bluuebunny/crossref_metadata_2025 huggingface dataset:
Secure Localization in Wireless Sensor Networks with Mobile Beacons
Authors: Zhang Ting , He Jingsha , Yu Hong
Published: October 2012

We present a scheme, called SLMB, for secure sensor localization in WSNs in which we propose to use a mobile beacon node with the goal of reducing the overall energy consumption in sensor nodes during sensor localization. In the SLMB scheme, a mobile beacon node traverses through the network, collects information from unknown sensor nodes, figures out position relationship with these nodes, and sends the information to the base station where analysis and location calculation is carried out to relieve unknown sensor nodes from energy-consuming computation. The proposed SLMB scheme is also designed to resist wormhole attacks, and localization is developed based on a mathematical model to design a path for the mobile beacon node to traverse in order to cover the entire sensor network. To evaluate our scheme, we have performed simulations to demonstrate that the SLMB scheme can improve the success rate and the accuracy of sensor localization compared to other sensor localization schemes in hostile environments. Our simulation results also show that the SLMB scheme consumes much less energy than traditional distributed sensor localization schemes, which is an important metric in measuring the effectiveness and usefulness of any schemes targeted for applications in WSNs.
A New Calculation for Boolean Derivative Using Cheng Product
Authors: Chen Hao , Sun Jitao
Published: October 2012

The matrix expression and relationships among several definitions of Boolean derivatives are given by using the Cheng product. We introduce several definitions of Boolean derivatives. By using the Cheng product, the matrix expressions of Boolean derivative are given, respectively. Furthermore, the relationships among different definitions are presented. The logical calculation is converted into matrix product. This helps to extend the application of Boolean derivative. At last, an example is given to illustrate the main results.
Quasimonotone and Almost Increasing Sequences and Their New Applications
Authors: Bor Hüseyin
Published: October 2012

Recently, we have proved a main theorem dealing with the absolute Nörlund summability factors of infinite series by using δ‐quasimonotone sequences. In this paper, we prove that result under weaker conditions. A new result has also been obtained.
Market-Based Approach to Mobile Surveillance Systems
Authors: Elmogy Ahmed M. , Khamis Alaa M. , Karray Fakhri O.
Published: October 2012

The active surveillance of public and private sites is increasingly becoming a very important and critical issue. It is, therefore, imperative to develop mobile surveillance systems to protect these sites. Modern surveillance systems encompass spatially distributed mobile and static sensors in order to provide effective monitoring of persistent and transient objects and events in a given area of interest (AOI). The realization of the potential of mobile surveillance requires the solution of different challenging problems such as task allocation, mobile sensor deployment, multisensor management, cooperative object detection and tracking, decentralized data fusion, and interoperability and accessibility of system nodes. This paper proposes a market-based approach that can be used to handle different problems of mobile surveillance systems. Task allocation and cooperative target tracking are studied using the proposed approach as two challenging problems of mobile surveillance systems. These challenges are addressed individually and collectively.
On Variational Inclusion and Common Fixed Point Problems in q‐Uniformly Smooth Banach Spaces
Authors: Song Yanlai , Hu Huiying , Ceng Luchuan
Published: October 2012

We introduce a general iterative algorithm for finding a common element of the common fixed‐point set of an infinite family of λi‐strict pseudocontractions and the solution set of a general system of variational inclusions for two inverse strongly accretive operators in a q‐uniformly smooth Banach space. Then, we prove a strong convergence theorem for the iterative sequence generated by the proposed iterative algorithm under very mild conditions. The methods in the paper are novel and different from those in the early and recent literature. Our results can be viewed as the improvement, supplementation, development, and extension of the corresponding results in some references to a great extent.
Generalized Proximal ψ‐Contraction Mappings and Best Proximity Points
Authors: Sanhan Winate , Mongkolkeha Chirasak , Kumam Poom
Published: October 2012

We generalized the notion of proximal contractions of the
first and the second kinds and established the best proximity point theorems for
these classes. Our results improve and extend recent result of Sadiq Basha (2011) and some authors.
The Long-Term Effects of Mandibular Distraction Osteogenesis on Developing Deciduous Molar Teeth
Authors: Hong Paul , Graham Elise , Belyea James , Taylor S. Mark , Kearns Donald B. , Bezuhly Michael
Published: October 2012

Background.Many studies have demonstrated the effectiveness of mandibular distraction osteogenesis (MDO) in alleviating the micrognathia-associated upper airway obstruction but very few studies have focused on long-term dental outcomes.Objective.To report the effect of MDO on developing deciduous molars in the distraction area.Methods.A retrospective chart review was performed to identify patients with Pierre Robin sequence who underwent MDO with documented long-term dental assessments.Results.Ten children (mean age at surgery 69.8 days; 6 boys and 4 girls) were included for analysis. All patients underwent bilateral MDO with an inverted L-shaped osteotomy to avoid injuring tooth buds. The dental developmental stage was primary dentition in all children. Overall, 3 patients developed minor dental problems involving 4 molar teeth (2 root malformations and 2 shape anomalies) but they did not require any interventions.Conclusion.Significant primary molar developmental complications were not seen in our patients. The use of internal distractor device with an inverted L-shaped osteotomy seems to be a safe surgical approach in regards to dental outcomes.
Protein Oxidative Damage at the Crossroads of Cellular Senescence, Aging, and Age-Related Diseases
Authors: Baraibar Martin A. , Liu Liang , Ahmed Emad K. , Friguet Bertrand
Published: October 2012

