tbuckley/cabot-search huggingface dataset:
Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update
Authors: Ching-Hon Pui, William L. Carroll, Soheil Meshinchi, Robert J. Arceci
Journal: Journal of Clinical Oncology (2011)

We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research.A review of English literature on childhood acute leukemias from the past 5 years was performed.Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients.The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade.
<i>RUNX3</i> Inactivation by Point Mutations and Aberrant DNA Methylation in Bladder Tumors
Authors: Wun-Jae Kim, Eun-Jung Kim, Pildu Jeong, Changyi Quan, Jiyeon Kim, Qing-Lin Li, Jeong-Ook Yang, Yoshiaki Ito, Suk-Chul Bae
Journal: Cancer Research (2005)

Abstract RUNX3 is inactivated at high frequency in many tumors. However, in most cases, inactivation is caused by silencing of the gene due to promoter hypermethylation. Because epigenetic silencing is known to affect many major tumor suppressor genes in cancer cells, it is not clear whether RUNX3 is primarily responsible for the induction of carcinogenesis in these cases, except for the gastric cancer cases that we reported previously. We investigated genetic and epigenetic alterations of RUNX3 in 124 bladder tumor cases and seven bladder tumor–derived cell lines. Here we show that RUNX3 is inactivated by aberrant DNA methylation in 73% (90 of 124) of primary bladder tumor specimens and 86% (six of seven) of bladder tumor cell lines. In contrast, the promoter regions of 20 normal bladder mucosae were unmethylated. Importantly, one patient bore missense mutations, each of which resulted in amino acid substitutions in the highly conserved Runt domain. The mutations abolished the DNA-binding ability of RUNX3. A second patient had a single nucleotide deletion within the Runt domain coding region that resulted in truncation of the protein. RUNX3 methylation was a significant risk factor for bladder tumor development, superficial bladder tumor recurrence, and subsequent tumor progression. These results strongly suggest that inactivation of RUNX3 may contribute to bladder tumor development and that promoter methylation and silencing of RUNX3 could be useful prognostic markers for both bladder tumor recurrence and progression.
Data on the Action Spectrum for Ultraviolet Carcinogenesis2
Authors: Robert G. Freeman
Journal: JNCI Journal of the National Cancer Institute (1975)

When 300, 310, or 320 nm monochromatic UV energy was given to albino mice in amounts proportional to its erythemal effectiveness, skin tumors developed on the exposed ears of the mice at approximately the same time and the same rate in all three groups. Thus the long wavelength limit of the carcinogenesis action spectrum paralleled that of the erythema action spectrum. No tumors were found in mice exposed to a 290-nm UV wavelength nor in those exposed to low dosages at 310 nm. All tumors observed in the group exposed to 300 nm were squamous cell carcinomas; 3 sarcomas and 5 squamous cell carcinomas were seen with the more penetrating doses of a 310-nm UV wavelength.
Conditions With Right Ventricular Pressure and Volume Overload, and a Small Left Ventricle: “Hypoplastic” Left Ventricle or Simply a Squashed Ventricle? 11All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.
Authors: Colin K.L. Phoon, Norman H. Silverman
Journal: Journal of the American College of Cardiology (1997)

Objectives. We modeled the utility of preoperative potential left ventricular (LV) volume in predicting postoperative volume in conditions causing LV compression. Background. With right ventricular (RV) overload lesions, LV "hypoplasia" may be primarily due to compression by reverse septal bowing. If so, preoperative potential LV volume should correspond 1:1 with postoperative volume. The potential volume for a given endocardial circumference can be calculated from the maximal potential cross-sectional area (where A = circumference2/4π) and LV length. Methods. We studied echocardiographic variables from 22 patients with RV overload lesions perioperatively. Results. Preoperative LV volume was 15.0 ± 7.1 ml/m2(59% of patients had a volume <15 ml/m2); potential volume was 20.0 ± 9.8 ml/m2. Postoperative volume increased to 28.2 ± 8.6 ml/m2(100% of patients had a volume >15 ml/m2). Preoperative potential volume correlated well with, but generally underestimated, postoperative volume (r = 0.75, p < 0.0001). Postoperative increases in both LV circumference and length contributed to this discrepancy. Conclusions. In RV overload lesions, LV "hypoplasia" is primarily due not to compression; rather it is due to underfilling. Even "hypoplastic" ventricles can achieve an adequate cavity after operation normalizes loading conditions. Both true and potential preoperative volume can predict postoperative volume well. However, potential volume, which is less prone to underestimating ventricular adequacy, may better help to determine suitability for biventricular repair in lesions of RV overload associated with a "hypoplastic" LV.
Bicarbonate (HCO3) delivery to the gastroduodenal mucosa by the blood: its importance for mucosal integrity.
Authors: M Starlinger, R Schiessel
Journal: Gut (1988)

