bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Gene Expression and Cell-Cycle Signaling Pathways by the EGFR Inhibitor Gefitinib (Iressa) in Rat Urinary Bladder Cancer
Authors: Lu Yan , Liu Pengyuan , Van den Bergh Francoise , Zellmer Victoria , James Michael , Wen Weidong , Grubbs Clinton J. , Lubet Ronald A. , You Ming 
Published: October 2011

AbstractThe epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 × 10−15 (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 × 10−42 (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 × 10−8 and r = 0.73, P = 1.50 × 10−65, respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. Cancer Prev Res; 5(2); 248–59. ©2011 AACR.
Association of Known Loci With Lipid Levels Among Children and Prediction of Dyslipidemia in Adults
Authors: Tikkanen Emmi , Tuovinen Tarja , Widén Elisabeth , Lehtimäki Terho , Viikari Jorma , Kähönen Mika , Peltonen Leena , Raitakari Olli T. , Ripatti Samuli 
Published: October 2011

Background—
Recent genome-wide association studies have found 95 distinct genetic loci associated with high-density (HDL-C) and low-density (LDL-C) lipoprotein cholesterol, total cholesterol (TC), and triglycerides (TG), using adult samples. It is not known if these variants are associated with lipid levels in children and adolescents and if the genetic risk score (GRS), based on these variants, could improve adulthood dyslipidemia prediction over the childhood lipid measurements.

Methods and Results—

We used 2443 participants of the Cardiovascular Risk in Young Finns study cohort with up to 5 measurements of serum lipids taken between ages 3 and 45 years to estimate the effect of individual single-nucleotide polymorphisms and the GRS on lipids. The GRSs were strongly associated with lipids in all age groups (1.5×10
−20
<
P
<8.7×10
−12
for HDL-C, 3.5×10
−27
<
P
<5.6×10
−09
for LDL-C, 2.0×10
−25
<
P
<5.2×10
−09
for TC, and 4.1×10
−20
<
P
<8.4×10
−05
for TG). Jointly, the lipid loci explained 11.8–26.7% of the total variance in lipids among 3- to 6-year-old children, and the proportion dropped over age, except for TG. The discrimination of adult hypertriglyceridemia improved when GRS was added to childhood lipid measurement (
C
statistic=0.04,
P
=0.01).

Conclusions—
Previously identified lipid loci are associated with lipid levels in children and adolescents and explain up to more than 2 times of the lipid variation in children compared with adults. The TG-GRS improves the risk discrimination over childhood lipid measurement for adult hypertriglyceridemia.
Resistance exercise in cardiac rehabilitation
Authors: Wise Frances M , Patrick Jennifer M 
Published: October 2011

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is ‘The trainee consistently demonstrates a knowledge of basic exercise physiology and is able to advise individuals about the risks and benefits of specific exercise programmes.’ Cardiovascular disease is the leading cause of death in developed nations, and there is a clear link with physical inactivity. The benefits of resistance training in patients with coronary heart disease are well documented and can contribute to secondary prevention of heart disease with corresponding improvements in patient survival. This review describes the benefits of resistance exercise for cardiac patients, details of its prescription in this group, and considers safety and contraindications.
Left Clouds Over Climate Change Policy
Authors: Hahnel Robin 
Published: October 2011

Will there be an international climate treaty to follow Kyoto when it expires in 2012, and if so what will it look like? Many climate justice and anti-capitalist spokespersons denounce the Kyoto Protocol as a “pretend solution” and reject international carbon trading altogether. This article argues that, on the contrary, an international cap and trade treaty is the only way to avert climate change fairly before it is too late, and that the Kyoto Protocol is a framework that progressives should defend and fix rather than condemn and nix. After explaining why many climate justice and anti-capitalist criticisms of carbon trading are without merit and fail to appreciate how international carbon trading can favor lesser developed countries (LDCs), five changes to make a post-Kyoto cap and trade treaty more effective and fair are proposed, and common arguments against carbon trading are rebutted. JEL codes: Q54, Q56, Q58
Immigrants across the U.S. Federal Laboratory: Explaining State-Level Innovation in Immigration Policy
Authors: Boushey Graeme , Luedtke Adam 
Published: October 2011

AbstractThe passage of a restrictive immigration law in Arizona in 2010 rekindled an old debate in the United States on immigration policy and the role of federalism. Despite periodic constitutional controversies, scholars of federalism and U.S. state politics have not adequately explained variation in state-level policy making on immigration. The authors explore pressures leading to state immigration policy innovation and adoption in the United States. The article evaluates factors leading to the introduction and adoption of two types of policies: those dictating the cultural and economic incorporation of immigrants and those attempting to control their flow and settlement. Factors such as fiscal federalism, ethnic contact, and ethnic threat generate incentives for states to pass such laws. The authors compiled a comprehensive data set of state immigration laws from the past decade to explain how factors commonly associated with national immigration policy development—economic conditions, rates of immigration, demographics, party control, and political institutions—influence state-level immigration policy activity.
Compliance of children in northern France with physical activity recommendations
Authors: Apété Geoffroy K , Zitouni Djamel , Hubert Hervé , Guinhouya Benjamin C 
Published: October 2011