Protein damage mediated by oxidation, protein adducts formation with advanced glycated end products and with products of lipid peroxidation, has been implicated during aging and age-related diseases, such as neurodegenerative diseases. Increased protein modification has also been described upon replicative senescence of human fibroblasts, a valid model for studying agingin vitro. However, the mechanisms by which these modified proteins could impact on the development of the senescent phenotype and the pathogenesis of age-related diseases remain elusive. In this study, we performedin silicoapproaches to evidence molecular actors and cellular pathways affected by these damaged proteins. A database of proteins modified by carbonylation, glycation, and lipid peroxidation products during aging and age-related diseases was built and compared to those proteins identified during cellular replicative senescencein vitro. Common cellular pathways evidenced by enzymes involved in intermediate metabolism were found to be targeted by these modifications, although different tissues have been examined. These results underscore the potential effect of protein modification in the impairment of cellular metabolism during aging and age-related diseases.
Slow Cortical Potentials and Amplification—Part I: N1-P2 Measures
Authors: Marynewich Susan , Jenstad Lorienne M. , Stapells David R.
Published: October 2012

Slow cortical potentials (SCPs) are currently of great interest in the hearing aid fitting process for infants; however, there is conflicting evidence in the literature concerning the use of SCPs for this purpose. The current study investigated SCP amplitudes and latencies in young normal-hearing listeners in response to a 60 ms duration tonal stimulus (1000 Hz) presented at three intensities (30, 50, and 70 dB SPL) in aided and unaided conditions using three hearing aids (Analog, DigitalA, and DigitalB) with two gain settings (20 and 40 dB). Results showed that SCP amplitudes were smaller for the digital hearing aids compared with the analog hearing aid, and none of the hearing aids resulted in a reliable increase in response amplitude relative to the unaided across conditions. SCP latencies in analog conditions were not significantly different from latencies in the unaided conditions; however, both digital hearing aids resulted in significantly delayed SCP latencies. The results of the current study (as well as several previous studies) indicate that the SCP may not accurately reflect the amplified stimulus expected from the prescribed hearing aids. Thus, “aided-SCP” results must be interpreted with caution, and more research is required concerning possible clinical use of this technique.
Acute Ulnar Shortening for Delayed Presentation of Distal Radius Growth Arrest in an Adolescent
Authors: Ellanti Prasad , Harrington Paul
Published: October 2012

Distal radius physeal fractures are common in children and adolescents. However, posttraumatic growth arrest is uncommon. The management of posttraumatic growth arrest is dependent on the severity of the deformity and the remaining growth potential of the patient. Various treatment options exist. We present a 17-year-old male with distal radius growth arrest who presented four years after the initial injury. He had a symptomatic 15 mm positive ulnar variance managed with an ulnar shortening osteotomy with the use of the AO mini distractor intraoperatively. To the best of our knowledge, an acute ulnar shortening of 15 mm is the largest reported.
L∞ Control with Finite‐Time Stability for Switched Systems under Asynchronous Switching
Authors: Wang Ronghao , Xing Jianchun , Wang Ping , Yang Qiliang , Xiang Zhengrong
Published: October 2012

This paper is concerned with the problem of controller design for switched systems under asynchronous switching with exogenous disturbances. The attention is focused on designing the feedback controller that guarantees the finite‐time bounded and L∞ finite‐time stability of the dynamic system. Firstly, when there exists asynchronous switching between the controller and the system, a sufficient condition for the existence of stabilizing switching law for the addressed switched system is derived. It is proved that the switched system is finite‐time stabilizable under asynchronous switching satisfying the average dwell‐time condition. Furthermore, the problem of L∞ control for switched systems under asynchronous switching is also investigated. Finally, a numerical example is given to illustrate the effectiveness of the proposed method.
Long-Term Deformation Monitoring of Metro-Tunnel Airshaft Excavation during Construction Stage
Authors: Ran L. , Yi T. H. , Ye X. W. , Dong X. B.
Published: October 2012

The project of Hangzhou Metro Line 1 is the first metro line of the urban rapid rail transit system in Hangzhou, China, which is one of the largest municipal projects of Hangzhou and is being constructed commencing from March 28, 2007 and expected to be completed by October 1, 2012. This metro line has a total length of 48 km and 34 stations, connecting Hangzhou downtown with the suburban area of the city. Owing to the complex geological condition, harsh construction situation, and immature computational methodology, construction of metro systems is often subjected to considerable sources of uncertainties. To ensure the safety of the adjacent building structures, it is a vital necessity to monitor deep excavations of metro tunnels at their in-construction stage. This paper introduces the instrumentation system for settlement monitoring of a metro-tunnel airshaft of the project of Hangzhou Metro Line 1 during the construction of deep excavation. The long-term settlement data monitored by the measurement markers installed at the surface ground and in the depth direction of the airshaft excavation construction site are analyzed and presented in detail. The obtained results indicate that the settlements at the instrumented locations of the construction site during different construction steps vary steadily in an allowable variation range.
Reconstruction of Sugar Metabolic Pathways of Giardia lamblia
Authors: Han Jian , Collins Lesley J.
Published: October 2012

Giardia lamblia is an “important” pathogen of humans, but as a diplomonad excavate it is evolutionarily distant from other eukaryotes and relatively little is known about its core metabolic pathways. KEGG, the widely referenced site for providing information of metabolism, does not yet include many enzymes from Giardia species. Here we identify Giardia’s core sugar metabolism using standard bioinformatic approaches. By comparing Giardia proteomes with known enzymes from other species, we have identified enzymes in the glycolysis pathway, as well as some enzymes involved in the TCA cycle and oxidative phosphorylation. However, the majority of enzymes from the latter two pathways were not identifiable, indicating the likely absence of these functionalities. We have also found enzymes from the Giardia glycolysis pathway that appear more similar to those from bacteria. Because these enzymes are different from those found in mammals, the host organisms for Giardia, we raise the possibility that these bacteria-like enzymes could be novel drug targets for treating Giardia infections.
Synthesis and Evaluation of Some New Thiazolidin‐4‐One Derivatives as Potential Antimicrobial Agents
Authors: Baviskar B. A. , Khadabadi S. S. , Deore S. L.
Published: October 2012

