) isweakly n-hyponormal if p(T) is hyponormal for any polynomial p with degree lessthan equal to n. And an operator T is polynomially hyponormal if p(T) is hyponor-mal for every polynomial p. In particular, the weak 2-hyponormality (or weak3-hyponormality) refered to as quadratical hyponormality (or cubical hyponormal-ity, resp.), and has been considered in detail in [5], [6] and [8]. The flatness propertymakes an important role for detecting the bridges between subnormal and hyponor-mal operators. In [10] Stampfli proved that every subnormal weighted shift W more...

The present study examined 469 commercially available fermented alcoholic beverages (FABs), including beer (draft, microbrewed, and pasteurized), fruit wine (grape and others), refined rice wine, and yakju (raw and pasteurized). Samples were screened for Escherichia coli and eight foodborne pathogens (Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, Salmonella spp., Staphylococcus aureus, and Yersinia enterocolitica), and the aerobic plate count, lactic acid bacteria, acetic acid bacteria, fungi, and total coliforms were also enumerated. Microbrewed beer contained the highest number of microorganisms (average aerobic plate count, 3.5; lactic acid bacteria, 2.1; acetic acid bacteria, 2.0; and fungi, 3.6 log CFU/ml), followed by draft beer and yakju (P < 0.05), whereas the other FABs contained , 25 CFU/25 ml microorganisms. Unexpectedly, neither microbial diversity nor microbial count correlated with the alcohol content (4.7 to 14.1%) or pH (3.4 to 4.2) of the product. Despite the harsh conditions, coliforms (detected in 23.8% of microbrewed beer samples) and B. cereus (detected in all FABs) were present in some products. B. cereus was detected most frequently in microbrewed beer (54.8% of samples) and nonpasteurized yakju (50.0%), followed by pasteurized yakju (28.8%), refined rice wine (25.0%), other fruit wines (12.3%), grape wine (8.6%), draft beer (5.6%), and pasteurized beer (2.2%) (P < 0.05). The finding that spore-forming B. cereus and coliform bacteria can survive the harsh conditions present in alcoholic beverages should be taken into account (alongside traditional quality indicators such as the presence of lactic acid-producing bacteria, acetic acid-producing bacteria, or both) when developing manufacturing systems and methods to prolong the shelf life of high-quality FAB products. New strategic quality management plans for various FABs are needed. more...

Background Removal of the plate following Le Fort I osteotomy and BSSO (bilateral sagittal split osteotomy) is a common procedure. However, patients who undergo plate removal experience intense pain and discomfort. This study investigated the half-maximal effective concentration (Ce50 ) of remifentanil in the prevention of plate removal pain under sedation using dexmedetomidine. Methods The study evaluated 18 patients, between 18 and 35 years of age, scheduled for elective surgery. Remifentanil infusion was initiated after sedation using dexmedetomidine, and started at a dose of 1.5 ng/mL on the first patient via target-controlled infusion (TCI). Patients received a loading dose of 1.0 µg/kg dexmedetomidine over 10 min, followed by a maintenance dose of 0.7 µg/kg/h. When the surgeon removed the plate, the patient Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score was observed. Results The Ce of remifentanil ranged from 0.9 to 2.1 ng/mL for the patients evaluated. The estimated effect-site concentrations of remifentanil associated with a 50% and 95% probability of reaching MOAA/S score of 3 were 1.28 and 2.51 ng/mL, respectively. Conclusions Plate removal of maxilla can be successfully performed without any pain or adverse effects by using the optimal remifentanil effect-site concentration (Ce50 , 1.28 ng/mL; Ce95 , 2.51 ng/mL) combined with sedation using dexmedetomidine. more...

The development of boceprevir and telaprevir was a major step forward in the treatment of chronic hepatitis C. In addition, the treatment of these infections has been recently revolutionized by the approval of sofosbuvir and simeprevir. However, there are several challenges associated with the application of novel drugs, such as new and more frequent adverse events, new drug interactions, and excessively high treatment costs. An additional concern is viral resistance. These considerations highlight the fact that direct-acting antiviral agents are not a panacea and may not be the best option for all patients who are in need of therapy. This retrospective study revealed that the sustained virologic response was not significantly reduced following peginterferon and ribavirin retreatment compared with the new therapy. We suggest that patients who experience relapse shortly after completing treatment with peginterferon and ribavirin have a reasonable chance of achieving a sustained virologic response when retreated with these drugs alone. more...

