bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart rate reduction by inhibition of If or by β‐blockade has different effects on postsystolic wall thickening
Authors: Lucats L , Ghaleh B , Colin P , Monnet X , Bizé A , Berdeaux A 
Published: December 2006

Background and purpose:Postsystolic wall thickening (PSWT) is part of thickening that occurs after end‐systole and represents wasted effort as it does not contribute to ejection. The effects of antianginal drugs on PSWT remain to be established. We compared the effects on PSWT of two agents that reduce heart rate, the β‐blocker atenolol and the selective inhibitor of If current, ivabradine.Experimental approach:Six dogs were prepared to measure wall thickening by sonomicrometry in the conscious state, at rest and during exercise, after administration of saline, atenolol (1mg.kg‐1) or ivabradine (1mg.kg‐1).Key results:Atenolol and ivabradine similarly reduced heart rate vs saline at rest (about 10‐20%) and during exercise (about 30%). Atenolol but not ivabradine decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest (0.35±0.07 vs 0.21±0.03mm, respectively) and during exercise (0.30±0.04 vs 0.15±0.04mm, respectively). In contrast, ivabradine did not alter PSWT. Importantly, atenolol but not ivabradine increased the ratio of postsystolic to systolic wall thickening by 80±23%. This enhanced thickening during diastole with atenolol was accompanied by impeded isovolumic relaxation of the left ventricle, as illustrated by the significant correlation between the isovolumic relaxation time constant τ and the postsystolic to systolic wall thickening ratio. None of these effects of atenolol were abolished when heart rate was controlled with atrial pacing.Conclusion and implications:For a similar heart rate reduction at rest and during exercise, ivabradine, but not atenolol, did not alter PSWT and preserved the part of thickening contributing to ejection.British Journal of Pharmacology (2007) 150, 335–341. doi:10.1038/sj.bjp.0706996
Meal Patterns, Dietary Fat Intake and Pancreatic Enzyme Use in Preadolescent Children With Cystic Fibrosis
Authors: Schall Joan I , Bentley Tyrone , Stallings Virginia A 
Published: December 2006

ABSTRACTObjectives:To describe the usual pattern of intake and adherence to cystic fibrosis (CF) food and pancreatic enzyme replacement therapy (PERT) recommendations in preadolescent children with CF and pancreatic insufficiency (PI).Methods:Children, 8 to 11 years old, with CF and PI were assessed for PERT adherence ratio (number taken/number prescribed per day) and energy and fat intake for 7 days (weighed food records), adherence to PERT and dietary recommendations, pulmonary function, growth status and stool fat malabsorption. Using the PERT adherence ratio, children were divided into good (≥80%), moderate (60% to 79%) and poor (<60%) adherence groups.Results:Of the 75 children (age, 9.3 ± 1.0 years; forced expiratory volume in 1 s, 95 ± 14% predicted), 61% consumed less than 120% of energy intake, and 72% consumed less than 40% of calories as fat recommended for CF. Using the PERT adherence ratio (mean ± SD, 75 ± 14%), 29%, 61% and 9% of children had good, moderate and poor adherence, respectively. Better adherence to PERT was significantly associated with missing fewer snacks, higher energy intake, greater fat content of snacks and poorer growth status. About 85% of the children were in the 500 to 4000 lipase unit (LU) of PERT (LU/g fat per day) and 500 to 2500 LU/kg per body weight per meal guidelines, whereas only 58% to 68% were within the guidelines for snacks. Eleven percent of children always took PERT at an inappropriate time after meals.Conclusions:Most preadolescent children with CF and PI did not meet dietary recommendations. Future educational and behavioral interventions focused on increasing PERT adherence with snacks, fat content of meals and snacks, appropriate timing of enzymes and adjustment of PERT and meal fat content are suggested.
Dietary and Circulating Polyunsaturated Fatty Acids in Cystic Fibrosis: Are They Related to Clinical Outcomes?
Authors: Colombo Carla , Bennato Veronica , Costantini Diana , Valmarana Lauretta , Daccò Valeria , Zazzeron Laura , Ghisleni Diana , Bruzzese Maria Grazia , Scaglioni Silvia , Riva Enrica , Agostoni Carlo 
Published: December 2006