A new series of N‐{4‐methyl‐5‐[4‐(4‐oxo‐2‐phenyl(1,3‐thiazolidin‐3‐yl)]‐5‐sulfanyl(1,2,4‐triazol‐3‐yl)‐1,3‐thiazol‐2‐yl }acetamide (7a‐l) was synthesized in order to determine their antimicrobial activity and feasible structure–activity relationships. The compounds were synthesized in good yield and the structures of all newly synthesized compounds were established on the basis of their IR, 1HNMR, and elemental analysis. The synthesized compounds were tested in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi and antifungal activity against Aspergillus niger, Candida albicans by measuring the zone of inhibition in mm.
Extraction and Transport of Amino Acids Using Kryptofix 5 as Carrier through Liquid Membrane
Authors: Raizada Pankaj , Sharma Uma
Published: October 2012

The present work explores membrane‐mediated extraction and transport studies of amino acids through artificial bulk liquid membrane system with kryptofix 5 as a carrier. The various reaction parameters such as amino acid concentration, carrier concentration, time, pH, and stirring effect were studied to optimize reaction conditions. The stirring of source and receiving phases increased the efficiency of extraction process. Noncyclic receptor kryptofix 5 with five oxyethylene units and terminal aromatic donor end groups governs its transport and extraction efficiency. The extraction and transport efficiency followed the following trend: valine > alanine > glycine > threonine. Supported liquid membrane (SLM) studies were performed using cellulose nitrate, PTFE, eggshell, and onion membranes. The egg shell membrane support proved to be most efficient due to intricate network of water insoluble proteins fibers with very high surface area and homogeneity.
The PI3K/AKT/mTOR Pathway as a Therapeutic Target in Endometrial Cancer
Authors: Slomovitz Brian M. , Coleman Robert L.
Published: October 2012

Endometrial cancer is the most common gynecologic malignancy in the United States. Overactivation of the PI3K/AKT/mTOR pathway, a signaling pathway that plays an important role in cellular growth and survival, has recently been implicated in endometrial cancer pathogenesis, and as such, inhibition of the PI3K/AKT/mTOR pathway is of therapeutic interest. Preclinical and clinical studies are proving useful in elucidating the antitumor effects of different PI3K/AKT/mTOR pathway inhibitors, and in defining which patient populations these inhibitors might be most effective in. For example, an increasing amount of preclinical data suggest that loss of PTEN or genetic alteration of PIK3CA may be indicators of sensitivity to PI3K/AKT/mTOR pathway inhibition, while activating KRAS mutations may predict resistance. In the latter case, combined inhibition of the RAS/RAF/MEK and PI3K/AKT/mTOR pathways has been suggested as a therapeutic strategy. In addition, the PI3K/AKT/mTOR pathway has been implicated in conferring resistance to conventional therapies, and so PI3K/AKT/mTOR pathway inhibitors in combination with hormonal and/or cytotoxic agents are being evaluated. In conclusion, preclinical models are providing insights into the antitumor activity of PI3K/AKT/mTOR pathway inhibition, and are helping define patient populations most likely to benefit from these therapies. Clinical validation of these findings is ongoing. Clin Cancer Res; 18(21); 5856–64. ©2012 AACR.
Ethacrynic Acid and a Derivative Enhance Apoptosis in Arsenic Trioxide–Treated Myeloid Leukemia and Lymphoma Cells: The Role of Glutathione S-Transferase P1-1
Authors: Wang Rui , Liu Changda , Xia Lijuan , Zhao Guisen , Gabrilove Janice , Waxman Samuel , Jing Yongkui
Published: October 2012

Purpose: Arsenic trioxide (ATO) as a single agent is used for treatment of acute promyelocytic leukemia (APL) with minimal toxicity, but therapeutic effect of ATO in other types of malignancies has not been achieved. We tested whether a combination with ethacrynic acid (EA), a glutathione S-transferase P1-1 (GSTP1-1) inhibitor, and a reactive oxygen species (ROS) inducer will extend the therapeutic effect of ATO beyond APL.

Experimental Design: The combined apoptotic effects of ATO plus ethacrynic acid were tested in non-APL leukemia and lymphoma cell lines. The role of ROS, GSTP1-1, glutathione (GSH), and Mcl-1 in apoptosis was determined. The selective response to this combination of cells with and without GSTP1-1 expression was compared.

Results: ATO/EA combination synergistically induced apoptosis in myeloid leukemia and lymphoma cells. This treatment produced high ROS levels, activated c-jun-NH2-kinase (JNK), and reduced Mcl-1 protein. This led to the decrease of mitochondrial transmembrane potential, release of cytochrome c, and subsequently, to activation of caspase-3 and -9. Induction of apoptosis in leukemia and lymphoma cells expressing GSTP1-1 required high ethacrynic acid concentrations to be combined with ATO. Silencing of GSTP1 in leukemia cells sensitized them to ATO/EA–induced apoptosis. In a subgroup of B-cell lymphoma, which does not express GSTP1-1, lower concentrations of ethacrynic acid and its more potent derivative, ethacrynic acid butyl-ester (EABE), decreased intracellular GSH levels and synergistically induced apoptosis when combined with ATO.

