bluuebunny/crossref_metadata_2025 huggingface dataset:
Getting the message across: mechanisms of physiological cross talk by adipose tissue
Authors: Lee Do-Eun , Kehlenbrink Sylvia , Lee Hanna , Hawkins Meredith , Yudkin John S.
Published: March 2009

Obesity is associated with resistance of skeletal muscle to insulin-mediated glucose uptake, as well as resistance of different organs and tissues to other metabolic and vascular actions of insulin. In addition, the body is exquisitely sensitive to nutrient imbalance, with energy excess or a high-fat diet rapidly increasing insulin resistance, even before noticeable changes occur in fat mass. There is a growing acceptance of the fact that, as well as acting as a storage site for surplus energy, adipose tissue is an important source of signals relevant to, inter alia, energy homeostasis, fertility, and bone turnover. It has also been widely recognized that obesity is a state of low-grade inflammation, with adipose tissue generating substantial quantities of proinflammatory molecules. At a cellular level, the understanding of the signaling pathways responsible for such alterations has been intensively investigated. What is less clear, however, is how alterations of physiology, and of signaling, within one cell or one tissue are communicated to other parts of the body. The concepts of cell signals being disseminated systemically through a circulating “endocrine” signal have been complemented by the view that local signaling may similarly occur through autocrine or paracrine mechanisms. Yet, while much elegant work has focused on the alterations in signaling that are found in obesity or energy excess, there has been less attention paid to ways in which such signals may propagate to remote organs. This review of the integrative physiology of obesity critically appraises the data and outlines a series of hypotheses as to how interorgan cross talk takes place. The hypotheses presented include the “fatty acid hypothesis,”, the “portal hypothesis,”, the “endocrine hypothesis,”, the “inflammatory hypothesis,”, the “overflow hypothesis,”, a novel “vasocrine hypothesis,” and a “neural hypothesis,” and the strengths and weaknesses of each hypothesis are discussed.
Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein
Authors: Chen Junqin , Cha-Molstad Hyunjoo , Szabo Anna , Shalev Anath
Published: March 2009

Cardiomyocyte apoptosis is a critical process in the pathogenesis of ischemic and diabetic cardiomyopathy, but the mechanisms are not fully understood. Thioredoxin-interacting protein (TXNIP) has recently been shown to have deleterious effects in the cardiovascular system and we therefore investigated whether it may also play a role in diabetes-associated cardiomyocyte apoptosis. In fact, TXNIP expression was increased in H9C2 cardiomyocytes incubated at high glucose, and cardiac expression of TXNIP and cleaved caspase-3 were also elevated in vivo in streptozotocin- and obesity-induced diabetic mice. Together, these findings not only suggest that TXNIP is involved in diabetic cardiomyopathy but also that it may represent a novel therapeutic target. Surprisingly, testing putative TXNIP modulators revealed that calcium channel blockers reduce cardiomyocyte TXNIP transcription and protein levels in a dose-dependent manner. Oral administration of verapamil for 3 wk also reduced cardiac TXNIP expression in mice even in the face of severe diabetes, and these reduced TXNIP levels were associated with decreased apoptosis. To determine whether lack of TXNIP can mimic the verapamil-induced decrease in apoptosis, we used TXNIP-deficient HcB-19 mice, harboring a natural nonsense mutation in the TXNIP gene. Interestingly, we found significantly reduced cleaved caspase-3 levels in HcB-19 hearts, suggesting that TXNIP plays a critical role in cardiac apoptosis and that the verapamil effects were mediated by TXNIP reduction. Thus our results suggest that TXNIP reduction is a powerful target to enhance cardiomyocyte survival and that agents such as calcium channel blockers may be useful in trying to achieve this goal and prevent diabetic cardiomyopathy.
Baroreflex sensitivity varies during the rat estrous cycle: role of gonadal steroids
Authors: Goldman Robert K. , Azar Afaf S. , Mulvaney Julia M. , Hinojosa-Laborde Carmen , Haywood Joseph R. , Brooks Virginia L.
Published: March 2009

Baroreflex sensitivity (BRS) increases in women during the luteal phase of the menstrual cycle, when gonadal hormones are elevated, but whether a similar cycle-dependent variation in BRS occurs in rats is unknown. In addition, whether cyclic BRS changes depend on gonadal steroids has not been previously investigated. To test these hypotheses, BRS was determined in cycling female rats using two approaches: 1) baroreflex control of renal sympathetic nerve activity (RSNA) in anesthetized rats; 2) cardiovagal spontaneous BRS (sBRS) in conscious rats instrumented for continuous telemetric measurements of mean arterial pressure (MAP) and heart rate (HR). MAP, HR, and sBRS were also measured in rats 2–3 and 5–6 wk following ovariectomy (OVX), to eliminate gonadal steroids. In anesthetized rats, RSNA BRS gain was increased ( P < 0.01) during proestrus (−4.8±0.5% control/mmHg) compared with diestrus/estrus (−2.8 ± 0.3% control/mmHg). Similarly, a proestrous peak in sBRS was observed in conscious rats (1.66 ± 0.07 ms/mmHg, proestrus; 1.48 ± 0.06 ms/mmHg, diestrus/estrus; P < 0.001). OVX eliminated estrous cycle-induced variation in sBRS. In addition, OVX reduced ( P < 0.05) diurnal variations in MAP (5.9 ± 0.3 vs. 3.9 ± 0.5 mmHg) and HR [54 ± 4 vs. 39 ± 3 beats per minute (bpm)], and abolished diurnal variations in sBRS. Finally, while MAP, HR, and sBRS were decreased 2–3 wk following OVX, ∼3 wk later, MAP and sBRS increased, and HR decreased further. No changes in MAP, HR, or sBRS were seen with time in sham OVX controls. In summary, RSNA and cardiovagal sBRS vary during the rat estrous cycle, and this variation is abolished by OVX. We conclude that sex steroid hormones are required for both cyclic and diurnal changes in BRS in rats.
Small Molecule XIAP Inhibitors Enhance TRAIL-Induced Apoptosis and Antitumor Activity in Preclinical Models of Pancreatic Carcinoma
Authors: Vogler Meike , Walczak Henning , Stadel Dominic , Haas Tobias L. , Genze Felicitas , Jovanovic Marjana , Bhanot Umesh , Hasel Cornelia , Möller Peter , Gschwend Jürgen E. , Simmet Thomas , Debatin Klaus-Michael , Fulda Simone
Published: March 2009