ABSTRACTObjective:To assess the relationship between dietary intakes, plasma phospholipid (PL) fatty acid profile and clinical parameters in children with cystic fibrosis (CF) in comparison to healthy controls.Patients and Methods:A cross‐sectional survey including 37 patients with CF (ages 8.0 ± 2.9 yrs) and a reference group of 68 healthy children (ages 8.0 ± 0.7 yrs) was carried out by means of a food‐frequency questionnaire. At enrolment, all subjects underwent blood sampling for plasma PL fatty acids (FA). In CF patients, pulmonary function tests (forced expiratory volume in 1 second and forced vital capacity), anthropometric measurements and the Shwachman score were also determined.Results:In CF patients, mean z score for weight and height (−0.35 ± 1.16 and −0.28 ± 0.99) were lower than controls (0.83 ± 1.73 and 0.55 ± 1.11, respectively). Patients with CF showed higher energy intakes (110 ± 43 kcal/d) compared with controls (75 ± 22 kcal/d; P < 0.0001), with higher intake of total (saturated and monounsaturated) fats and lower intake of polyunsaturated FA (3.9 ± 1.0% of total macronutrient intake vs 4.3 ± 1.2%, P = 0.05). In CF patients, plasma and PL levels of linoleic and docosahexaenoic acids were lower, whereas those of arachidonic acid were similar compared with controls. The Shwachman score showed significant positive associations with plasma PL levels of arachidonic acid and total n‐6 long‐chain FA (r = 0.32, P = 0.05, and r = 0.35, P = 0.03, respectively).Conclusions:The data give suggestions that fat intake and CF‐associated biomechanisms are bound in a vicious circle, concurring to create the clinical and biochemical picture of CF. The quantity and quality of fat supplementation in CF need careful attention to balance the fat supply with polyunsaturated FA.
The Prevalence of Long Bone Fractures in Pediatric Inflammatory Bowel Disease
Authors: Persad Rabindranath , Jaffer Iqbal , Issenman Robert M 
Published: December 2006

ABSTRACTIntroduction:The association of inflammatory bowel disease (IBD) with decreased bone mineral density is well recognized. In the adult population, up to 50% of IBD patients are reported to have osteopenia, correlating with an increase in the incidence of fractures as compared with controls. The aim of this study was to determine the prevalence of fractures in a pediatric population with IBD as compared with healthy sibling controls (SC).Patients and Methods:The families of 209 patients with IBD were sent a questionnaire asking them to compare their children with IBD to a healthy sibling (non‐IBD).Results:Surveys were returned by 132 of the 209 families (63%). The sample characteristics of this sample closely resembled the overall clinic population for age (mean 14.3 vs 14.7 years), gender (53% vs 59% male) and diagnosis (58.1 vs 57.8 Crohn disease). Completed surveys described 263 children. Of the 132 with IBD 73 (55%) had Crohn disease, 52 (39%) had ulcerative colitis and 7 (6%) had indeterminate colitis. There were 76/132 males (age range, 4–18 years) with IBD and 64/131 males (age range, 1–26 years) in the sibling controls. Mean ages of the IBD sample 14.3 ±.3 was compared with 13.9 ± in SC. Of the total group, 73/263 (28%) reported ever having a fracture, 44 (60%) were siblings (SC), and 29 (40%) had IBD. Of the 29 children with IBD, 17 (59%) reported having a fracture after diagnosis including 2 who had fractures both before and after diagnosis. The total number of fractures reported was 96 (55 SC:41 IBD).Conclusion:In this survey, we found no statistically significant difference in the prevalence of fracture in IBD patients compared with their normal siblings.
Efficacy of Granulocyte Apheresis in Pediatric Patients With Ulcerative Colitis: A Pilot Study
Authors: Ikeda Hitoshi , Ishimaru Yuki , Takayasu Hajime , Fujino Junko , Kisaki Yoshiyuki , Otani Yushi , Yamagishi Junko , Tahara Kazunori 
Published: December 2006

ABSTRACTObjectives:Granulocyte apheresis (GCAP), involving the removal of granulocytes from the blood, may improve clinical symptoms and facilitate a reduction in the dose of steroids in adult patients with ulcerative colitis. As a preliminary trial, GCAP was used to taper the dose of steroids in 4 pediatric patients with ulcerative colitis.Methods:Three males and 1 female ranging from 11 to 17 years old were treated with GCAP once per week for 5 consecutive weeks/course. The ages of patients at clinical onset ranged from 8 to 12 years and the length of time from the clinical onset to GCAP treatment ranged from 28 to 58 months (median, 38.5 months).Results:In 2 patients, symptoms and signs indicating disease activity improved after 2 courses of GCAP. Laboratory data and endoscopic findings also improved after treatment and the clinical efficacy was judged to be excellent in these patients. In 1 patient, GCAP improved laboratory and endoscopic hallmarks, but bloody stools persisted. Finally, the treatment was ineffective in the fourth patient who eventually underwent surgery.Conclusions:GCAP is effective in improving clinical symptoms and may play an important role in converting steroid therapy to other treatments in children with steroid‐refractory or steroid‐dependent ulcerative colitis.
Novel Transcription Factors Are Induced by Chronic Cocaine Treatment
Authors: HOPE BRUCE T. 
Published: December 2006

