bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation and expression analyses of the MET and CDKN2A genes in rhabdomyosarcoma with emphasis on MET overexpression
Authors: Chen Yuyan , Takita Junko , Mizuguchi Masashi , Tanaka Kiyoshi , Ida Kohmei , Koh Katsuyoshi , Igarashi Takashi , Hanada Ryoji , Tanaka Yukichi , Park Myoung‐Ja , Hayashi Yasuhide 
Published: January 2007

AbstractRhabdomyosarcoma (RMS) is the most common soft‐tissue sarcoma of childhood. The simultaneous loss of Ink4a/Arf function and disruption of Met signaling in Ink4a/Arf−/− mice transgenic for hepatocyte growth factor/scatter factor (HGF/SF) induces RMS with extremely high penetrance and short latency. To address the roles of MET and CDKN2A (p16INK4A/p14ARF) in human RMS, we performed mutational analyses in 39 samples of RMS by PCR‐SSCP. No mutations were detected in exons 14–21 of MET whereas a nonsense mutation at codon 80 of p16INK4A was identified in an alveolar RMS cell line. We also quantified the relative expression levels and DNA copy numbers of these genes in seven cell lines and 17 fresh tumors by real‐time quantitative PCR. Expression of MET was detected in all samples; however, more than 10‐fold difference was found in the samples with higher or lower expression level, despite a normal DNA copy number. The protein expression level was consistent with that of mRNA, and in cell lines with a higher expression level, MET was constitutively activated. Notably, the expression level of MET was significantly higher in patients who died (P = 0.02), in patients with stage IV (P = 0.04), as well as in patients with PAX3‐FKHR chimeric transcript (P = 0.04). On the other hand, reduced or absent expression of p16INK4A and/or p14ARF showed no significant correlation with the clinicopathological parameters, except for the age at diagnosis. Our data suggest that MET plays a role in the progression of RMS. © 2007 Wiley‐Liss, Inc.
Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: Identification of candidate amplified and overexpressed genes
Authors: Narayan Gopeshwar , Bourdon Veronique , Chaganti Seeta , Arias‐Pulido Hugo , Nandula Subhadra V. , Rao Pulivarthi H. , Gissmann Lutz , Dürst Matthias , Schneider Achim , Pothuri Bhavana , Mansukhani Mahesh , Basso Katia , Chaganti R. S. K. , Murty Vundavalli V. 
Published: January 2007

AbstractCervical cancer (CC) cells exhibit complex karyotypic alterations, which is consistent with deregulation of numerous critical genes in its formation and progression. To characterize this karyotypic complexity at the molecular level, we used cDNA array comparative genomic hybridization (aCGH) to analyze 29 CC cases and identified a number of over represented and deleted genes. The aCGH analysis revealed at least 17 recurrent amplicons and six common regions of deletions. These regions contain several known tumor‐associated genes, such as those involved in transcription, apoptosis, cytoskeletal remodeling, ion‐transport, drug metabolism, and immune response. Using the fluorescence in situ hybridization (FISH) approach we demonstrated the presence of high‐level amplifications at the 8q24.3, 11q22.2, and 20q13 regions in CC cell lines. To identify amplification‐associated genes that correspond to focal amplicons, we examined one or more genes in each of the 17 amplicons by Affymetrix U133A expression arrays and semiquantitative reverse‐transcription PCR (RT‐PCR) in 31 CC tumors. This analysis exhibited frequent and robust upregulated expression in CC relative to normal cervix for genes EPHB2 (1p36), CDCA8 (1p34.3), AIM2 (1q22‐23), RFC4, MUC4, and HRASLS (3q27‐29), SKP2 (5p12‐13), CENTD3 (5q31.3), PTK2, RECQL4 (8q24), MMP1 and MMP13 (11q22.2), AKT1 (14q32.3), ABCC3 (17q21‐22), SMARCA4 (19p13.3) LIG1 (19q13.3), UBE2C (20q13.1), SMC1L1 (Xp11), KIF4A (Xq12), TMSNB (Xq22), and CSAG2 (Xq28). Thus, the gene dosage and expression profiles generated here have enabled the identification of focal amplicons characteristic for the CC genome and facilitated the validation of relevant genes in these amplicons. These data, thus, form an important step toward the identification of biologically relevant genes in CC pathogenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2007 Wiley‐Liss, Inc.
In search of a corrected prescription drug Elasticity estimate: a meta‐regression approach
Authors: Gemmill Marin C. , Costa‐Font Joan , McGuire Alistair 
Published: January 2007