Conclusion: B-cell lymphoma cells lacking GSTP1-1 are more sensitive than myeloid leukemia cells to ATO/EA–induced apoptosis. Clin Cancer Res; 18(24); 6690–701. ©2012 AACR.
Translating the Therapeutic Potential of AZD4547 in FGFR1-Amplified Non–Small Cell Lung Cancer through the Use of Patient-Derived Tumor Xenograft Models
Authors: Zhang Jingchuan , Zhang Lin , Su Xinying , Li Ming , Xie Liang , Malchers Florian , Fan ShuQiong , Yin XiaoLu , Xu YanPing , Liu Kunji , Dong Zhengwei , Zhu Guanshan , Qian Ziliang , Tang Lili , Zhan Ping , Ji Qunsheng , Kilgour Elaine , Smith Paul D. , Brooks A. Nigel , Thomas Roman K. , Gavine Paul R.
Published: October 2012

Purpose: To investigate the incidence of FGFR1 amplification in Chinese non–small cell lung cancer (NSCLC) and to preclinically test the hypothesis that the novel, potent, and selective fibroblast growth factor receptor (FGFR) small-molecule inhibitor AZD4547 will deliver potent antitumor activity in NSCLC FGFR1–amplified patient-derived tumor xenograft (PDTX) models.

Experimental Design: A range of assays was used to assess the translational relevance of FGFR1 amplification and AZD4547 treatment including in vitro lung cell line panel screening and pharmacodynamic (PD) analysis, FGFR1 FISH tissue microarray (TMA) analysis of Chinese NSCLC (n = 127), and, importantly, antitumor efficacy testing and PD analysis of lung PDTX models using AZD4547.

Results: The incidence of FGFR1 amplification within Chinese patient NSCLC tumors was 12.5% of squamous origin (6 of 48) and 7% of adenocarcinoma (5 of 76). AZD4547 displayed a highly selective profile across a lung cell line panel, potently inhibiting cell growth only in those lines harboring amplified FGFR1 (GI50 = 0.003–0.111 μmol/L). AZD4547 induced potent tumor stasis or regressive effects in four of five FGFR1-amplified squamous NSCLC PDTX models. Pharmacodynamic modulation was observed in vivo, and antitumor efficacy correlated well with FGFR1 FISH score and protein expression level.

Conclusions: This study provides novel epidemiologic data through identification of FGFR1 gene amplification in Chinese NSCLC specimens (particularly squamous) and, importantly, extends the clinical significance of this finding by using multiple FGFR1-amplified squamous lung cancer PDTX models to show tumor stasis or regression effects using a specific FGFR inhibitor (AZD4547). Thus, the translational science presented here provides a strong rationale for investigation of AZD4547 as a therapeutic option for patients with squamous NSCLC tumors harboring amplification of FGFR1. Clin Cancer Res; 18(24); 6658–67. ©2012 AACR.
Uterine Endometrial Carcinoma: 10 Years’ Experience with Long-Term Follow-Up at a Single Korean Institution
Authors: Lee Eun-Ju , Kim Tae-Joong , Choi Chel Hun , Lee Jeong-Won , Lee Je-Ho , Bae Duk-Soo , Park Hyoung Moo , Kim Byoung-Gie
Published: October 2012

Aim: To evaluate prognostic factors in Korean patients with endometrial cancer. Methods: A retrospective analysis was conducted on 248 patients who were staged surgically at the Samsung Medical Center between 1995 and 2004. Survival data were analyzed using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression method. Results: The median age was 51 years (range 21–75), which was younger than in previous studies in Western patients, and the age of 50 years was the cutoff to predict survival. More than half (55.6%) were normal weight or underweight (BMI <25). Multivariate analysis revealed that age, Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage, and histopathology were independent predictors of disease-free survival, and FIGO stage and p53 mutation were independent prognostic factors for disease-specific survival (DSS). The 5-year DSS for patients with stage I, II, III and IV disease was 95.6, 93.8, 69.8 and 50%, respectively. The 5-year DSS rate for patients with a p53 mutation was 84.4%, compared with 97.1% for patients without. Conclusions: Korean patients with endometrial cancer were younger and had a lower BMI than previously reported. Furthermore, age greater than 50 years was predictive of a poor outcome. Age, FIGO stage, histopathology and a p53 mutation were independent prognostic factors for survival.
Subpleural versus Deep Lung Biopsies Obtained during Pleuroscopy for Histological Examination: An Experimental Animal Study
Authors: Emam Raef H. , Froudarakis Marios E. , Refaat Ahmed I. , Akl Maha , Maldonado Fabien , Astoul Philippe
Published: October 2012

Background: Lung biopsies obtained during medical pleuroscopy using coagulating forceps could represent a cost-effective alternative to surgical lung biopsies in patients with diffuse parenchymal lung diseases (DPLD). However, it is not clear whether these patients should undergo deeplung biopsies rather than more superficial subpleural lung biopsies. Objectives: The aim of this experimental animal study was to compare gross and microscopic features of deep and subpleural pleuroscopic lung biopsy samples. Methods: Six male sheep (median weight 40 kg) underwent lung biopsies via pleuroscopy under general anesthesia. The following parameters were studied: weight, size, quality of the parenchyma and visceral pleura, parenchymal vessels and bronchial tissue. Results: The mean number of biopsies taken per animal was 4.5 ± 1.22 and 4.83 ± 1.33 (p = 0.36) for deep and subpleural biopsies, respectively. The mean size of deep and subpleural biopsies was 1.758 ± 0.478 and 1.283 ± 0.851 cm2, respectively (p = 0.0006). The mean weight of deep biopsies and subpleural biopsies was 0.156 ± 0.092 and 0.145 ± 0.047 mg, respectively (p = 0.83). No statistically significant difference was found between subpleural and deep biopsies regarding the mean quality scores of parenchyma-pleura (p = 0.36), vessels (p = 0.36), or bronchial tissue (p = 0.20). Conclusion: Both subpleural biopsies obtained during pleuroscopy and deep lung biopsy specimens obtained by electrocautery in animal subjects provided satisfactory material for histologic examination. Therefore, in DPLD, where the subpleural layers are involved, subpleural biopsies obtained during pleuroscopy might be sufficient for establishing an accurate diagnosis.
Risk Factors for Multiple Sclerosis in Kuwait: A Population-Based Case-Control Study
Authors: Al-Afasy Hanan H. , Al-Obaidan Mohammed A. , Al-Ansari Yousef A. , Al-Yatama Sarah A. , Al-Rukaibi Mohammed S. , Makki Nourah I. , Suresh Anita , Akhtar Saeed
Published: October 2012