Missense mutations in the TP53 gene resulting in the accumulation of mutant proteins are extremely common in advanced ovarian cancer, which is characterised by peritoneal metastasis. Attachment of cancer cells to the peritoneal mesothelium is regarded as an initial, key step for the metastatic spread of ovarian cancer. In the present study, we investigated the possible role of a p53 mutant in the mesothelial adhesion of ovarian cancer cells. We found that OVCAR-3 cells with the R248 TP53 mutation (p53R248) were more adhesive to mesothelial Met5A cells than were A2780 cells expressing wild-type p53. In addition, ectopic expression of p53R248 in p53-null SKOV-3 cells significantly increased adhesion to Met5A cells. Knockdown of mutant p53 significantly compromised p53R248-induced cell adhesion to Met5A cells. Microarray analysis revealed that several adhesion-related genes, including integrin β4, were markedly up-regulated and certain signalling pathways, including PI3K/Akt, were activated in p53R248 transfectants of SKOV-3 cells. Inhibition of integrin β4 and Akt signalling using blocking antibody and the inhibitor LY294002, respectively, significantly attenuated p53R248-mediated ovarian cancer-mesothelial adhesion. These data suggest that the p53R248 mutant endows ovarian cancer cells with increased adhesiveness and that integrin β4 and Akt signalling are associated with the mutation-enhanced ovarian cancer-mesothelial cell adhesion. more...

Cyperus rotundus (Cyperaceae) has been widely used in traditional medicine for the treatment of various diseases, including cancer. Although an anti-tumour effect has been suggested for C. rotundus, the anti-tumour effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The n-hexane fraction of an ethanol extract of C. rotundus rhizomes was found to inhibit cell growth in ovarian cancer (A2780, SKOV3 and OVCAR3) and endometrial cancer (Hec1A and Ishikawa) cells. Among the thirteen sesquiterpenes isolated from the n-hexane fraction, some patchoulane-type compounds, but not eudesmane-type compounds, showed moderate cytotoxic activity in human ovarian cancer cells. In particular, the patchoulane sesquiterpene 6-acetoxy cyperene had the most potent cytotoxicity. In this regard, propidium iodide/Annexin V staining and terminal deoxynucleotidyl transferase dUTP (deoxynucleotide triphosphate) nick end labeling assay were performed to study cell cycle progression and apoptosis. 6-acetoxy cyperene induced apoptosis, as shown by the accumulation of sub-G1 and apoptotic cells. Furthermore, treatment with 6-acetoxy cyperene stimulated the activation of caspase-3, caspase-8 and caspase-9 and poly(ADP-ribose)polymerase in a dose-dependent manner. Pretreatment with caspase inhibitors neutralized the pro-apoptotic activity of 6-acetoxy cyperene. Taken together, these data suggest that 6-acetoxy cyperene, a patchoulane-type sesquiterpene isolated from C. rotundus rhizomes, is an anti-tumour compound that causes caspase-dependent apoptosis in ovarian cancer cells. Copyright © 2015 John WileySons, Ltd. more...

Eclipta prostrate L. (syn. E. alba Hassk), commonly known as False Daisy, has been used in traditional medicine in Asia to treat a variety of diseases, including cancer. Although an anti-tumor effect has been suggested for E. prostrata, the exact anti-tumor effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The aim of this study was to identify compounds with anti-cancer activity from E. prostrata and to investigate their mechanism of action.To assess cell viability, cell cycle progression, and apoptosis, we performed MTT assays and FACS analysis using Annexin and PI staining. We also investigated reactive oxygen species (ROS) production and caspase activation using flow cytometry and Western blot analysis, respectively. Cytosolic translocation of cytochrome c was measured using an ELISA kit. Antioxidants, MAPK signaling inhibitors, NADPH oxidase inhibitors, and siRNA were used to elucidate the molecular mechanism of action of the compound.We isolated five terthiophenes from the n-hexane fraction of E. prostrata; of these, α-terthienylmethanol possessed potent cytotoxic activity against human endometrial cancer cells (Hec1A and Ishikawa) (IC501μM). The growth inhibitory effect of α-terthienylmethanol was mediated by the induction of apoptosis, as shown by the accumulation of sub-G1 and apoptotic cells. In addition, α-terthienylmethanol triggered caspase activation and cytochrome c release into the cytosol in a time-dependent manner. Moreover, α-terthienylmethanol increased the intracellular level of ROS and decreased that of GSH, and the antioxidants N-acetyl-l-cysteine and catalase significantly attenuated α-terthienylmethanol-induced apoptosis. We further demonstrated that inhibition of the NADPH oxidase attenuated α-terthienylmethanol-induced cell death and ROS accumulation in endometrial cancer cells.Overall, these results suggest that α-terthienylmethanol, a naturally occurring terthiophene isolated from E. prostrata, induces apoptosis in human endometrial cancer cells by ROS production, partially via NADPH oxidase. more...