Evasion of apoptosis is a characteristic feature of pancreatic cancer, a prototypic cancer that is refractory to current treatment approaches. Hence, there is an urgent need to design rational strategies that counter apoptosis resistance. To explore X-linked inhibitor of apoptosis (XIAP) as a therapeutic target in pancreatic cancer, we analyzed the expression of XIAP in pancreatic tumor samples and evaluated the effect of small molecule XIAP inhibitors alone and in combination with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) against pancreatic carcinoma in vitro and in vivo. Here, we report that XIAP is highly expressed in pancreatic adenocarcinoma samples compared with normal pancreatic ducts. Small molecule XIAP inhibitors synergize with TRAIL to induce apoptosis and to inhibit long-term clonogenic survival of pancreatic carcinoma cells. In contrast, they do not reverse the lack of toxicity of TRAIL on nonmalignant cells in vitro or normal tissues in vivo, pointing to a therapeutic index. Most importantly, XIAP inhibitors cooperate with TRAIL to trigger apoptosis and suppress pancreatic carcinoma growth in vivo in two preclinical models, i.e., the chorioallantoic membrane model and a mouse xenograft model. Parallel immunohistochemical analysis of tumor tissue under therapy reveals that the XIAP inhibitor acts in concert with TRAIL to cause caspase-3 activation and apoptosis. In conclusion, our findings provide, for the first time, evidence in vivo that XIAP inhibitors prime pancreatic carcinoma cells for TRAIL-induced apoptosis and potentiate the antitumor activity of TRAIL against established pancreatic carcinoma. These findings build the rationale for further (pre)clinical development of XIAP inhibitors and TRAIL against pancreatic cancer. [Cancer Res 2009;69(6):2425–34]
Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma
Authors: Avnet Sofia , Sciacca Laura , Salerno Manuela , Gancitano Giovanni , Cassarino Maria Francesca , Longhi Alessandra , Zakikhani Mahvash , Carboni Joan M. , Gottardis Marco , Giunti Armando , Pollak Michael , Vigneri Riccardo , Baldini Nicola
Published: March 2009

Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and >IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HRA). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti–IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HRA, and IGFIR) act complementarily for an IGF-II–mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth. [Cancer Res 2009;69(6):2443–52]
The Putative Tumor Suppressor microRNA-101 Modulates the Cancer Epigenome by Repressing the Polycomb Group Protein EZH2
Authors: Friedman Jeffrey M. , Liang Gangning , Liu Chun-Chi , Wolff Erika M. , Tsai Yvonne C. , Ye Wei , Zhou Xianghong , Jones Peter A.
Published: March 2009

The Polycomb Repressive Complex 2 (PRC2) mediates epigenetic gene silencing by trimethylating histone H3 lysine 27 (H3K27me3) and is known to aberrantly silence tumor suppressor genes in cancer. EZH2, the catalytic subunit of PRC2, enhances tumorigenesis and is commonly overexpressed in several types of cancer. Our microRNA profiling of bladder transitional cell carcinoma (TCC) patient samples revealed that microRNA-101 (miR-101) is down-regulated in TCC, and we showed that miR-101 inhibits cell proliferation and colony formation in TCC cell lines. Furthermore, our results confirm that miR-101 directly represses EZH2 and stable EZH2 knockdowns in TCC cell lines create a similar growth suppressive phenotype. This suggests that abnormal down-regulation of miR-101 could lead to the overexpression of EZH2 frequently seen in cancer. We conclude that miR-101 may be a potent tumor suppressor by altering global chromatin structure through repression of EZH2. [Cancer Res 2009;69(6):2623–9]
Natural Killer Cells Require Selectins for Suppression of Subcutaneous Tumors
Authors: Sobolev Olga , Stern Patrick , Lacy-Hulbert Adam , Hynes Richard O.
Published: March 2009