Aims: This study examined the compliance of French children with physical activity (PA) guidelines, using objective assessments of PA. Methods: The study involved 252 children aged 9.9 ± 0.9 years, with mean height and weight of 1.39 ± 0.08 m and 35.8 ± 8.8 kg, respectively. Their usual PA was evaluated during a week using an Actigraph accelerometer. Results: The time spent in a moderate-to-vigorous PA (MVPA) ranged from 142 ± 44 min.d-1 to 25 ± 18 min/day according to the cut-offs used. Boys were significantly more active than girls ( p ≤ .001). Overweight/obese children spent significantly less time in MVPA as determined with cut-off points at 3200 cpm (-26%) or 3600 cpm (-35%) ( p < .01). Between 5% (8% of boys vs 1% of girls, p < .0001) and 9% (14% of boys vs 3% of girls, p < .0001) of children probably met the PA guidelines. No relationships were found with socioeconomic status. Conclusions: This high proportion of insufficiently active children (> 90%), together with the relatively high proportion of overweight children in this area, advocates a more aggressive PA promotion project, which should target all children whatever their social origins.
TACI deficiency impairs sustained Blimp-1 expression in B cells decreasing long-lived plasma cells in the bone marrow
Authors: Tsuji Shoichiro , Cortesão Catarina , Bram Richard J. , Platt Jeffrey L. , Cascalho Marilia 
Published: October 2011

AbstractDeficiencies in transmembrane activator and CAML interactor (TACI) result in common variable immune deficiency, a syndrome marked by recurrent infections with encapsulated microorganisms, impaired production of antibodies, and lymphoproliferation. How TACI promotes antibody production and inhibits lymphoproliferation is not understood. To answer this question, we studied the generation of immunity to protein antigens in both TACI-deficient and TACI-proficient mice. We show that TACI promotes sustained Blimp-1 expression by B cells responding to antigen, which in turn limits B-cell clonal expansion and facilitates differentiation of long-lived antibody-secreting cells. Short-term IgG secretion occurs independently of TACI as DNA double-strand breaks associated with isotype class switching induce Blimp-1 transiently, independently of TACI. Our results showing that TACI induces and maintains Blimp-1 provide, for the first time, a unified molecular and cellular mechanism explaining the primary features of common variable immune deficiency, exquisite vulnerability to infection with encapsulated organisms, lymphoproliferation, and hypogammaglobulinemia.
Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma
Authors: Louis Chrystal U. , Savoldo Barbara , Dotti Gianpietro , Pule Martin , Yvon Eric , Myers G. Doug , Rossig Claudia , Russell Heidi V. , Diouf Oumar , Liu Enli , Liu Hao , Wu Meng-Fen , Gee Adrian P. , Mei Zhuyong , Rooney Cliona M. , Heslop Helen E. , Brenner Malcolm K. 
Published: October 2011

Abstract
We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBV-CTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the long-term clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome. We observed persistence for up to 192 weeks for CAR-ATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4+ cells and central memory cells (CD45RO+CD62L+) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #NCT00085930.
Lung glutathione adaptive responses to cigarette smoke exposure
Authors: Gould Neal S , Min Elysia , Gauthier Steve , Martin Richard J , Day Brian J 
Published: October 2011

Abstract

Background
Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease. A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS). Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants. The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice.

Methods
Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h. GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues. GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL) activity in lung and liver tissue.

Results
GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged. Next, the time course of rebound in GSH levels after the CS exposure was examined. CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months. Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis. Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels.

Conclusions
CS exposures evoke a powerful GSH adaptive response in the lung and systemically. These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels. Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD.
Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection
Authors: Orduña Patricia , Cevallos Miguel A , de León Samuel Ponce , Arvizu Adriana , Hernández-González Ismael L , Mendoza-Hernández Guillermo , López-Vidal Yolanda 
Published: October 2011

Abstract

Background
Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico.

Results
BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks R egion of D ifference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests.