Objective The clinical application of cisplatin is limited due to its drug resistance and side effects. We investigated the effect of a phlorotannin-rich extract from the edible brown alga Ecklonia cava (PREC) and its major phlorotannin (dieckol) on cisplatin responsiveness and side effects. Methods The A2780 and SKOV3 ovarian cancer cell lines and the SKOV3-bearing mouse model were used. The MTT assay was applied to assess cell viability, and the annexin V assay was employed for apoptosis analysis. Reactive oxygen species (ROS) production and protein expression were assessed by H 2 DCFDA staining and Western blotting, respectively. Results We found that PREC enhanced the tumor growth-inhibitory effect of cisplatin and diminished cisplatin-induced nephrotoxicity and weight loss in SKOV3-bearing mice. PREC augmented cisplatin-induced apoptosis by activating caspases in SKOV3 and A2780 ovarian cancer cells. In addition, a combination of PREC and cisplatin-induced ovarian cancer cell apoptosis by downregulating the Akt and NFκB pathways. We further demonstrated that PREC increased intracellular ROS and that antioxidants significantly attenuated Akt-NFκB activation and apoptosis in ovarian cancer cells. In contrast, PREC inhibited cisplatin-induced ROS production and cell death in normal HEK293 kidney cells. Dieckol, a major compound in PREC, significantly enhanced the inhibition of tumor growth by cisplatin with less weight loss and kidney damage in a mouse model. Conclusion These data suggest that brown algae phlorotannins may improve the efficacy of platinum drugs for ovarian cancer by enhancing cancer cell apoptosis via the ROS/Akt/NFκB pathway and reduce nephrotoxicity by protecting against normal kidney cell damage. more...

Jaceosidin, a flavonoid derived from Artemisia princeps (Japanese mugwort), has been shown to inhibit the growth of several human cancer cells, However, the exact mechanism for the cytotoxic effect of jaceosidin is not completely understood. In this study, we investigated the molecular mechanism involved in the antiproliferative effect of jaceosidin in human endometrial cancer cells. We demonstrated that jaceosidin is a more potent inhibitor of cell growth than cisplatin in human endometrial cancer cells. In contrast, jaceosidin-induced cytotoxicity in normal endometrial cells was lower than that observed for cisplatin. Jaceosidin induced G2/M phase cell cycle arrest and modulated the levels of cyclin B and p-Cdc2 in Hec1A cells. Knockdown of p21 using specific siRNAs partially abrogated jaceosidin-induced cell growth inhibition. Additional mechanistic studies revealed that jaceosidin treatment resulted in an increase in phosphorylation of Cdc25C and ATM-Chk1/2. Ku55933, an ATM inhibitor, reversed jaceosidin-induced cell growth inhibition, in part. Moreover, jaceosidin treatment resulted in phosphorylation of ERK, and pretreatment with the ERK inhibitor, PD98059, attenuated cell growth inhibition by jaceosidin. These data suggest that jaceosidin, isolated from Japanese mugwort, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the Cdc2-cyclin B1 complex, followed by G2/M cell cycle arrest in endometrial cancer cells. more...