Natural killer (NK) cells recognize and destroy cancer cells through a variety of mechanisms. They may also modulate the adaptive immune response to cancer by interacting with dendritic cells and T cells. Although NK cells play an important role in tumor suppression, little is known about the mechanisms of their recruitment to tumors. Previously it has been shown that subcutaneous tumor growth is enhanced in mice lacking selectins, a family of cell adhesion molecules that mediate the first step of immune cell entry into tissue from the blood. Here we show that NK cell recruitment to tumors is defective in selectin-deficient mice. In vivo NK cell depletion, either pharmacologic or genetic, leads to enhanced subcutaneous tumor growth, similar to the phenotype observed in the selectin-deficient animals. We also show that although NK cells from selectin-deficient mice appear developmentally normal and are functional in in vitro assays, their in vivo function is impaired. This study reveals a role for selectins in NK cell recruitment to tumors and in regulation of effective tumor immunity. [Cancer Res 2009;69(6):2531–9]
Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer
Authors: Singer Stephan , Malz Mona , Herpel Esther , Warth Arne , Bissinger Michaela , Keith Martina , Muley Thomas , Meister Michael , Hoffmann Hans , Penzel Roland , Gdynia Georg , Ehemann Volker , Schnabel Philipp Albert , Kuner Ruprecht , Huber Peter , Schirmacher Peter , Breuhahn Kai
Published: March 2009

Dynamic instability of the microtubule network modulates processes such as cell division and motility, as well as cellular morphology. Overexpression of the microtubule-destabilizing phosphoprotein stathmin is frequent in human malignancies and represents a promising therapeutic target. Although stathmin inhibition gives rise to antineoplastic effects, additional and functionally redundant microtubule-interacting proteins may attenuate the efficiency of this therapeutic approach. We have systematically analyzed the expression and potential protumorigenic effects of stathmin family members in human non–small cell lung cancer (NSCLC). Both stathmin and stathmin-like 3 (SCLIP) were overexpressed in adenocarcinoma as well as squamous cell carcinoma (SCC) tissues and induced tumor cell proliferation, migration, and matrix invasion in respective cell lines. Accordingly, reduced stathmin and SCLIP levels affected cell morphology and were associated with a less malignant phenotype. Combined inhibition of both factors caused additive effects on tumor cell motility, indicating partial functional redundancy. Because stathmin and SCLIP expression significantly correlated in NSCLC tissues, we searched for common upstream regulators and identified the far upstream sequence element-binding protein-1 (FBP-1) as a pivotal inducer of several stathmin family members. Our results indicate that the coordinated overexpression of microtubule-destabilizing factors by FBP-1 is a critical step to facilitate microtubule dynamics and subsequently increases proliferation and motility of tumor cells. [Cancer Res 2009;69(6):2234–43]
Fibroblast Growth Factor Receptor 1–Transformed Mammary Epithelial Cells Are Dependent on RSK Activity for Growth and Survival
Authors: Xian Wa , Pappas Leontios , Pandya Darshan , Selfors Laura M. , Derksen Patrick W. , de Bruin Michiel , Gray Nathanael S. , Jonkers Jos , Rosen Jeffrey M. , Brugge Joan S.
Published: March 2009

Fibroblast growth factor receptor 1 (FGFR1) is frequently amplified and highly expressed in lobular carcinomas of the breast. In this report, we evaluated the biological activity of FGFR1 in a wide range of in vitro assays. Conditional activation of FGFR1 in the nontransformed MCF10A human mammary cell line, MCF10A, resulted in cellular transformation marked by epidermal growth factor–independent cell growth, anchorage-independent cell proliferation and survival, loss of cell polarity, and epithelial-to-mesenchymal transition. Interestingly, small-molecule or small interfering RNA inhibition of ribosomal S6 kinase (RSK) activity induced death of the FGFR1-transformed cells, but not of the parental MCF10A cell line. The dependence of FGFR1-transformed cells on RSK activity was further confirmed in cell lines derived from mouse and human lobular carcinomas that possess high FGFR1 activity. Taken together, these results show the transforming activity of FGFR1 in mammary epithelial cells and identify RSK as a critical component of FGFR1 signaling in lobular carcinomas, thus implicating RSK as a candidate therapeutic target in FGFR1-expressing tumors. [Cancer Res 2009;69(6):2244–51]
Antitumor Effect of Retinoic Acid Receptor-β2 Associated with Suppression of Cyclooxygenase-2
Authors: Song Shumei , Guan Baoxiang , Men Taoyan , Hoque Ashraful , Lotan Reuben , Xu Xiao-Chun
Published: March 2009

Retinoic acid receptor-β2 (RAR-β2) is a putative tumor suppressor gene in various cancers. To determine the underlying molecular mechanisms, we transfected RAR-β2 cDNA into esophageal cancer TE-1 and TE-8 cells and found that RAR-β2 suppressed tumor cell growth in vitro and tumor formation in nude mice in TE-8 cells, whereas the stable transfection of RAR-β2 did not restore retinoid sensitivity or inhibit tumor formation in nude mouse in TE-1 cells. Molecularly, we revealed that RAR-β2 antitumor activity was associated with expression and suppression of cyclooxygenase-2 (COX-2) in these tumor cell lines. Moreover, antisense RAR-β2 cDNA induced COX-2 expression in TE-3 cells. Furthermore, when COX-2 expression is first blocked by using antisense COX-2 expression vector, the effect of RAR-β2 is diminished in these tumor cells. In addition, we analyzed expression of RAR-β2 and COX-2 mRNA in tissue specimens and found that RAR-β2 expression is associated with low levels of COX-2 expression in esophageal cancer tissues. Induction of RAR-β2 expression in oral leukoplakia tissues after the patients treated with 13-cis RA correlated with a reduction in COX-2 expression and clinical response. Our findings indicate that some of RAR-β2 antitumor activities are mediated by suppression of COX-2 expression in some of these esophageal cancer cells. After correlating antitumor effect of RAR-β2 with COX-2 expression in the published studies, we also found the association. Thus, further studies will determine whether manipulation of COX-2 expression in different cancers can antagonize RAR-β2 activity.
Craniectomy for a Bilobed Dermoid Cyst in the Temporal Fossa and Greater Wing of the Sphenoid Bone
Authors: Nevrekar Dipti , Abdu Emun , Selden Nathan R.
Published: March 2009