Multiple sclerosis (MS) is a chronic and progressively disabling inflammatory autoimmune disorder of the central nervous system. MS has a multifactorial etiology and is triggered by environmental factors in individuals with complex genetic risk profiles. The epidemiology of MS changes with the spatial and temporal distribution of these genetic and nongenetic risk factors. This population-based matched case-control study aimed to determine the risk factors for MS in Kuwait. From May 2 to 9, 2010, we enrolled 101 confirmed MS cases using the list frame maintained by the Multiple Sclerosis Association of Kuwait. For each case, two population controls individually matched for age (±2 years), gender and nationality were selected. Data on demographic, socioeconomic variables, potential genetic and environmental factors were collected using a structured questionnaire. For a case, the questions were directed to the period that preceded the recognition of the disease, while for each of the two matched controls, a date of ‘pseudodiagnosis’ of MS was established, i.e. the date on which the control subject was of the same age as his/her matched case was at MS diagnosis and accordingly questions were directed to the preceding period. The multivariable conditional logistic regression model showed that compared with controls, the cases were significantly more likely to have a family history of MS [matched odds ratio (OR)adj = 6.7; 95% confidence interval (95% CI): 2.5–18.0; p < 0.001] or have suffered from a head trauma in the past before MS diagnosis (matched ORadj = 2.6; 95% CI: 1.2–5.5; p = 0.014). Furthermore, compared with controls, cases were significantly more likely to have stayed in Kuwait during the Iraqi invasion of 1990 (matched ORadj = 1.8; 95% CI: 1.1–3.5; p = 0.022). This study showed that a family history of MS, a history of head injury, and presence in Kuwait at the time of the Iraqi invasion of 1990 were associated with a significantly increased MS risk. Future retrospective cohort studies by using existing biological and epidemiological databases may provide a clue to MS etiology.
Inhibition of Histamine H1 Receptor Activity Modulates Proinflammatory Cytokine Production of Dendritic Cells through c-Rel Activity
Authors: Lee Chin-Lai , Hsu Shih-Hsien , Jong Yuh-Jyh , Hung Chih-Hsing , Suen Jau-Ling
Published: October 2012

Background: Histamine exerts diverse effects on immune regulation through four types of histamine receptors (HRs). Among them, type 1 receptor (H1R) plays an important role in allergic inflammation. Dendritic cells (DCs), which express at least three types of HRs, are professional antigen-presenting cells controlling the development of allergic inflammation. However, the molecular mechanisms involved in H1R-mediated NF-ĸB signaling of DCs remain poorly defined. Methods: Bone-marrow (BM)-derived DCs (BM-DCs) were treated with H1R inverse agonists to interrupt basal H1R-mediated signaling. The crosstalk of H1R-mediated signaling and the NF-ĸB pathway was examined by NF-ĸB cellular activity using a luciferase reporter assay, NF-ĸB subunit analysis using Western blotting and TNF-α promoter activity using chromatin immunoprecipitation. Results: Blockage of H1R signaling by inverse agonists significantly inhibited TNF-α and IL-6 production of BM-DCs. H1R-specific agonists were able to enhance TNF-α production, but this overexpression was significantly inhibited by NF-ĸB inhibitor. The H1R inverse agonist ketotifen also suppressed cellular NF-ĸB activity, suggesting crosstalk between H1R and NF-ĸB signaling in DCs. After comprehensive analysis of NF-ĸB subunits, c-Rel protein expression was significantly down-regulated in ketotifen-treated BM-DCs, which led to inhibition of the promoter activity of TNF-α. Finally, adoptive transfer of the ketotifen-treated BM-DCs did not induce significant allergic airway inflammation compared to that of control cells in vivo. Conclusions: Our results suggest that c-Rel controls H1R-mediated proinflammatory cytokine production in DCs. This study provides a potential mechanism of H1R-mediated signaling and NF-ĸB pathway crosstalk in allergic inflammation.
Association Study of Matrix Metalloproteinase-12 Gene Polymorphisms and Asthma in a Japanese Population
Authors: Yamaide Fumiya , Undarmaa Siizkhuu , Mashimo Yoichi , Shimojo Naoki , Arima Takayasu , Morita Yoshinori , Hirota Tomomitsu , Fujita Kimie , Miyatake Akihiko , Doi Satoru , Sato Kazuki , Suzuki Shuichi , Nishimuta Toshiyuki , Watanabe Hiroko , Hoshioka Akira , Tomiita Minako , Yamaide Akiko , Watanabe Misa , Okamoto Yoshitaka , Kohno Yoichi , Tamari Mayumi , Hata Akira , Suzuki Yoichi
Published: October 2012