AbstractAn understanding of the relationship between cost sharing and drug consumption depends on consistent and unbiased price elasticity estimates. However, there is wide heterogeneity among studies, which constrains the applicability of elasticity estimates for empirical purposes and policy simulation. This paper attempts to provide a corrected measure of the drug price elasticity by employing meta‐regression analysis (MRA). The results indicate that the elasticity estimates are significantly different from zero, and the corrected elasticity is −0.209 when the results are made robust to heteroskedasticity and clustering of observations. Elasticity values are higher when the study was published in an economic journal, when the study employed a greater number of observations, and when the study used aggregate data. Elasticity estimates are lower when the institutional setting was a tax‐based health insurance system. Copyright © 2007 John Wiley & Sons, Ltd.
Do health expenditures ‘catch‐up’? Evidence from OECD countries
Authors: Narayan Paresh Kumar 
Published: January 2007

AbstractIn this paper, we examine the ‘catch‐up’ hypothesis, that is, whether or not per capita health expenditures of the UK, Canada, Japan, Switzerland, and Spain converge to the per capita health expenditures of the USA over the period 1960–2000. We propose a framework to examine convergence of health expenditures and use recent developments in unit root testing, namely the Lagrange multiplier univariate and panel approaches that allow for at most two structural breaks. Our main finding is that while univariate and panel tests that do not incorporate structural breaks fail to find evidence of convergence, univariate and panel LM tests that allow for structural breaks find strong evidence of convergence of per capita health expenditures of the UK, Canada, Japan, Switzerland, and Spain to that of the USA. Copyright © 2007 John Wiley & Sons, Ltd.
The effects of income, education and age on health
Authors: Kiuila Olga , Mieszkowski Peter 
Published: January 2007

AbstractWe use the core interviews of the US Health Interview Survey for the years 1987–1994, to study the effects of socioeconomic status (SES) on mortality and self‐reported health. We find, consistent with previous studies, that the relationship between mortality and indicators such as education and income diminishes with age. We consider new explanations for this result and conclude that general biological deterioration at old age is probably the principal one. One important piece of evidence for this conclusion is the finding that there is no relationship at all between mortality and SES for people whose self‐reported health status at baseline is either fair or poor. Copyright © 2007 John Wiley & Sons, Ltd.
Activity‐based financing of health care––experiences from Sweden
Authors: Kastberg Gustaf , Siverbo Sven 
Published: January 2007

AbstractThe market‐inspired control models that go under the name of New Public Management (NPM) are no longer being debated in the arena of public health care as they once were, although there are still very clear signs of NPM in many countries. One manifestation of NPM in health care is activity‐based financing. The first purpose of this paper is to describe what impacts activity‐based financing has had in Sweden's public health service. The second purpose is to explain why the application of the payment model has been gradually changed. The basis for the paper comprises research done on activity‐based financing. The review of the development within Swedish health care regarding activity‐based financing shows that effects appear. But it also becomes evident that the models often are adjusted and that the adjustments, for example the introduction of a production ceiling, changes the effects. The fundamental dilemma appears to be finding a balance between production efficiency and total cost control. Copyright © 2007 John Wiley & Sons, Ltd.
LIF‐immobilized nonwoven polyester fabrics for cultivation of murine embryonic stem cells
Authors: Çetinkaya Gaye , Türkoğlu Hilal , Arat Sezen , Odaman Hande , Onur Mehmet A. , Gümüşderelioğlu Menemşe , Tümer Aşkın 
Published: January 2007

AbstractEmbryonic stem (ES) cells have a great interest for tissue engineering because of their pluripotent nature and proliferative capacity. The objective of this study is to constitute a synthetic microenvironment to support the in vitro propagation of murine ES cells in an undifferentiated state. That is why we used a three‐dimensional matrix, nonwoven polyester fabric (NWPF), which was formed from poly(ethylene terephthalate) (PET) fibers. NWPF discs were partially hydrolyzed, and then the carboxyl groups were coupled with leukemia inhibitory factor (LIF) in the presence of water‐soluble carbodiimide. The effectiveness of immobilization process was checked with ATR‐FTIR spectroscopy, fluorimetry, and cell culture studies. ES cell colony morphology, alkaline phosphatase (AP) activity, stage‐specific embryonic antigen‐1 (SSEA‐1) immunoreactivity, and SEM analysis following a 72–96‐h culture period upon hydrolyzed and LIF‐immobilized surfaces were assessed to determine the pluripotent status of ES cells. Results revealed that LIF was active in immobilized form; undifferentiated colonies had not only a significant AP and SSEA‐1 immunoreactivity, but also a higher undifferentiated colony ratio on LIF‐immobilized surfaces than that of hydrolyzed surfaces. The immobilized LIF protein might be a good model to provide a feeder‐free system, but the physical properties of the scaffold is more convenient for differentiation studies. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.
TLR3 signaling in a hepatoma cell line is skewed towards apoptosis
Authors: Khvalevsky Elina , Rivkin Ludmila , Rachmilewitz Jacob , Galun Eithan , Giladi Hilla 
Published: January 2007