Dermoid cysts are common periorbital lesions. They usually occur near the superolateral orbital rim, indenting but not extending within the bony outer table. We present an unusual case of a dumbbell-shaped dermoid cyst underlying the temporalis muscle with extension into the lateral wing of the greater sphenoid bone, approaching the optic canal. The cyst was successfully removed en bloc via a small skull base craniectomy without spillage of cyst contents. The patient recovered well without neurological or visual sequelae.
Hemorrhage in Brain Stem Cavernoma Presenting with Torticollis
Authors: Agrawal Amit , Cincu Rafael , Joharapurkar S.R. , Bhake Arvind , Hiwale Kishore M.
Published: March 2009

Spasmodic torticollis due to an identified focal brain stem lesion is uncommon and abrupt-onset spasmodic torticollis due to midbrain lesions in humans is rarely reported. A 9-year-old female child who had fallen off a bicycle and had lost consciousness for 10 min, vomiting 2–3 times, developed acute torticollis immediately after the injury. Examinations suggested hemorrhage in brain stem cavernoma. A search of the literature written in English revealed that this type of presentation has not been reported previously.
Hepatitis C Virus Genotype in Blood Donors and Associated Liver Disease in Indonesia
Authors: Utama Andi , Budiarto Bugi Ratno , Monasari Dewi , Octavia Theresia Imelda , Chandra Ivan Stevanus , Gani Rino Alvani , Hasan Irsan , Sanityoso Andri , Miskad Upik Anderiani , Yusuf Irawan , Lesmana Laurentius Adrianus , Sulaiman Ali , Tai Susan
Published: March 2009

Objective: The aim of this study was to investigate the distribution of hepatitis C virus (HCV) genotype and the possible association between genotype and HCV-associated liver disease in Indonesia. Methods: 32 anti-HCV-positive asymptomatic carriers (AC), 55 chronic hepatitis (CH), 41 liver cirrhosis (LC), and 35 hepatocellular carcinoma (HCC) patients were included in this study. HCV genotyping was performed by phylogenetic analysis of the NS5B and 5′-UTR regions. Results: The HCV subtype 1b (36.5%), based on NS5B region, was the most prevalent, followed by subtypes 3k (15.4%), 2a (14.4%), 1a (12.5%) and 1c (12.5%), and 2e (4.8%). Subtypes 2f, 3a, 3b, and 4a were also found in some of the samples. HCV subtypes 3k (40.0%) and 1a (35.0%) were the two major subtypes in AC. HCV subtype 1b was not found in AC, but it was common in CH (31.3%), LC (50.0%), and HCC (57.1%). Conclusion: HCV subtype 1b was prevalent in samples of HCV-associated liver disease patients, including CH, LC and HCC. The percentage of subtype 1b was increased with the disease severity (AC < CH < LC < HCC).
Molecular Epidemiology of Noroviruses Detected in Food Handler-Associated Outbreaks of Gastroenteritis in Japan
Authors: Shinkawa Naomi , Noda Mamoru , Yoshizumi Shima , Tokutake Yumi , Shiraishi Takashi , Arita-Nishida Tomoko , Nishio Osamu , Oka Tomoichiro , Hansman Grant S. , Takeda Naokazu , Kimura Hirokazu
Published: March 2009

Twelve outbreaks of food handler-associated gastroenteritis between November 2002 and March 2006 in Japan were examined for norovirus (NoV) using RT-PCR and sequence analysis. NoV was detected in 77 of 81 customers and 45 of 104 food handlers. Identical NoV sequences were detected in patients and food handlers in each outbreak.
SERCA Inhibition Limits the Functional Effects of Cyclic GMP in Both Control and Hypertrophic Cardiac Myocytes
Authors: Zhang Qihang , Davidov Tomer , Weiss Harvey R. , Scholz Peter M.
Published: March 2009