Background: Matrix metalloproteinase 12 gene (MMP12) has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nucleotide polymorphisms (SNPs) of MMP12 are associated with a risk for asthma in a Japanese population. Methods: We tested for an association between SNPs in MMP12 and asthma, including its severity, in a Japanese population (630 pediatric and 417 adult patients with atopic asthma and 336 children and 632 adults as controls). The rs652438 A and G variants (N357S) were generated by site-directed mutagenesis and an assay with artificial peptide substrates was used to compare two types of MMP12 activity. The effect of MMP12 inhibition with MMP12-specific small interfering RNA (siRNA) on chemokine secretion from airway epithelial cells was also tested in vitro. Results: N357S showed a p value <0.05 for childhood and combined (adult plus childhood) asthma in the dominant model [odds ratio (OR) 1.60, 95% confidence interval (CI) 1.00–2.56, p = 0.047; OR 1.40, 95% CI 1.04–1.89, p = 0.028, respectively]. This risk variant is associated with asthma severity in adult patients. In the functional assay, the minor-allele enzyme showed significantly lower activity than the major-allele enzyme. MMP12-specific siRNA suppressed IP-10 secretion from airway epithelial cells upon stimulation with IFN-β. Conclusions: Our results suggest that MMP12 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue.
Investigation of Optimal Prostate Biopsy Schemes for Chinese Patients with Different Clinical Characteristics
Authors: Chen Ming-Kun , Luo Yun , Zhang Hao , Lu Ming-Hua , Pang Jun , Gao Xin
Published: October 2012

Purpose: To investigate the optimal schemes of prostate biopsy according to prostate volume (PV), age and transrectal ultrasound (TRUS) status in Chinese men. Methods: 923 consecutive patients who underwent initial TRUS-guided systematic 12-core prostate biopsy (12PBx) were enrolled in this study. The 12PBx was obtained by overlapping of conventional sextant, lateral base, mid-gland of peripheral zone and apex. Each sample was individually marked and inked before fixation. Patients were divided into 8 subgroups on the basis of independent risk factors investigated using logistic regression model. Subsequently, 12PBx was defined as self-control for the analysis of biopsy schemes (6-, 8- and 10PBx) on individual core basis. The prostate cancer detection rates (CDRs) of 6-, 8-, 10- and 12PBx were compared for each individual subgroup. Results: The 12PBx detected 253 (27.4%) cases of prostate cancer (PCa), of which 67.2, 47.1 and 61.3% were located in the base, mid-gland and apex, respectively. Multivariate analysis indicated that age, TRUS status and PV were independent risk factors for PCa detection. CDR increased with increasing biopsy cores. However, for patients with age ≥65 years, positive TRUS and PV <38.5 cm3, CDR of 8PBx (30.6%) was similar to 10PBx (32.2%) and 12PBx (32.2%); for patients with age ≥65 years, negative TRUS and PV <38.5 cm3 or ones with age ≥65 years, positive TRUS and PV ≥38.5 cm3, 10PBx was as effective as 12PBx in detecting PCa (27.8, 27.5 vs. 28.9, 29.3%, respectively). Conclusion: Age, TRUS status and PV were independent risk factors for PCa detection. Traditional sextant biopsy is not recommended. 8-, 10-, or 12PBx as an individual biopsy scheme might be adopted according to these risk factors for Chinese patients.
Design, Mechanism of Action, Bioavailability and Therapeutic Effects of Mn Porphyrin-Based Redox Modulators
Authors: Tovmasyan Artak , Sheng Huaxin , Weitner Tin , Arulpragasam Amanda , Lu Miaomiao , Warner David S. , Vujaskovic Zeljko , Spasojevic Ivan , Batinic-Haberle Ines
Published: October 2012

Based on aqueous redox chemistry and simple in vivo models of oxidative stress, Escherichia coli and Saccharomyces cerevisiae, the cationic Mn(III) N-substituted pyridylporphyrins (MnPs) have been identified as the most potent cellular redox modulators within the porphyrin class of drugs; their efficacy in animal models of diseases that have oxidative stress in common is based on their high ability to catalytically remove superoxide, peroxynitrite, carbonate anion radical, hypochlorite, nitric oxide, lipid peroxyl and alkoxyl radicals, thus suppressing the primary oxidative event. While doing so MnPs could couple with cellular reductants and redox-active proteins. Reactive species are widely accepted as regulators of cellular transcriptional activity: minute, nanomolar levels are essential for normal cell function, while submicromolar or micromolar levels impose oxidative stress, which is evidenced in increased inflammatory and immune responses. By removing reactive species, MnPs affect redox-based cellular transcriptional activity and consequently secondary oxidative stress, and in turn inflammatory processes. The equal ability to reduce and oxidize superoxide during the dismutation process and recently accumulated results suggest that pro-oxidative actions of MnPs may also contribute to their therapeutic effects. All our data identify the superoxide dismutase-like activity, estimated by log kcat(O2–), as a good measure for the therapeutic efficacy of MnPs. Their accumulation in mitochondria and their ability to cross the blood-brain barrier contribute to their remarkable efficacy. We summarize herein the therapeutic effects of MnPs in cancer, central nervous system injuries, diabetes, their radioprotective action and potential for imaging. Few of the most potent modulators of cellular redox-based pathways, MnTE2-PyP5+, MnTDE-2-ImP5+, MnTnHex-2-PyP5+ and MnTnBuOE-2-PyP5+, are under preclinical and clinical development.
Microvascular Dilatation after Haemodialysis Is Determined by the Volume of Fluid Removed and Fall in Mean Arterial Pressure
Authors: Tow Foong Kien Newk-Fon Hey , Ooi Qi Lun , Wong Tien Y. , Kawasaki Ryo , Colville Deb , Mount Peter , Savige Judy
Published: October 2012