AbstractToll‐like receptors (TLRs) recognize pathogen‐associated molecular patterns (PAMPS) leading to the activation of the innate immune response and subsequently to the shaping of the adaptive immune response. Of the known human TLRs, TLR3, 7, 8, and 9 were shown to recognize nucleic acid ligands. TLR3 signaling is induced by double‐stranded (ds)RNA, a molecular signature of viruses, and is mediated by the TRIF (TIR domain‐containing adaptor‐inducing IFNβ) adaptor molecule. Thus, TLR3 plays an important role in the host response to viral infections. The liver is constantly exposed to a large variety of foreign substances, including pathogens such as HBV (hepatitis B virus) and HCV (hepatitis C virus), which frequently establish persistent liver infections. In this work, we investigated the expression and signaling pathway of TLR3 in different hepatoma cell lines. We show that hepatocyte lineage cells express relatively low levels of TLR3 mRNA. TLR3 signaling in HEK293 cells (human embryonic kidney cells) activated NF‐κB and IRF3 (interferon regulatory factor 3) and induced IFNβ (interferon β) promoter expression, which are known to lead to pro‐inflammatory cytokine secretion. In Huh7 cells, there was only a short‐term IRF3 activation, and a very low level of IFNβ expression. In HepG2 cells on the other hand, while no induction of pro‐inflammatory factors was observed, signaling by TLR3 was skewed towards the induction of apoptosis. These results indicate preferential induction of the apoptotic pathway over the cytokine induction pathway by TLR3 signaling in hepatocellular carcinoma cells with potential implications for therapeutic strategies. J. Cell. Biochem. 100: 1301–1312, 2007. © 2007 Wiley‐Liss, Inc.
Enhanced tight junction function in human breast cancer cells by antioxidant, selenium and polyunsaturated lipid
Authors: Martin Tracey A. , Das Tapas , Mansel Robert E. , Jiang Wen G. 
Published: January 2007

AbstractParacellular permeability (PCP) is governed by tight junctions (TJs) in epithelial cells, acting as cell–cell adhesion structures, the aberration of which is known to be linked to the dissociation and metastasis of breast cancer cells. This study hypothesized that the function of TJs in human breast cancer cells can be augmented by gamma linolenic acid (GLA), selenium (Se), and iodine (I) in the presence of 17‐β‐estradiol, as these molecules are known to increase TJ functions in endothelial cells, using assays of trans‐epithelial resistance (TER), PCP, immunofluorescence, and in vitro invasion and motility models. GLA, I, and Se individually increased TER of MDA‐MB‐231 and MCF‐7 human breast cancer cells. The combination of all three agents also had a significant increase in TER. Addition of GLA/Se/I reduced PCP of both breast cancer cell lines. GLA/Se/I reversed the effect of 17‐β‐estradiol (reduced TER, increased PCP). Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h, there was increasing relocation to breast cancer cell–cell junctions of occludin and ZO‐1 in MCF‐7 cells. Moreover, treatment with GLA/Se/I, alone or in combination, significantly reduced in vitro invasion of MDA‐MB‐231 cells through an endothelial cell barrier (P < 0.0001) and reduced 17‐β‐estradiol induced breast cancer cell motility (P < 0.0001). Our previous work has demonstrated that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells; this has now proved to be true of human breast cancer cells. This combination also completely reversed the effect of 17‐β‐estradiol in these cells. J. Cell. Biochem. 101: 155–166, 2007. © 2007 Wiley‐Liss, Inc.
L‐type calcium channels in growth plate chondrocytes participate in endochondral ossification
Authors: Mancilla Edna E. , Galindo Mario , Fertilio Barbara , Herrera Mario , Salas Karime , Gatica Hector , Goecke Annelise 
Published: January 2007