The negative functional effects of cyclic GMP are controlled by the sarcoplasmic reticulum calcium-ATPase (SERCA). The effects of cyclic GMP are blunted in cardiac hypertrophy. We tested the hypothesis that the interaction between cyclic GMP and SERCA would be reduced in hypertrophic cardiac myocytes. Myocytes were isolated from 7 control and 7 renal-hypertensive hypertrophic rabbits. Control and hypertrophic myocytes received 8-bromo-cGMP (8-Br-cGMP; 10–7, 10–6, 10–5 mol/l), the SERCA blocker thapsigargin (10–8 mol/l) followed by 8-Br-cGMP, or the SERCA blocker, cyclopiazonic acid (CPA; 10–7 mol/l) followed by 8-Br-cGMP. Percent shortening and maximal rate of shortening and relaxation were recorded using a video edge detector. Changes in cytosolic Ca2+ were assessed in fura 2-loaded myocytes. In controls, 8-Br-cGMP caused a significant 36% decrease in percent shortening from 5.8 ± 0.4 to 3.7 ± 0.3%. Thapsigargin and CPA did not affect basal control or hypertrophic myocyte function. When 8-Br-cGMP was given following thapsigargin or CPA, the negative effects of 8-Br-cGMP on control myocyte function were reduced. In hypertrophic myocytes, 8-Br-cGMP caused a smaller but significant 17% decrease in percent shortening from 4.7 ± 0.2 to 3.9 ± 0.1%. When 8-Br-cGMP was given following thapsigargin or CPA, no significant changes occurred in hypertrophic cell function. Intracellular Ca2+ transients responded in a similar manner to changes in cell function in control and hypertrophic myocytes. These results show that the effects of cyclic GMP were reduced in hypertrophic myocytes, but this was not related to SERCA. In presence of SERCA inhibitors, the responses to cyclic GMP were blunted in hypertrophic as well as control myocytes.
Phase II Study of Docetaxel and Gefitinib as Second-Line Therapy in Gemcitabine Pretreated Patients with Advanced Pancreatic Cancer
Authors: Brell Joanna M. , Matin Khalid , Evans Terry , Volkin Robert L. , Kiefer Gauri J. , Schlesselman James J. , Dranko Shelley , Rath Linda , Schmotzer Amy , Lenzner Diana , Ramanathan Ramesh K.
Published: March 2009

Background: There is no standard second-line therapy for advanced pancreatic cancer (APC). We evaluated the epidermal growth factor receptor (EGFR) inhibitor gefitinib and docetaxel in a phase II study following gemcitabine failure. Methods: EGFR overexpression was not required. The initial docetaxel dose was 75 mg/m2 on day 1 every 21 days. Due to febrile neutropenia in 8 of the first 18 patients, the dose was reduced to 60 mg/m2. Gefitinib, 250 mg/day orally, was given continuously. Results: Forty-one patients received treatment and were evaluable. Febrile neutropenia was seen in 11 patients (27%), with most events occurring at the docetaxel dose of 75 mg/m2 (8 of 18 patients). Common treatment-related grade 3/4 toxicities were: fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). There was 1 partial response and stable disease in 19 patients. Time to progression was 1.8 months and median survival was 4.5 months (95% CI 2.9–5.7). Conclusion: The tolerability and feasibility of second-line therapy for APC was demonstrated. The combination of gefitinib and docetaxel showed evidence of limited efficacy.
The Relationship between the Glucose Transporter Type 1 Expression and 18F-Fluorodeoxyglucose Uptake in Esophageal Squamous Cell Carcinoma
Authors: Hiyoshi Yukiharu , Watanabe Masayuki , Imamura Yu , Nagai Youhei , Baba Yoshifumi , Yoshida Naoya , Toyama Eiichiro , Hayashi Naoko , Baba Hideo
Published: March 2009

Objective: Glucose transporter type 1 (Glut1) has been reported to be present in several types of carcinomas. The aims of this study are to evaluate Glut1 expression in both primary tumors and metastatic lymph nodes (LNs) of esophageal squamous cell carcinoma (ESCC) and to assess the relationship between Glut1 expression and 18F-fluorodeoxyglucose (FDG) accumulation. Methods: We immunohistochemically examined the expression of Glut1 in 60 surgically resected primary lesions and 95 metastatic LNs of ESCC and classified them into 3 groups. The FDG accumulation was assessed with a positron emission tomography (PET). Results: In the primary tumors, a high Glut1 expression was found to be significantly associated with advanced lesions: depth of tumor (p < 0.01), LN metastasis (p < 0.05) and advanced pathological stage (p < 0.01). The Glut1 expression of the metastatic LNs significantly correlated with that of each primary tumor (p < 0.001). The PET-positive lesions had a larger size and higher Glut1 expression than the PET-negative lesions in both the primary tumors and metastatic LNs. Conclusions: In both the primary tumors and metastatic LNs of ESCC, the Glut1 expression and tumor size correlated with the FDG accumulation and influence the sensitivity of the PET scan.
A Randomized, Placebo-Controlled, Exploratory Trial of Ibuprofen and Pseudoephedrine in the Treatment of Primary Nocturnal Enuresis in Children
Authors: Gelotte Cathy K. , Prior Mary Jane , Gu Joan
Published: March 2009