Background/Aims: The effects of haemodialysis on the microcirculation are poorly understood. This study examined the changes in small vessel calibre. Methods: 24 patients (including 12 males, median age 62.5 years, range 30–87) underwent digital retinal photography immediately before and after routine haemodialysis. Arteriolar and venular calibres were measured from the images by a trained grader using a highly reproducible, computer-assisted method. Results: Patients had an average 2.0 ± 0.3 litres of fluid removed with dialysis, and their mean arterial blood pressure fell by 6.8 mm Hg (CI 13.8–0.2, p = 0.06). Retinal arteriole calibre did not change (mean difference 2.3 µm, CI –1.1 to 5.7, p = 0.17) but the venules dilated (mean difference 12.7 µm, CI 7.3–18.3, p < 0.001). Calibre returned to baseline by 2 h. Venules dilated less in diabetics than non-diabetics (mean difference –6.2 µm, CI –9.6 to –2.9, p < 0.01). Retinal venular dilatation correlated positively with the volume of fluid removed per kilogramme body weight (5.9, CI 0.2–11.5, p = 0.04), and negatively with the fall in mean arterial pressure (–0.36, CI –0.72 to –0.01, p < 0.05) after adjusting for age, gender, diabetes and dyslipidaemia. Conclusion: Haemodialysis is associated with systemic venular dilatation.
Association between Serotonin Transporter-Linked Polymorphic Region and Escitalopram Antidepressant Treatment Response in Korean Patients with Major Depressive Disorder
Authors: Won Eun-Soo , Chang Hun-Soo , Lee Hwa-Young , Ham Byung-Joo , Lee Min-Soo
Published: October 2012

Objective: Various studies have shown that short (s)/long (l) polymorphisms of the serotonin transporter-linked polymorphic region (5-HTTLPR) might predict treatment outcome to selective serotonin reuptake inhibitors. The purpose of this study was to evaluate the association between 5-HTTLPR and clinical response to escitalopram treatment in Korean subjects with major depressive disorder. Methods: One hundred and fifteen Korean patients diagnosed with major depressive disorder were evaluated during 8 weeks of escitalopram treatment at a dose of 5–20 mg/day. Patients were genotyped for 5-HTTLPR using polymerase chain reaction. Clinical symptoms were evaluated by the 21-item Hamilton Depression Rating (HAMD-21) scale during the 8 weeks of treatment. Results: Therapeutic response to antidepressant escitalopram was better in s allele carriers (ss, sl) than in l allele homozygotes (ll) at 8 weeks of treatment (OR = 6.24, p = 0.026). The proportion of s allele carriers in responders was higher than that in non-responders (96.6 vs. 85.7%). The percentile decline in HAMD-21 in s allele carriers (59.86 ± 3.23%) was larger than that in HAMD-21 in l allele homozygotes (43.13 ± 11.49%; p = 0.029). However, 5-HTTLPR genotypes were not significantly associated with remission (p > 0.05). Conclusions: Our results show that treatment response to escitalopram at 8 weeks was moderated by 5-HTTLPR, with better response rates for s allele carriers than for l allele homozygotes. Although the role of 5-HTTLPR as a definite predictor of selective serotonin reuptake inhibitor treatment response cannot be confirmed from current results, they do suggest a trend for better response in s allele carriers.
Renal Metanephric Adenoma Mimicking Papillary Renal Cell Carcinoma on Computed Tomography: A Case Report
Authors: Masuda Akinori , Kamai Takao , Mizuno Tomoya , Kambara Tsunehito , Abe Hideyuki , Tomita Shigeki , Fukabori Yoshitatsu , Yamanishi Tomonori , Kaji Yasushi , Yoshida Ken-ichiro
Published: October 2012

We present a case of renal metanephric adenoma (MA) mimicking papillary renal cell carcinoma (PRCC) on computed tomography (CT). In the present case, double-phase enhanced CT showed a hypovascular right renal tumor with gradual and prolonged enhancement. The renal tumor was surgically removed. Histological examination of the resected specimen showed renal MA. Although the radiological features of renal MA have been described by some authors, only a few reports have mentioned the pattern of enhancement on multiphase enhanced CT. The pattern of enhancement of a renal tumor is likely to be correlated with its pathological features. Since renal MA is thought to be genetically related to PRCC, these two tumors are likely to demonstrate similar radiological features, so that differentiating between them becomes difficult. In patients with a hypovascular renal mass that shows gradual and prolonged enhancement on multiphase enhanced CT, the diagnosis of renal MA should be considered.
A Novel Mouse Model of Podocyte Depletion
Authors: Wang L. , Tang Y. , Howell D.N. , Ruiz P. , Spurney R.F.
Published: October 2012

Aim: The goal of this study was to examine the capacity for glomerular repair after a podocyte-depleting injury. Methods: We created transgenic (TG) mice expressing the yeast enzyme cytosine deaminase specifically in glomerular podocytes. In these TG animals, the prodrug 5-flucytosine (5-FC) is converted to 5-fluorouracil and promotes cell death. Results: Treatment with increasing dosages of 5-FC caused graded increases in proteinuria 1–2 weeks after treatment, which returned to control levels by the 10-week time point. Light microscopic examination revealed minimal pathology at the 2-week time point, but electron microscopy revealed found foot process effacement as well as focal areas of glomerular basement membrane duplication, and immunohistochemical studies detected podocyte apoptosis and a decrease in the number of Wilms’ tumor protein 1 (WT1)-positive cells. By the 10-week time point, however, the number of WT1-positive cells was similar to controls and a few mice had developed focal areas of glomerulosclerosis. Consistent with the effects of 5-FC on podocyte number, expression of the podocyte mRNAs for nephrin, podocin, synaptopodin and podocalyxin were altered in a similar temporal fashion. Conclusion: The glomerulus has a significant capacity for repair after a podocyte-depleting injury.
Factors Associated with Chronic Kidney Disease Progression in Australian Nephrology Practices
Authors: Boudville Neil , Kemp Anna , Moody Henry , Fassett Robert G. , Pedagogos Eugenie , Nelson Craig , Healy Helen , Mangos George , Kirkland Geoff , Kay Troy , Champion de Crespigny Paul , Hoffman David , Waugh David ,   and on behalf of eKiDNAAl
Published: October 2012