SUMMARYThere are many other transcription factors that are regulated by cocaine, and there are several nontranscriptional mechanisms of regulating protein levels as well. However, the induction of the chronic AP‐1 complex and the chronic Fras provides a mechanism capable of underlying long‐lasting alterations in gene expression following chronic cocaine treatment. We hypothesize that while the well‐known acute effects of cocaine are occurring, the acutely induced cAMP pathway, possibly in conjunction with other second messenger pathways, is also inducing two general types of alterations in gene expression. 1. Acutely induced significant alterations in gene expression are rapidly induced and relatively short‐lived. These alterations in gene expression would allow the cell to rapidly adapt to cocaine in its environment without committing to long‐term changes. 2. Additional alterations in gene expression are induced by each acute administration during chronic cocaine exposure. These latter alterations are gradually induced and long‐lasting. With each acute activation, the level of induction of these latter longer‐lasting alterations in gene expression would be relatively small and insignificant compared to the rapidly induced acute alterations in gene expression. Therefore, with each acute administration, the cell does not commit itself to long‐term alterations. However, these small but longer lasting changes in gene expression would accumulate with each acute administration during chronic cocaine treatment, similar to the accumulation of the chronic AP‐1 complex (Fig. 4). The cumulative alterations which occur during repeated administrations eventually reach a level where they produce significant and long‐lasting alterations in gene expression different from those induced acutely. This incremental induction of long‐lasting alterations in gene expression would allow the cell to gradually commit to long‐term alterations for the purpose of adapting to repeated long‐term exposure to cocaine in its environment. These long‐lasting alterations in gene expression may underlie the gradual induction of persistent changes in protein levels, neuronal signaling, and related behaviors. This hypothesis allows for the different adaptations observed following acute versus chronic cocaine administration at the biochemical, physiological, and behavioral levels.We hope these investigations provide ideas for specific pharmacological blockade or reversal of the long‐term, versus short‐term, alterations in gene expression that lead to addiction, without interfering with the animal's or human's ability to experience reward. This would be important for ensuring both efficacy and compliance.
Metrisation, Topological Groups, and Compacta
Authors: COLLINS P.J. , GARTSIDE P.M. 
Published: December 2006

ABSTRACT:The paper discusses metrisation and generalised metric space properties of topological groups and compacta, with special reference to recent work of Cairns on reflection theorems, of Cairns, Knight, and Rudin on monotone normality, and of Gartside and Rezničenko on set‐Mal'tsev operators and stratifiable topological groups.
On the Completion of a MAP Group
Authors: GALINDO JORGE , HERNÁNDEZ SALVADOR 
Published: December 2006

ABSTRACT:The following question is adressed in this paper: Given a maximally almost periodic (MAP) group, is the bilateral Rai&#x030c;ov completion of G also a MAP group?It is proved by means of an example that the answer is negative in general. Then a characterization of the MAP groups having a MAP completion is obtained so that some sufficient conditions follow from it.
A Minimal Sober Topology Is Always Scott
Authors: MCCLUSKEY A.E. , McCARTAN S.D. 
Published: December 2006

ABSTRACT:Given the lattice of all topologies definable for an infinite set X, we employ he well‐developed contraction technique (of intersecting a given topology with a suitably chosen principal ultratopology) for solving many minimality problems. We confirm its potential in characterising and, where possible, identifying those topologies which are minimal with respect to certain separation axioms, notably that of sobriety and its conjunction with various other axioms. Finally, we offer an alternative description of each topologically established minimal structure in terms of the behavior of the naturally occurring specialization order and the intrin sic topology on the resulting partially‐ordered set.
Asbestos Redirects Nitric Oxide Signaling through Rapid Catalytic Conversion to Nitrite
Authors: Thomas Douglas D. , Espey Michael G. , Pociask Derek A. , Ridnour Lisa A. , Donzelli Sonia , Wink David A. 
Published: December 2006