AbstractLongitudinal bone growth occurs by a process called endochondral ossification that includes chondrocyte proliferation, differentiation, and apoptosis. Recent studies have suggested a regulatory role for intracellular Ca2+ (Ca) in this process. Indirect studies, using Ca2+ channel blockers and measurement of Ca, have provided evidence for the existence of Ca2+ channels in growth plate chondrocytes. Furthermore, voltage‐gated Ca2+ channels (VGCC), and specifically L‐ and T‐type VGCCs, have been recently described in murine embryonic growth plates. Our aim was to assess the effect of L‐type Ca2+ channel blockers on endochondral ossification in an organ culture. We used cultures of fetal rat metatarsal rudiments at 20 days post gestational age, with the addition of the L‐type Ca2+ channel blockers verapamil (10–100 µM) or diltiazem (10–200 µM) to the culture medium. Longitudinal bone growth, chondrocyte differentiation (number of hypertrophic chondrocytes), and cell proliferation (incorporation of tritiated thymidine) were measured. Verapamil dose‐dependently decreased growth, the number of hypertrophic chondrocytes, and cell proliferation, at concentrations of 10–100 µM. Growth and the number of hypertrophic chondrocytes decreased significantly with diltiazem at 50–100 µM, and proliferation decreased significantly at concentrations of 10–200 µM. Additionally, there was no increase in apoptosis over physiological levels with either drug. We confirmed the presence of L‐type VGCCs in rat rudiments using immunohistochemistry, and showed that the antagonists did not alter the pattern of VGCC expression. In conclusion, our data suggest that L‐type Ca2+ channel activity in growth plate chondrocytes is necessary for normal longitudinal growth, participating in chondrocyte proliferation and differentiation. J. Cell. Biochem. 101: 389–398, 2007. © 2007 Wiley‐Liss, Inc.
Mechanisms of metastasis: Epithelial‐to‐mesenchymal transition and contribution of tumor microenvironment
Authors: Tse Joyce C. , Kalluri Raghu 
Published: January 2007

AbstractEvery year about 500,000 people in the United States die as a result of cancer. Among them, 90% exhibit systemic disease with metastasis. Considering this high rate of incidence and mortality, it is critical to understand the mechanisms behind metastasis and identify new targets for therapy. In recent years, two broad mechanisms for metastasis have received significant attention: epithelial‐to‐mesenchymal transition (EMT) and tumor microenvironment interactions. EMT is believed to be a major mechanism by which cancer cells become migratory and invasive. Various cancer cells—both in vivo and in vitro—demonstrate features of epithelial‐to‐mesenchymal‐like transition. In addition, many steps of metastasis are influenced by host contributions from the tumor microenvironment, which help determine the course and severity of metastasis. Here we evaluate the diverse mechanisms of EMT and tumor microenvironment interactions in the progression of cancer, and construct a rational argument for targeting these pathways to control metastasis. J. Cell. Biochem. 101: 816–829, 2007. © 2007 Wiley‐Liss, Inc.
Effects of quercetin and quercetin 3‐glucuronide on the expression of bone sialoprotein gene
Authors: Kim Dong‐Soon , Takai Hideki , Arai Masato , Araki Shouta , Mezawa Masaru , Kawai Yoshichika , Murota Kaeko , Terao Junji , Ogata Yorimasa 
Published: January 2007

AbstractQuercetin is a typical flavonol‐type flavonoid and is present in a variety of vegetables, and their antioxidant effect implies their possible role in the prevention of oxidative stress related chronic diseases. Bone sialoprotein (BSP) is a noncollagenous protein of the extracellular matrix in the mineralized connective tissues that has been implicated in the nucleation of hydroxyapatite crystals. Previously, we reported that isoflavone (genistein) activated BSP gene transcription is mediated through an inverted CCAAT box in the proximal BSP gene promoter. The present study investigates the regulation of BSP transcription in a rat osteoblast‐like cell line, ROS 17/2.8 cells, by quercetin and its conjugated metabolite quercetin 3‐glucuronide. Quercetin and quercetin 3‐glucuronide (5 µM) increased the BSP mRNA levels at 12 h and quercetin upregulated the Cbfa1/Runx2 mRNA expression at 12 h. From transient transfection assays using various sized BSP promoter‐luciferase constructs, quercetin increased the luciferase activity of the construct (pLUC3), including the promoter sequence nucleotides −116 to −43. Transcriptional stimulations by quercetin were almost completely abrogated in the constructs that included 2 bp mutations in the inverted CCAAT and FRE elements whereas the CCAAT‐protein complex did not change after stimulation by quercetin according to gel shift assays. Quercetin increased the nuclear protein binding to the FRE and 3′‐FRE. These data suggest that quercetin and quercetin 3‐glucuronide increased the BSP mRNA expression, and that the inverted CCAAT and FRE elements in the promoter of the BSP gene are required for quercetin induced BSP transcription. J. Cell. Biochem. 101: 790–800, 2007. © 2007 Wiley‐Liss, Inc.
Metabolic syndrome and mitochondrial function: Molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function
Authors: Nicolson Garth L. 
Published: January 2007