La liberation de CO 3 H par le sang dans la muqueuse digestive est necessaire au maintien de l'integrite de la muqueuse. Au niveau de l'estomac la fonction principale de CO 3 H est probablement la regulation du pH intracellulaire et l'effusion passive apres lesion meme minime
Relation between corset use and lung function postural variation in spinal cord injury
Authors: H. Prigent, N. Roche, I. Laffont, M. Lejaille, L. Falaize, F. Barbot, F. Lofaso
Journal: European Respiratory Journal (2009)

Corsets are widely used to improve trunk stability in patients with spinal cord injury (SCI) and can improve respiratory function. The aim of the present study was to identify predictors of respiratory benefits from wearing a corset in SCI patients. In a prospective observational study, respiratory function was tested in the supine and upright seated position with and without a corset in 36 SCI patients who regularly used a corset. SCI patients who no longer used a corset were matched to users on sex, injury level and severity. Vital capacity (VC) did not differ between users and nonusers in the supine position. In users, contrary to nonusers, VC increased significantly in the supine position compared to the seated position (increase of 0.43+/-0.39 versus -0.05+/-0.32 L in nonusers; p<0.0001). Corset use was associated with a significant VC increase in the upright position (2.13+/-0.71 L without versus 2.41+/-0.69 L with the corset; p<0.001). The VC increase with the corset in the upright position correlated significantly with the VC increase induced by being supine, compared to sitting without the corset. The VC increase induced in SCI patients by lying supine may predict the effects of wearing a corset. The long-term effects of corset use should be evaluated.
Self-Help for Bulimia Nervosa: A Randomized Controlled Trial
Authors: Jacqueline C. Carter, Marion P. Olmsted, Allan S. Kaplan, Randi E. McCabe, Jennifer S. Mills, Annie Aimé
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors examined the effectiveness of unguided self-help as a first step in the treatment of bulimia nervosa. METHOD: A total of 85 women with bulimia nervosa who were on a waiting list for treatment at a hospital-based clinic participated. The patients were randomly assigned to receive one of two self-help manuals or to a waiting list control condition for 8 weeks. One of the self-help manuals addressed the specific symptoms of bulimia nervosa (cognitive behavior self-help), while the other focused on self-assertion skills (nonspecific self-help). RESULTS: Twenty patients (23.5%) dropped out of the study. The data were analyzed with intention-to-treat analysis. Although the group-by-time interaction for binge eating and purging was not statistically significant, simple effects showed that there was a significant reduction in symptom frequency in both self-help conditions at posttreatment but not in the waiting list condition. There were no statistically significant changes in levels of dietary restraint, eating concerns, concerns about shape and weight, or general psychopathology. A greater proportion of patients in the cognitive behavior self-help (53.6%) and nonspecific self-help (50.0%) conditions reported at least a 50% reduction in binge eating or purging at posttreatment, compared with the waiting list condition (31.0%). A lower baseline knowledge about eating disorders, more problems with intimacy, and higher compulsivity scores predicted a better response. CONCLUSIONS: The findings suggest that a subgroup of patients with bulimia nervosa may benefit from unguided self-help as a first step in their treatment. Cognitive behavior self-help and nonspecific self-help had equivalent effects.
LEF1 in Androgen-Independent Prostate Cancer: Regulation of Androgen Receptor Expression, Prostate Cancer Growth, and Invasion
Authors: Yirong Li, Longgui Wang, Miao Zhang, Jonathan Melamed, Xiaomei Liu, Robert Reiter, Jianjun Wei, Yi Peng, Xuanyi Zou, Angel Pellicer, Michael J. Garabedian, Anna Ferrari, Peng Lee
Journal: Cancer Research (2009)