Abstract
Asbestos exposure is strongly associated with the development of malignant mesothelioma, yet the mechanistic basis of this observation has not been resolved. Carcinogenic transformation or tumor progression mediated by asbestos may be related to the generation of free radical species and perturbation of cell signaling and transcription factors. We report here that exposure of human mesothelioma or lung carcinoma cells to nitric oxide (NO) in the presence of crocidolite asbestos resulted in a marked decrease in intracellular nitrosation and diminished NO-induced posttranslational modifications of tumor-associated proteins (hypoxia-inducible factor-1α and p53). Crocidolite rapidly scavenged NO with concomitant conversion to nitrite (NO2−). Crocidolite also catalyzed the nitration of cellular proteins in the presence of NO2− and hydrogen peroxide. Nitrated protein adducts are a prominent feature of asbestos-induced lung injury. These data highlight the ability of asbestos to induce phenotypic cellular changes through two processes: (a) by directly reducing bioactive NO levels and preventing its subsequent interaction with target molecules and (b) by increasing oxidative damage and protein modifications through NO2 production and 3-nitrotyrosine formation. (Cancer Res 2006; 66(24): 11600-4)
G-Quadruplexes Induce Apoptosis in Tumor Cells
Authors: Qi Haiyan , Lin Chao-Po , Fu Xuan , Wood Laurence M. , Liu Angela A. , Tsai Yuan-Chin , Chen Yongjie , Barbieri Christopher M. , Pilch Daniel S. , Liu Leroy F. 
Published: December 2006

Abstract
Several G-rich oligodeoxynucleotides (ODNs), which are capable of forming G-quadruplexes, have been shown to exhibit antiproliferative activity against tumor cell lines and antitumor activity in nude mice carrying prostate and breast tumor xenografts. However, the molecular basis for their antitumor activity remains unclear. In the current study, we showed that a variety of telomeric G-tail oligodeoxynucleotides (TG-ODNs) exhibited antiproliferative activity against many tumor cells in culture. Systematic mutational analysis of the TG-ODNs suggests that the antiproliferative activity depends on the G-quadruplex conformation of these TG-ODNs. TG-ODNs were also shown to induce poly(ADP-ribose) polymerase-1 cleavage, phosphatidylserine flipping, and caspase activation, indicative of induction of apoptosis. TG-ODN–induced apoptosis was largely ataxia telangiectasia mutated (ATM) dependent. Furthermore, TG-ODN–induced apoptosis was inhibited by the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. Indeed, TG-ODNs were shown to activate the JNK pathway in an ATM-dependent manner as evidenced by elevated phosphorylation of JNK and c-Jun. Interestingly, a number of G-quadruplex ODNs (GQ-ODN) derived from nontelomeric sequences also induced ATM/JNK-dependent apoptosis, suggesting a possible common mechanism of tumor cell killing by GQ-ODNs. (Cancer Res 2006; 66(24): 11808-16)
Antitumor Effect of 2-Methoxyestradiol in a Rat Orthotopic Brain Tumor Model
Authors: Kang Seung-Hee , Cho Heidi T. , Devi Sarojini , Zhang Zhaobin , Escuin Daniel , Liang Zhongxing , Mao Hui , Brat Daniel J. , Olson Jeffrey J. , Simons Jonathan W. , LaVallee Theresa M. , Giannakakou Paraskevi , Van Meir Erwin G. , Shim Hyunsuk 
Published: December 2006

Abstract
Grade 4 malignant glioma (GBM) is a fatal disease despite aggressive surgical and adjuvant therapies. The hallmark of GBM tumors is the presence of pseudopalisading necrosis and microvascular proliferation. These tumor cells are hypoxic and express hypoxia-inducible factor-1 (HIF-1), a prosurvival transcription factor that promotes formation of neovasculature through activation of target genes, such as vascular endothelial growth factor. Here, we evaluated whether 2-methoxyestradiol, a microtubule and HIF-1 inhibitor, would have therapeutic potential for this disease in a 9L rat orthotopic gliosarcoma model using a combination of noninvasive imaging methods: magnetic resonance imaging to measure the tumor volume and bioluminescence imaging for HIF-1 activity. After imaging, histologic data were subsequently evaluated to elucidate the drug action mechanism in vivo. Treatment with 2-methoxyestradiol (60–600 mg/kg/d) resulted in a dose-dependent inhibition of tumor growth. This effect was also associated with improved tumor oxygenation as assessed by pimonidazole staining, decreased HIF-1α protein levels, and microtubule destabilization as assessed by deacetylation. Our results indicate that 2-methoxyestradiol may be a promising chemotherapeutic agent for the treatment of malignant gliomas, with significant growth inhibition. Further studies are needed to assess the effect of low or intermediate doses of 2-methoxyestradiol in combination with chemotherapeutic agents in clinical studies focused on malignant gliomas. In addition to showing tumor growth inhibition, we identified three potential surrogate biomarkers to determine the efficacy of 2-methoxyestradiol therapy: decreased HIF-1α levels, α-tubulin acetylation, and degree of hypoxia as determined by pimonidazole staining. (Cancer Res 2006; 66(24): 11991-7)
Diverse Gene Expression and DNA Methylation Profiles Correlate with Differential Adaptation of Breast Cancer Cells to the Antiestrogens Tamoxifen and Fulvestrant
Authors: Fan Meiyun , Yan Pearlly S. , Hartman-Frey Cori , Chen Lei , Paik Henry , Oyer Samuel L. , Salisbury Jonathan D. , Cheng Alfred S.L. , Li Lang , Abbosh Phillip H. , Huang Tim H-M. , Nephew Kenneth P. 
Published: December 2006