Conclusions
BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time.
Hybrid methods for accretive variational inequalities involving pseudocontractions in Banach spaces
Authors: Wang Yaqin , Chen Rudong 
Published: October 2011

AbstractWe use strongly pseudocontractions to regularize a class of accretive variational inequalities in Banach spaces, where the accretive operators are complements of pseudocontractions and the solutions are sought in the set of fixed points of another pseudocontraction. In this paper, we consider an implicit scheme that can be used to find a solution of a class of accretive variational inequalities.Our results improve and generalize some recent results of Yao et al. (Fixed Point Theory Appl, doi:10.1155/2011/180534, 2011) and Lu et al. (Nonlinear Anal, 71(3-4), 1032-1041, 2009).2000 Mathematics subject classification 47H05; 47H09; 65J15
Toll-like receptors in cerebral ischemic inflammatory injury
Authors: Wang Yan-Chun , Lin Sen , Yang Qing-Wu 
Published: October 2011

AbstractCerebral ischemia triggers acute inflammation, which has been associated with an increase in brain damage. The mechanisms that regulate the inflammatory response after cerebral ischemia are multifaceted. An important component of this response is the activation of the innate immune system. However, details of the role of the innate immune system within the complex array of mechanisms in cerebral ischemia remain unclear. There have been recent great strides in our understanding of the innate immune system, particularly in regard to the signaling mechanisms of Toll-like receptors (TLRs), whose primary role is the initial activation of immune cell responses. So far, few studies have examined the role of TLRs in cerebral ischemia. However, work with experimental models of ischemia suggests that TLRs are involved in the enhancement of cell damage following ischemia, and their absence is associated with lower infarct volumes. It may be possible that therapeutic targets could be designed to modulate activities of the innate immune system that would attenuate cerebral brain damage. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Interpreting the molecular mechanism of ischemic tolerance will open investigative avenues into the treatment of cerebral ischemia. In this review, we discuss the critical role of TLRs in mediating cerebral ischemic injury. We also summarize evidence demonstrating that cerebral preconditioning downregulates pro-inflammatory TLR signaling, thus reducing the inflammation that exacerbates ischemic brain injury.
Changes in met perceived need for mental healthcare in Australia from 1997 to 2007
Authors: Meadows Graham N. , Bobevski Irene 
Published: October 2011

BackgroundThe Australian National Survey of Mental Health and Wellbeing conducted in 1997 and 2007 allows for exploration of changes in perceptions of mental healthcare. Major demographic, economic and health-behaviour changes have unfolded in Australia during this time. Governments also have increased spending on mental health services and been active in mental healthcare policy-making and implementation.AimsTo compare rates of meeting of perceived need for mental healthcare between these two surveys dealing with adjustable sources of error.MethodCombined data-sets from 1997 and 2007 were analysed to provide weighted population estimates. Selection, indirect standardisation to a common reference population and multinomial logistic regression were employed, addressing bias and confounding.ResultsBetween 1997 and 2007 perceived need for information, counselling and skills training among people who consulted a general practitioner, psychiatrist, or psychologist for mental health reasons has increased. Within these service users, increases in perceived responses from services are evident among people who have perceived needs for information provision and counselling.ConclusionsPolicy and service changes are among possible causal explanations. Generally, trends are in the direction that policy changes were intended to achieve, giving some encouragement that these initiatives have had some effect. Reduced unmet perceived need suggests improved access to some interventions. However, the proportion of service responses to perceived need seen as sufficient is generally unchanged. This suggests the adequacy of treatments offered, as perceived by the Australian public, may not have improved and that a continued focus on quality of care is important for the future.
Time-resolved MR angiography of the calf arteries using a phased array cardiac coil: comparison of visibility with standard three-step bolus chase MR angiography
Authors: Eshed Iris , Rimon Uri , Novikov Ilia , Goitein Orly , Konen Eli 
Published: October 2011

Background Standard bolus chase MR angiography (MRA) is increasingly replacing digital subtraction angiography (DSA) in the diagnostic evaluation of peripheral vascular disease. However, a major limitation of bolus chase MRA is the relatively poor visibility of the calf arteries. Purpose To evaluate the feasibility of visualizing the calf arteries and the visibility quality of an 8-channel cardiac phased array coil using time-resolved imaging of contrast kinetics (TRICKS) MRA compared with standard bolus chase MRA on a 1.5 Tesla MRI scanner. Material and Methods MRA findings of 59 sequential patients (mean age 57.8 years, range 14-83 years; 41 men) were retrospectively evaluated. All examinations included preliminary TRICKS for the lower leg using a surface 8-channel cardiac coil, followed by a 3-step MRA of the abdominal aorta, thigh, and lower leg using a body coil. Images yielded by both methods were separately evaluated by consensus of two radiologists unaware of the patients’ clinical data. Visibility of the calf arteries (popliteal, tibialis anterior, tibialis posterior, tibioperoneal trunk, and peroneal) for both sides was subjectively classified as ‘diagnostic’ or ‘non-diagnostic’. Descriptive statistics for image diagnostic quality were assessed. Results A total of 575 calf arterial segments were evaluated. Visibility of all calf arteries was significantly better with TRICKS than with the standard bolus chase MRA ( P < 0.001). The improvement of calf artery visibility with TRICKS was more pronounced in patients with peripheral vascular disease compared to those with arteritis, vascular malformation and popliteal entrapment syndrome. Conclusion Using a cardiac coil for MRA of the lower extremities resulted in visibility comparable to that of a dedicated leg coil, with diagnostic superiority for the TRICKS method compared to the standard bolus chase method.