A major obstacle in treating prostate cancer is the development of androgen-independent disease. In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate cancer growth, and invasion in androgen-independent prostate cancer cells. Affymetrix microarray analysis of LNCaP and LNCaP-AI (androgen-independent variant LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells. We showed that LEF1 overexpression in LNCaP cells resulted in increased AR expression and consequently enhanced growth and invasion ability, whereas LEF1 knockdown in LNCaP-AI cells decreased AR expression and, subsequently, growth and invasion capacity. Chromatin immunoprecipitation, gel shift, and luciferase assays confirmed LEF1 occupancy and regulation of the AR promoter. Thus, we identified LEF1 as a potential marker for androgen-independent disease and as a key regulator of AR expression and prostate cancer growth and invasion. LEF1 is highly expressed in androgen-independent prostate cancer, potentially serving as a marker for androgen-independent disease.
Properties and Biological Activities of Thioredoxins
Authors: Garth Powis, William R Montfort
Journal: The Annual Review of Pharmacology and Toxicology (2001)

The mammalian thioredoxins are a family of small (approximately 12 kDa) redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in turn reduce oxidized cysteine groups on proteins. The two main thioredoxins are thioredoxin-1, a cytosolic and nuclear form, and thioredoxin-2, a mitochondrial form. Thioredoxin-1 has been studied more. It performs many biological actions including the supply of reducing equivalents to thioredoxin peroxidases and ribonucleotide reductase, the regulation of transcription factor activity, and the regulation of enzyme activity by heterodimer formation. Thioredoxin-1 stimulates cell growth and is an inhibitor of apoptosis. Thioredoxins may play a role in a variety of human diseases including cancer. An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity.
Triple therapy in idiopathic pulmonary fibrosis: an alarming press release
Authors: A.U. Wells, J. Behr, U. Costabel, V. Cottin, V. Poletti
Journal: European Respiratory Journal (2012)

the National Heart, Lung, and Blood Institute (NHLBI), announced by press release that the prednisolone/azathioprine/N-acetylcysteine (triple therapy) arm of the PANTHER study (Prednisone, Azathioprine and N-acetylcysteine: a Study That Evaluates Response in IPF) had been discontinued [1].Compared with patients receiving placebo, patients with idiopathic pulmonary fibrosis (IPF) treated with triple therapy had excess deaths (11% versus 1%), more hospitalisations (29% versus 8%) and a higher prevalence of serious adverse events (31% versus 9%).The study is continuing with the N-acetylcysteine and placebo arms only.No concerns have been raised as a result of preliminary analysis of the N-acetylcysteine monotherapy arm of the PANTHER study.The preliminary announcement by the NHLBI has no immediate implications with regard to the introduction or continuation of N-acetylcysteine in IPF.
Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment
Authors: Yohei Morita, Hideo Ema, Hiromitsu Nakauchi
Journal: The Journal of Experimental Medicine (2010)

Hematopoietic stem cells (HSCs) have been extensively characterized based on functional definitions determined by experimental transplantation into lethally irradiated mice. In mice, HSCs are heterogeneous with regard to self-renewal potential, in vitro colony-forming activity, and in vivo behavior. We attempted prospective isolation of HSC subsets with distinct properties among CD34−/low c-Kit+Sca-1+Lin− (CD34−KSL) cells. CD34−KSL cells were divided, based on CD150 expression, into three fractions: CD150high, CD150med, and CD150neg cells. Compared with the other two fractions, CD150high cells were significantly enriched in HSCs, with great self-renewal potential. In vitro colony assays revealed that decreased expression of CD150 was associated with reduced erythroblast/megakaryocyte differentiation potential. All three fractions were regenerated only from CD150high cells in recipient mice. Using single-cell transplantation studies, we found that a fraction of CD150high cells displayed latent and barely detectable myeloid engraftment in primary-recipient mice but progressive and multilineage reconstitution in secondary-recipient mice. These findings highlight the complexity and hierarchy of reconstitution capability, even among HSCs in the most primitive compartment.
miR-155 Promotes T Follicular Helper Cell Accumulation during Chronic, Low-Grade Inflammation
Authors: Ruozhen Hu, Dominique A. Kagele, Thomas B. Huffaker, Marah C. Runtsch, Margaret Alexander, Jin Liu, Erin Bake, Wei Su, Matthew A. Williams, Dinesh S. Rao, Thomas Möller, Gwenn A. Garden, June L. Round, Ryan M. O’Connell
Journal: Immunity (2014)
Caveolin-1 opens endothelial cell junctions by targeting catenins
Authors: Romy Kronstein, Jochen Seebach, Sylvia Großklaus, Carsten Minten, Britta Engelhardt, Marek Drab, Stefan Liebner, Yvan Arsenijevic, Abdallah Abu Taha, Tatiana Afanasieva, Hans-Joachim Schnittler
Journal: Cardiovascular Research (2011)