AbstractMetabolic syndrome consists of a cluster of metabolic conditions, such as hypertriglyeridemia, hyper‐low‐density lipoproteins, hypo‐high‐density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that—in combination with genetic susceptibility and abdominal obesity—are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart disease. One of the defects in metabolic syndrome and its associated diseases is excess cellular oxidative stress (mediated by reactive oxygen and nitrogen species, ROS/RNS) and oxidative damage to mitochondrial components, resulting in reduced efficiency of the electron transport chain. Recent evidence indicates that reduced mitochondrial function caused by ROS/RNS membrane oxidation is related to fatigue, a common complaint of MS patients. Lipid replacement therapy (LRT) administered as a nutritional supplement with antioxidants can prevent excess oxidative membrane damage, restore mitochondrial and other cellular membrane functions and reduce fatigue. Recent clinical trials have shown the benefit of LRT plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Thus LRT plus antioxidant supplements should be considered for metabolic syndrome patients who suffer to various degrees from fatigue. J. Cell. Biochem. 100: 1352–1369, 2007. © 2007 Wiley‐Liss, Inc.
Rapid preparation of [11C]flumazenil: captive solvent synthesis combined with purification by analytical sized columns
Authors: Cleij Marcel C. , Clark John C. , Baron Jean‐Claude , Aigbirhio Franklin I. 
Published: January 2007

AbstractTo produce the radioligand [N‐methyl‐11C]flumazenil at very high specific radioactivity for our small animal imaging studies we have developed procedures for its rapid synthesis, purification and analysis. We have developed ‘micro‐reactor’ apparatus which are assembled from analytical HPLC guard columns packed with stainless steel powder for performing the carbon‐11 methylation reactions. These highly efficient reaction columns enable high radiochemical yields to be obtained with very small amounts of precursor (20–40 µg). The very small amount of reactants used enables the use of small analytical‐sized HPLC columns for the rapid purification of the radioligand. Combining these techniques has enabled us to consistently prepare [N‐methyl‐11C]flumazenil from [11C]iodomethane with radiochemical yields of 80% (decay corrected). This results in 8–10 GBq of [N‐methyl‐11C]flumazenil at very high specific radioactivities of 520–600 GBq/µmol at the end‐of‐synthesis. The total preparation time from end‐of‐bombardment of cyclotron‐produced [11C]carbon dioxide to end‐of‐synthesis is 20 min. A quality control method based on very rapid HPLC analysis (completed within 2 min) on a micro‐analytical HPLC column has also being developed to reduce the time from the end‐of‐synthesis to injection for imaging. Copyright © 2007 John Wiley & Sons, Ltd.
Technetium‐99m labeling and freeze‐dried kit formulation of levofloxacin (L‐Flox): a novel agent for detecting sites of infection
Authors: El‐ghany E. A. , Amin A. M. , El‐kawy O. A. , Amin Magdy 
Published: January 2007

AbstractIn this study, the labeling method of levofloxacin with technetium‐99m and its biological evaluation were described. 99mTc‐L‐Flox was synthesized via direct complexation with technetium‐99m in the presence of stannous chloride dihydrate as reducing agent. The optimum amounts of the reactants are: 1–2 mg levofloxacin, 150 µg stannous chloride dihydrate and 48–1490 MBq pertechnetate. The reaction mixture was bring to pH 6 and kept at room temperature for 30 min. The labeled levofloxacin was stable for more than 8 h. The in vivo evaluation of 99mTc‐L‐Flox in man‐induced inflammation models showed that this tracer was localized with different values. The live E. Coli model had the highest value which was 2.9%, the heat killed E. coli model had a value of 2.0%, and the turpentine oil model had a value of 1.2% at 24 post injection, while the non‐inflamed muscle had activity of 0.5%. All the gathered biological data support the usefulness of 99mTc‐L‐Flox as infection imaging agent. The freeze‐dried form of Sn‐L‐Flox was prepared and found meet all the radiochemical and biological tests. Copyright © 2007 John Wiley & Sons, Ltd.