AbstractThe development of targeted therapies for antiestrogen-resistant breast cancer requires a detailed understanding of its molecular characteristics. To further elucidate the molecular events underlying acquired resistance to the antiestrogens tamoxifen and fulvestrant, we established drug-resistant sublines from a single colony of hormone-dependent breast cancer MCF7 cells. These model systems allowed us to examine the cellular and molecular changes induced by antiestrogens in the context of a uniform clonal background. Global changes in both basal and estrogen-induced gene expression profiles were determined in hormone-sensitive and hormonal-resistant sublines using Affymetrix Human Genome U133 Plus 2.0 Arrays. Changes in DNA methylation were assessed by differential methylation hybridization, a high-throughput promoter CpG island microarray analysis. By comparative studies, we found distinct gene expression and promoter DNA methylation profiles associated with acquired resistance to fulvestrant versus tamoxifen. Fulvestrant resistance was characterized by pronounced up-regulation of multiple growth-stimulatory pathways, resulting in estrogen receptor α (ERα)–independent, autocrine-regulated proliferation. Conversely, acquired resistance to tamoxifen correlated with maintenance of the ERα-positive phenotype, although receptor-mediated gene regulation was altered. Activation of growth-promoting genes, due to promoter hypomethylation, was more frequently observed in antiestrogen-resistant cells compared with gene inactivation by promoter hypermethylation, revealing an unexpected insight into the molecular changes associated with endocrine resistance. In summary, this study provides an in-depth understanding of the molecular changes specific to acquired resistance to clinically important antiestrogens. Such knowledge of resistance-associated mechanisms could allow for identification of therapy targets and strategies for resensitization to these well-established antihormonal agents. (Cancer Res 2006; 66(24): 11954–66)
RhoA Mediates Cyclooxygenase-2 Signaling to Disrupt the Formation of Adherens Junctions and Increase Cell Motility
Authors: Chang Yu-Wen E. , Marlin Jerry W. , Chance Terry W. , Jakobi Rolf 
Published: December 2006

AbstractCyclooxygenase-2 (COX-2) represents an important target for treatment and prevention of colorectal cancer. Although COX-2 signaling is implicated in promoting tumor cell growth and invasion, the molecular mechanisms that mediate these processes are largely unknown. In this study, we show that the RhoA pathway mediates COX-2 signaling to disrupt the formation of adherens junctions and increase cell motility. Disruption of adherens junctions promotes tumor cell invasion and metastasis and is often associated with tumor progression. We detected high levels of RhoA activity in HCA-7 colon carcinoma cells that constitutively express COX-2. Inhibition of COX-2 significantly reduced the levels of RhoA activity in HCA-7 cells, suggesting that constitutive expression of COX-2 stimulates RhoA activity. Interestingly, inhibition of COX-2 or silencing of COX-2 expression with small interfering RNA (siRNA) stimulated the formation of adherens junctions, concomitant with increased protein levels of E-cadherin and α-catenin. Furthermore, inhibition of RhoA or silencing of RhoA expression with siRNA increased the levels of E-cadherin and α-catenin. Inhibition of Rho kinases (ROCK), the RhoA effector proteins, also increased levels of E-cadherin and α-catenin and stimulated formation of adherens junctions. The motility of HCA-7 cells was significantly decreased when COX-2 or RhoA was inhibited. Therefore, our data reveal a novel molecular mechanism that links COX-2 signaling to disrupt the formation of adherens junctions; COX-2 stimulates the RhoA/ROCK pathway, which reduces levels of E-cadherin and α-catenin leading to disruption of adherens junction formation and increased motility. Understanding of COX-2 downstream signaling pathways that promote tumor progression is crucial for the development of novel therapeutic strategies. (Cancer Res 2006; 66(24): 11700-8)