This exploratory randomized, double-blind, double-dummy, placebo-controlled trial of 14 days duration conducted in 22 primary care practices in the United States was used to compare the efficacy of ibuprofen and pseudoephedrine, administered alone or in combination, to placebo for the treatment of primary nocturnal enuresis (PNE) in children aged 6 to 11 years. Ibuprofen (IBU) and pseudoephedrine (PSE) are not approved for the treatment of PNE. Three hundred eighteen children with PNE were enrolled. Eligible children had ≥ 8 wet nights during a 14-day baseline. Each child was randomly assigned to 1 of 4 treatment groups: IBU 12.5 mg/kg and PSE HCl 15 or 30 mg (depending on weight) (n = 82), IBU 12.5 mg/kg (n = 78), PSE HCl 15 or 30 mg (n = 76), or placebo (n = 82). Treatment was administered orally at bedtime for 14 days. Caregivers recorded whether the child was wet or dry each night in a daily diary. Children in the IBU alone and IBU and PSE combined groups had greater mean reductions from baseline in the number of wet nights (primary end point) compared to children receiving placebo (-2.9, -2.9, and -1.4, respectively, P < .005); PSE alone (-1.8) was not significantly different from placebo. Children in these groups also had greater mean percentage reductions in the number of wet nights compared to placebo-treated children (26%, 28%, and 12%, respectively). Although not always statistically significant, secondary end points improved in the IBU alone and IBU and PSE combined treatment groups, which included decreases in mean number of wet nights and decreases in the number and percentage of children with ≥ 50%, 40%, 30%, or 25% reductions in number of wet nights. Children responding to treatment had larger mean bladder capacities and larger mean percentage of predicted bladder capacities than children who did not respond in each treatment group. No significant differences in adverse events were found among treatment groups. In conclusion, in this exploratory study in children aged 6 through 11 years, IBU provided a beneficial effect in the treatment of PNE compared to placebo, whereas PSE did not. The addition of PSE to IBU did not enhance or diminish the efficacy of IBU. All treatments were well tolerated.
The Political Economy of Authoritarian Single-Party Dominance
Authors: Greene Kenneth F.
Published: March 2009

Why do authoritarian dominant parties, once established, continue to win elections or lose power? Employing a time-series cross-national analysis of election outcomes and two country case studies, the author shows that dominant parties endure despite poor economic performance, voter demand for new parties, and sufficiently permissive electoral institutions. Instead, the author demonstrates that dominant parties continue to win when they can politicize public resources, and they fail when privatizations put the state’s fiscal power out of their reach.The argument has implications for the fate of dominant parties, transitions to democracy in competitive authoritarian regimes, and the study of incumbency advantages and electoral fairness in comparative politics.
Surface Modification of Phosphogypsum Used as Reinforcing Material in Polyethylene Composites
Authors: Denev Yordan G. , Denev Georgi D. , Popov Anton N.
Published: March 2009

The possibilities for modifying the surface of phosphogypsum (CaSO 4 · 2H2O) used as reinforcing material in polyethylene (PE) composites are investigated. The used method for surface modification of filler is the treatment with polyethylene glycol (PEG). The product has improved properties of compatibility with organic phase (polymer matrix). The use of PEG as modifier is described. The surface modified phosphogypsum and reinforcement materials have improved the properties including tensile strength. The optimum amount of PEG used for surface modification is 1—3%. These modified fillers and reinforcement materials may be used in a wide range of applications. The present study relates to a method for the surface modification of waste phosphogypsum and to their use in PE composites. The change in the surface characteristics of the filler influences also the properties of the composites in which they are used.
Crosslinking Kinetics of Blends of Ethylene Vinyl Acetate and Ground Tire Rubber
Authors: Bianchi O. , Fiorio R. , Martins J.N. , Zattera A.J. , Scuracchio C.H. , Canto L.B.
Published: March 2009

The copolymer ethylene vinyl acetate (EVA) and blends of EVA and ground tire rubber (GTR) with different compositions are prepared in the presence and absence of dicumyl peroxide (DCP) as a crosslinking agent. The crosslinking kinetics is investigated through oscillatory disc rheometry (ODR) and differential scanning calorimetry (DSC). The crosslinking kinetics is found to be dependent on the amount of GTR in the EVA/GTR blends; the partially crosslinked GTR phase acts as a physical barrier, slowing down the EVA crosslinking rate. Furthermore, activation energies (Ea) and reaction order (n) values suggest that the crosslinking reactions are not restricted to the EVA bulk, but can also occur to some extent at the EVA/GTR interface.
Organizational Risk after Modernism
Authors: Miller Kent D.
Published: March 2009

This study identifies the modernist assumptions in organizational risk research, along with their historical origin and limitations. Risk research from a modernist perspective focuses primarily on individuals, treats risk preferences as exogenously given, attempts to quantify risk, assumes that risk reflects a given probability distribution, omits ethical considerations, and neglects actions by focusing on decision making. This study proposes a contrasting postmodern perspective on organizational risk. By this view, risk is a social and multilevel phenomenon; risk preferences, perceptions, and responses are learned; risk is subjectively perceived and often unquantifiable; the environment is a complex, socially constructed system; ethical considerations are integral to risk assessment and management; and organizations respond to risk through their actions, not just by making decisions. These themes motivate new directions for organizational risk research.
Making Good Sense: Assessing the Quality of Risky Decision-making
Authors: Winch Graham M. , Maytorena Eunice
Published: March 2009

How good are managers at making risky decisions? Recent research has identified this gap in decision-making research; this paper attempts to address this question in the context of risky decision-making. Following a review of the behavioural decision-making and sensemaking schools of research on risky decision-making, a research methodology is presented which is derived from a critique of the former school to address limitations of the research of the latter school. A combination of active information search and cognitive mapping was deployed to assess the performance of 45 project managers in identifying project risks. The findings show that some managers perform better than others at this type of decision-making due to the differences in the ways in which they tackle the problem. The concluding discussion argues that the two schools are more complementary than antithetical.
Moving Beyond Normal Accidents and High Reliability Organizations: A Systems Approach to Safety in Complex Systems
Authors: Leveson Nancy , Dulac Nicolas , Marais Karen , Carroll John
Published: March 2009