Background/Aims: Chronic kidney disease (CKD) is a major health issue worldwide. The aim of this study was to explore factors associated with CKD progression in Australian nephrology practices. Methods: This was a retrospective study utilising an electronic medical record (EMR), Audit4 (Software for Specialists, Australia). The baseline visit was defined as the first entry into the EMR. The primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Results: 1,328 patients were included with a mean eGFR at baseline of 37.4 ± 0.7 ml/min/1.73 m2, a mean follow-up of 17.7 months and a mean annual rate of change in eGFR of –0.84 ± 0.26 ml/min/1.73 m2. Univariate analysis demonstrated that women, smokers, and patients prescribed erythropoiesis-stimulating agents (ESA) had a significantly more rapid decline in eGFR (p = 0.007, 0.033, and 0.003, respectively). On multivariate analysis: gender, age, prescription of ESA and phosphate binders, and baseline eGFR were significantly associated with CKD progression (p = 0.003, 0.004, <0.001, 0.029, and <0.001, respectively). Conclusions: This study identifies potential factors associated with CKD progression in a population referred to nephrologists, but current data quality may result in bias. Implementation of changes in the format of data collection is required so that busy clinicians record essential information to enable this to become a more accurate and reliable research tool.
Oxidative Stress, Macrophage Infiltration and CD163 Expression Are Determinants of Long-Term Renal Outcome in Macrohematuria-Induced Acute Kidney Injury of IgA Nephropathy
Authors: Gutiérrez Eduardo , Egido Jesús , Rubio-Navarro Alfonso , Buendía Irene , Blanco Colio Luis Miguel , Toldos Oscar , Manzarbeitia Felix , de Lorenzo Alberto , Sanchez Rosa , Ortiz Alberto , Praga Manuel , Moreno Juan Antonio
Published: October 2012

Background: Macroscopic hematuria (MH) may cause acute kidney injury (AKI) in IgA nephropathy. Up to 25% of patients with MH-associated AKI do not recover baseline renal function. Our objective was to identify subjects at high risk for an adverse renal function. Methods: We examined macrophages, oxidative stress markers (NADPH-p22 and HO-1) and the hemoglobin scavenger receptor (CD163) in renal biopsy specimens from 33 MH-AKI patients with complete recovery (CR, n = 17) or incomplete recovery (IR, n = 16) of renal function after 6.72 (range 0.5–21.5) years of follow-up. Results: CD163-expressing macrophages, HO-1 and NADPH-p22 expression were located in areas surrounding tubules with iron deposits and filled with erythrocyte casts. CD163-positive macrophages score and HO-1- and p22-positive staining correlated positively with percentage of tubules with erythrocyte casts and tubular necrosis. Macrophage infiltration, CD163-positive macrophage score, NADPH-p22- and HO-1-positive staining areas were significantly greater in IR patients when compared with CR patients. The CD163-positive macrophage score and oxidative stress markers (p22 and HO-1) were negatively correlated with renal function outcome, as determined by estimated glomerular filtration rate (eGFR) and proteinuria, at the end of the follow-up period. In multivariate analysis, the CD163-positive macrophage score remained significantly associated with final eGFR and proteinuria after adjustment by age, gender, duration of MH, initial eGFR and proteinuria. Conclusions: Increased macrophage infiltration, CD163 expression and oxidative stress are significant prognostic factors for an IR of renal function in patients with MH-associated AKI. These molecular pathways may be involved in the renal response to injury and could be useful to improve diagnosis and therapeutics.
Epidemiological Characteristics of Fournier’s Gangrene: A Report of 71 Patients
Authors: Aridogan I. Atilla , Izol Volkan , Abat Deniz , Karsli Onur , Bayazit Yildirim , Satar Nihat
Published: October 2012

Introduction: To identify the predisposing factors, etiological and clinical characteristics as well as the Fournier’s gangrene (FG) severity index (FGSI) in the outcomes of patients with FG. Materials and Methods: The data from 71 patients diagnosed with FG in a period of 17 years were retrospectively reviewed for the age of the patient, their history, predisposing factors, etiology, prodromal symptoms, FGSI, culture results, hospitalization period, surgical interventions, responses to the therapy and complications. Results: All of the patients were Caucasian males, and the mean age was 61.3 (range 36–92) years. The mean duration from the onset of symptoms to surgery was 7.5 days. The mean hospitalization time was 27.4 days and the most common etiological factor for FG was a perineal abscess. The overall mortality rate was 29.6%. The relationship between the number of predisposing factors and mortality rates in patients with FG was the most statistically significant parameter (p = 0.001). Conclusions: Multiple predisposing factors predict a poor prognosis and correlate significantly with mortality. Extension of the disease and the FGSI score were not predictive of outcome. The most essential intervention for stopping the rapidly progressing infectious process of FG consists of early recognition of the disease, proper management of the predisposing factors and aggressive surgical debridement. Such an intervention can improve clinical outcomes.