Ethnopharmacological relevance Artemisia leaves have long been used for the treatment of gynecological disorders, including infertility and dysmenorrhea, which can be commonly caused by endometriosis. In the present study, we investigated the effect of Artemisia princeps extract (APE) on the cell growth and apoptosis of human endometriotic cells. Materials and methods MTT assays and FACS analysis using PI and Annexin staining were performed to study cell viability, cell cycle progression, and apoptosis. We also explored the mechanism of APE-induced effects by evaluating the activation of caspases, Akt, p38, and NFκB. The expressions of XIAP, Bcl-2, and Bcl-xL were measured by real-time RT-PCR and Western blot analyses. Results APE significantly inhibited the cell viability of 11Z and 12Z human endometriotic epithelial cells. Interestingly, endometriotic cells were more sensitive to APE treatment than immortalized endometrial cells (HES). Treatment with APE induced apoptosis of 11Z cells in a time-dependent manner, as shown by accumulation of sub G1 and apoptotic cell populations. In addition, treatment with APE stimulated the activation of caspase -3, -8, and -9 in a dose- and time-dependent manner. Furthermore, p38 was activated by APE treatment, and the p38 inhibitor SB203580 markedly inhibited APE-induced cell death in 11Z cells. Moreover, treatment with APE suppressed the activation of NFκB and the expressions of anti-apoptotic factors such as XIAP, Bcl-2, and Bcl-xL. Conclusion These results indicate that APE is a potential anti-endometriotic agent, acting to induce apoptosis of endometrial cells through the modulation of the p38 and NFκB pathways. more...

A 29-year-old man suffering from dyspnea and eosinophilic pleural effusion after being on warfarin for pulmonary thromboembolism for a period of one month, was readmitted to our hospital. Etiology of pleural effusion other than warfarin was excluded. To the best of our knowledge, this is the first case of warfarin-induced pleural effusion reported in Korea. more...

Resistance to quinolones in Gram-negative bacteria is usually mediated by the following: (i) chromosomal mutations that alter the target enzymes, DNA gyrase and topoisomerase IV, in their quinolone resistance-determining regions (QRDR), (ii) changes in drug entry (loss of porin channels), and (iii) the presence of plasmid-mediated quinolone resistance (PMQR) determinants [qnrA, qnrB, qnrS, qnrC, and qnrD, coding for Qnr proteins that protect DNA gyrase from quinolone attack; aac(6′)-Ib-cr, coding for a protein that acetylates quinolones; and qepA, coding for a quinolone efflux pump] (2, 12). The recent worldwide emergence of PMQR due to the qnr and aac(6′)-Ib-cr genes is a concerning fact among human and animal Gram-negative pathogens (8). The aim of this study was to determine the prevalence of qnr genes among 93 consecutive nonrepetitive Enterobacteriaceae of animal origin and to characterize positive isolates. These isolates were collected from chickens (n = 37) and pigs (n = 56) at five farms near the city of Seoul (South Korea) in 2007. The presence of PMQR determinants and QRDR mutations was investigated by PCR-based detection and sequencing (2, 5, 6). The qnrA, qnrS, qnrC, qnrD, aac(6′)-Ib-cr, and qepA genes were not found. Two isolates (2.2%) were found to carry qnr-like genes (Citrobacter werkmanii PS012 and Citrobacter freundii S008). Sequence analysis identified two novel qnrB variants, qnrB22 and qnrB23, in C. werkmanii PS012 (isolated from a pig at the Daeyoung Farm) and C. freundii S008 (isolated from a chicken at the Hanmi Farm), respectively. These new variants were assigned according to the qnr numbering scheme shown in the Lahey website (http://www.lahey.org/qnrStudies). The qnrB22 gene had 99.7% nucleotide identity with qnrB4. The qnrB23 gene had 99.9% nucleotide identity with qnrB9. The deduced QnrB22 product had two amino acid substitutions (Ser36Cys and Gly188Val) compared with the amino acid sequence of QnrB4. Compared with the amino acid sequence of QnrB9, QnrB23 showed one amino acid substitution (Asn27Tyr). C. werkmanii PS012 showed a reduced susceptibility (MIC > 0.125 μg/ml) to fluoroquinolones (ofloxacin, norfloxacin, levofloxacin, and ciprofloxacin) (Table ​(Table1).1). C. freundii S008 was nonsusceptible (resistant or intermediate) to the fluoroquinolones (Table ​(Table1).1). The MICs were determined by E-test (AB Biodisk, Solna, Sweden) and interpreted according to Clinical and Laboratory Standards Institute guidelines (4). The QRDR mutations associated with fluoroquinolone resistance were not detected in the two isolates (Table ​(Table11). TABLE 1. Characteristics of the two Citrobacter isolates, their transconjugants, Escherichia coli DH5α transformants, and reference (recipient or host) strains The transfer of qnrB22- and qnrB23-harboring plasmids to Escherichia coli J53 AzideR was accomplished through mating experiments described previously (9). Transconjugants were selected on Mueller-Hinton agar plates containing sodium azide (150 μg/ml) and ciprofloxacin (0.125 μg/ml). Fluoroquinolone (or nalidixic acid) MICs of the two transconjugants (TrcPS012 and TrcS008) were similar to those of the donor strains (Table ​(Table1).1). Strain TrcS008, carrying qnrB23, had MIC values for nalidixic acid and fluoroquinolones that were higher than those of TrcPS012, harboring qnrB22 (Table ​(Table11). The PCR amplicons of the qnrB22 and qnrB23 genes were cloned into the vector pCR-BluntII-TOPO and transformed into the E. coli DH5α host strain (Invitrogen, Karlsruhe, Germany). Primers used were as follows: for cloning of qnrB22, 5′-ATGACTCTGGCGTTAGTTGG-3′ and 5′-TTAACCCATGACAGCGATACCAA-3′; and for cloning of qnrB23, 5′-ATGACGCCATTACTGTATAAAAAAACA-3′ and 5′-CTAGCCAATAATCGCGATGCC-3′. A decrease in quinolone susceptibility was observed with both transformants, even though the qnrB23-carrying transformant showed higher MICs than that carrying qnrB22 (Table ​(Table1).1). Fluoroquinolone (or nalidixic acid) MICs of two transformants (TrfPS012 and TrfS008) were lower than those of two transconjugants (TrcPS012 and TrcS008), which was compatible with a recent finding (11). The differences observed between transconjugants and transformants might be related to recipient susceptibility (E. coli DH5α was more susceptible than E. coli J53 AzideR), plasmid copy number, and/or the presence of additional PMQR determinants in the two plasmids. The conjugative plasmids of C. werkmanii PS012 and C. freundii S008 showed identical patterns (showing 13 distinct bands) and similar molecular sizes (about 23 kb) in restriction fragment length polymorphism analysis after digestion with BglII, as described previously (1). qnrB22- and qnrB23-harboring plasmids belonged to an incompatibility group, IncL/M, according to a PCR-based replicon-typing scheme (3). These results suggest that conjugative IncL/M plasmids might play a role in the dissemination and evolution of qnrB genes. The association of various antibiotic resistance genes, including PMQR determinants with conjugative IncL/M plasmids from human isolates of the Enterobacteriaceae, has been described in several reports (7, 10, 13, 14). Despite the currently low prevalence (2.2%) of qnrB22 and qnrB23, surveillance for bacterial isolates carrying these resistance determinants in animals is warranted. more...

Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram. more...

Missense-mutations of TP53 resulting in accumulation of mutant proteins are very frequent in human cancer including ovarian cancer. Aggressive ovarian cancer is characterized by a peritoneal metastasis which involves the adhesion, migration, and invasion of tumor cells to the peritoneal cavity. In the present study, we investigated the effect of p53 GOF mutation (p53R248) on the metastatic potential of human ovarian cancer cells. We found that forced overexpression of p53R248 significantly increased adhesion to mesothelial cell Met5A, migration, and invasion in p53-null SKOV-3 cells. Conversely, knockdown of mutant p53 using siRNA significantly compromised p53R248-induced cell adhesion, migration, and invasion. Microarray analysis revealed that several metastasis-related genes including integrins and S1PR1(Sphingosine-1-phosphate receptor 1), and certain signaling pathway including PI3K/AKT were markedly up-regulated in p53R248 transfectant SKOV-3R248 cells. Inhibition of PI3K/Akt signaling using specific inhibitor significantly attenuated p53R248-mediated mesothelial cell adhesion, migration, and invasion. These finding show for the first time that mutant p53R248 may exert gain-of-function activity to regulate metastasis-related gene expression and the PI3K/Akt singling pathway in ovarian cancer. Citation Format: Ji-Hye Ahn, Jong-Gyu Lee, Jung-Hye Choi. Mutant p53 enhances the metastatic potential of ovarian cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-84. doi:10.1158/1538-7445.AM2014-LB-84 more...

Cardiovascular manifestations in hyperthyroidism occur frequently with various phenotypes. An association between hyperthyroidism and pulmonary arterial hypertension has been reported. In previously reported cases, the hemodynamic and symptomatic recovery of pulmonary arterial hypertension is usually concomitant with achievement of euthyroidism. We report a patient who had pulmonary arterial hypertension associated with Graves' disease, which persisted after euthyroidism was obtained. more...