In this century society faces increasingly large-scale accidents and risks emerging from our own wondrous technologies. Two prominent organizational approaches to safety, Normal Accident Theory and High Reliability Organizations, have focused attention on a variety of industries that deal with hazardous situations, developed concepts to explicate organizational structure and culture, and debated whether accidents are inevitable in complex systems. We outline these approaches and identify some limitations, including narrow definitions, ambiguity about key concepts, confusion of reliability and safety, and overly pessimistic or optimistic conclusions. We believe that the debate between NAT and HRO can become a more productive three-way conversation by including a systems approach to safety emerging from engineering disciplines. The more comprehensive systems approach clarifies the strengths and weaknesses of NAT and HRO and offers a more powerful repertoire of analytic tools and intervention strategies to manage and control post modern risk in complex, high-tech, systems with their potential for catastrophic disruptions and losses.
The Construction of General Public Interest: Risk, Legitimacy, and Power in a Public Hearing
Authors: Topal Cagri
Published: March 2009

The decisions of the economic actors in late modern society produce risks in addition to products and services. Thus, the parties likely to be affected by those decisions — individuals, communities, and society at large — seek to influence them. Public hearings are a key forum in society where this influence occurs. This paper uses a case study of a hearing to show how public hearings use legitimating practices to enact institutional power although they are commonly portrayed as risk-minimizing democratic mechanisms. Public hearings enact participation that is formal not substantive, create `public good' that serves particular not general interests, and use evaluation which is normative or value-based and not rational. Public hearings thus legitimate government and corporate institutions through the demonstration of citizen participation, general interest, and rational evaluation. These processes enact ideological or image-based legitimation by constructing an image of the general public. This legitimation is illusory but effective for enacting state and corporate power.
Predictors of Successful Diabetes Management in Low-Income Hispanic People
Authors: Latham Christine L. , Calvillo Evelyn
Published: March 2009

The specific aim of this predictive, correlational study was to test a culturally sensitive diabetes-specific health protection model to determine predictors of successful diabetes management in a newly diagnosed, type 2, low-income Hispanic population. Using a research-based Hispanic Health Protection Model (HHPM) as a framework, 240 adult participants with low levels of acculturation, strong beliefs about illness attribution and control of health, and low literacy levels were interviewed in a three-phase process over 4 to 6 months. The data analysis resulted in support of the HHPM based on relationships between 11 variables in four partial structural equation models, including lifestyle profile, acculturation, health beliefs, professional and social support, self-efficacy, diabetes knowledge, quality of life (self-satisfaction and impact of diabetes), and changes in hemoglobin a1c and body mass index. The study established carefully translated measures that held up to strong psychometric criteria. There was support for the HHPM for this population, and the results suggest future intervention with strengthening enablers, such as professional support and diabetes self-efficacy, in relation to this group's health beliefs.
Cognitive and language acquisition in typical and aided language learning: A review of recent evidence from an aided communication perspective
Authors: Murray Janice , Goldbart Juliet
Published: March 2009

Augmentative and alternative communication (AAC) is a discipline that has seen recent developments as a consequence of the worldwide technological revolution. Children with complex communication needs, who benefit from such systems, are now afforded an opportunity to develop independent communication skills.

The aim of this paper is to review theory and research relating to language acquisition in typical and aided language learning. Becoming a skilled aided communicator takes many years, but as this review demonstrates, little is known about the processes of skill development. In particular there is limited research evidence to support current language and communication intervention strategies typically used by practitioners working in the field of AAC. This review synthesizes current knowledge within an evidence-based framework and provides a summary to support practice and future research activity.
The content of children's definitions: The oral-written distinction
Authors: Marinellie Sally A.
Published: March 2009

The extant literature on oral and written language has shown several interesting differences in terms of production and style. The purpose of the present study was to investigate the content of word definitions provided by children in both the oral and written modes. A total of 30 typically developing children (mean age: 9 years; 2 months) defined common nouns in the oral and written modes. The definitions were coded for use of categorical terms (e.g., apple: fruit) and attributes (e.g., apple: red). The findings indicated that children displayed different types of word knowledge in the two modes, with written definitions generally having the advantage for production of categorical terms. Results are discussed with respect to the higher level of planning that is generally involved in written language compared to oral language. Implications for assessment and education are also discussed. This study expands the extant literature on how mode of language production can exert a considerable influence on a child's display of lexical knowledge.
Alliance Formation Motives in SMEs
Authors: Van Gils Anita , Zwart Peter S.
Published: March 2009

Cooperative agreements are important tools to improve the competitive position of small and medium-sized firms.This explorative conjoint analysis study simultaneously examines the importance of firm, environmental and partner motives on the formation of two types of SME-alliances. In addition, we study the influence of the sector of industry and the CEOs' characteristics. Results indicate that alliance formation is determined by a combination of organizational, partner-and industry-related motives, and that each of these factors should not be studied in isolation. Moreover, motives differ across functional area types of alliances, and both the sector of industry and a CEO's experience affect the probability of alliance creation.
The Effectiveness of TQM
Authors: Martínez-Costa Micaela , Jiménez-Jiménez Daniel
Published: March 2009

Total quality management is frequently considered to be a means for achieving competitive advantage. Small businesses have several limitations when they implement quality practices. However, total quality practices can foster the creation of the indispensable knowledge for continuous improvement and for competing in the current markets.The management of knowledge has also been identified as an important antecedent of performance. Using structural equations modelling, this article analyses the linkages between total quality management, organizational learning and performance.The most significant implication of this article is that small businesses should pay more attention to total quality management practices, as these can support both knowledge management practices and organizational performance.
The Relationship Between Emotional State and Success in Community Reintegration for Ex-Prisoners
Authors: Shinkfield Alison J. , Graffam Joe
Published: March 2009

This study examines the role of emotional state in the reintegration of ex-prisoners. Participants were 101 adult prisoners (72 male, 29 female) who completed a questionnaire 1 month prior to their release and at two postrelease points focusing, first, on prison-related experiences and, second, on the quality of life conditions experienced following release. The Beck Depression Inventory (BDI-II) and the Beck Anxiety Inventory were also completed at each interview. Results indicate that mean BDI-II scores were significantly higher at prerelease than postrelease, while mean anxiety scores were unchanged over the period under investigation. There are significant relationships between numerous reintegration variables and emotional state following release. At each postrelease point, lower depression and anxiety among participants were related to higher age and improved psychological health. Higher depression and anxiety were related to participation in a postrelease program. Theoretical implications for reintegration theory are discussed, together with practical applications.
Global Inequality, Human Rights and Power: A Critique of Ulrich Beck's Cosmopolitanism
Authors: Martell Luke
Published: March 2009

This article is a critique of Ulrich Beck's advocacy of a cosmopolitan approach to global inequality and human rights. It is argued that cosmopolitanism does not bring a new and unique perspective on global inequality. In fact Beck's proposals on migration would reinforce inequality and anti-cosmopolitanism. It is argued that his `both/and' perspective on hybridization and contextual universalism is undermined by inequality, conflict and power that are glossed over in Beck's approach. I argue that human rights interventionism as advocated by Beck falls short of cosmopolitanism, in ways which are shown by qualifications about power and inequality that Beck himself makes in his arguments.
American Reporting of School Violence and `People Like Us': A Comparison of Newspaper Coverage of the Columbine and Red Lake School Shootings
Authors: Leavy Patricia , Maloney Kathryn P.
Published: March 2009

The 1999 shootings at Columbine High School received saturation coverage by the American media. How did newspaper reporting of the 2005 Red Lake Indian Reservation School shootings, the largest school killing since Columbine, compare with the press's representations of Columbine? In this article we perform a qualitative content analysis of three newspapers ( The New York Times as the national paper of record, and local papers in the communities in which the events occurred) over a two-week period following each event. We found that the reporting of Columbine and Red Lake differed in terms of quantity, content, and form. Columbine was immediately marked with social significance and became a national story while Red Lake received significantly less coverage, mostly local. Red Lake reporting was explicitly raced and classed while the prominent role of race and gender in the Columbine killings was largely ignored by local and national media.
Infectious Disease Concepts and Considerations in the Diabetic Patient
Authors: Schwartz Michael D. , Kincaid Scott E.
Published: March 2009

Diabetic patients present their providers with unique clinical challenges when dealing with prevention and treatment of infectious diseases. By the very nature of their diabetes, these patients are at much higher risk of complications from seemingly benign infections as well as increasingly susceptible to more resistant or invasive disease. Targeted prevention where possible, regular follow-up, and early, aggressive treatment are crucial to diabetic patients’ longevity and quality of life. This review will focus on key vaccine-preventable issues as well as management of common conditions such as urinary tract infection and skin and soft tissue infection often seen in diabetic patients.
Connected Vibrating Piezoelectric Bimorph Beams as a Wide-band Piezoelectric Power Harvester
Authors: Zengtao Yang  , Jiashi Yang
Published: March 2009

We analyze coupled flexural vibration of two elastically and electrically connected piezoelectric beams near resonance for converting mechanical vibration energy to electrical energy. Each beam is a so-called piezoelectric bimorph with two layers of piezoelectrics. The 1D equations for bending of piezoelectric beams are used for a theoretical analysis. An exact analytical solution to the beam equations is obtained. Numerical results based on the solution show that the two resonances of individual beams can be tuned as close as desired by design when they are connected to yield a wide-band electrical output. Therefore, the structure can be used as a wide-band piezoelectric power harvester.
A Low-order Model for the Design of Piezoelectric Energy Harvesting Devices
Authors: Kauffman Jeffrey L. , Lesieutre George A.
Published: March 2009

Piezoelectric energy harvesting devices are an attractive approach to providing remote wireless power sources. They operate by converting available vibration energy and storing it as electrical energy. Currently, most devices rely on mechanical excitation near their resonance frequency, so a low-order model which computes a few indicators of device performance is a critical design tool. Such a model, based on the assumed modes method, develops equations of motion to provide rapid computations of key device parameters, such as the natural frequencies, mode shapes, and electro-mechanical coupling coefficients. The model is validated with a comparison of its predictions and experimental data.