A fundamental phenomenon in inflammation is the loss of endothelial barrier function, in which the opening of endothelial cell junctions plays a central role. However, the molecular mechanisms that ultimately open the cell junctions are largely unknown. Impedance spectroscopy, biochemistry, and morphology were used to investigate the role of caveolin-1 in the regulation of thrombin-induced opening of cell junctions in cultured human and mouse endothelial cells. Here, we demonstrate that the vascular endothelial (VE) cadherin/catenin complex targets caveolin-1 to endothelial cell junctions. Association of caveolin-1 with VE-cadherin/catenin complexes is essential for the barrier function decrease in response to the pro-inflammatory mediator thrombin, which causes a reorganization of the complex in a rope ladder-like pattern accompanied by a loss of junction-associated actin filaments. Mechanistically, we show that in response to thrombin stimulation the protease-activated receptor 1 (PAR-1) causes phosphorylation of caveolin-1, which increasingly associates with β- and γ-catenin. Consequently, the association of β- and γ-catenin with VE-cadherin is weakened, thus allowing junction reorganization and a decrease in barrier function. Thrombin-induced opening of cell junctions is lost in caveolin-1-knockout endothelial cells and after expression of a Y/F-caveolin-1 mutant but is completely reconstituted after expression of wild-type caveolin-1. Our results highlight the pivotal role of caveolin-1 in VE-cadherin-mediated cell adhesion via catenins and, in turn, in barrier function regulation.
Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progression
Authors: S. Montoto, A. López-Guillermo, A. Altés, G. Perea, A. Ferrer, M. Camós, L. Villela, F. Bosch, J. Esteve, F. Cervantes, J. Bladé, B. Nomdedeu, E. Campo, J. Sierra, E. Montserrat
Journal: Annals of Oncology (2004)
Intestinal paracellular permeability during malnutrition in guinea pigs: effect of high dietary zinc.
Authors: P Rodriguez, N Darmon, P Chappuis, C Candalh, M A Blaton, C Bouchaud, M Heyman
Journal: Gut (1996)

BACKGROUND: Zinc has been shown to have beneficial effects in vitro on epithelial barrier function, and in vivo to reduce intestinal permeability in malnourished children with diarrhoea. AIMS: To determine whether malnutrition alters intestinal paracellular permeability, and whether zinc prevents such alterations. METHODS: Guinea pigs were fed a normal protein diet (NP group), a low protein diet (LP group), or a low protein diet enriched with 1800 ppm zinc (LPZn group) for three weeks. Intestinal permeability was measured on jejunal segments mounted in Ussing chambers by measuring ionic conductance and mucosal to serosal fluxes of 14C-mannitol, 22Na, and horseradish peroxidase. Tight junction morphology was assessed on cryofracture replicas. RESULTS: Mannitol and Na fluxes and ionic conductance increased in the LP group compared with the NP group but remained normal in the LPZn group. Accordingly, jejunal epithelia from the LP group, but not from the LPZn group, showed a small decrease in number of tight junctional strands compared with epithelia from the NP group. Neither malnutrition nor zinc treatment modified horseradish peroxidase fluxes. CONCLUSIONS: Malnutrition is associated with increased intestinal paracellular permeability to small molecules, and pharmacological doses of zinc prevent such functional abnormality.
Which heart failure patients profit from natriuretic peptide guided therapy? A meta‐analysis from individual patient data of randomized trials
Authors: Hans‐Peter Brunner‐La Rocca, Luc Eurlings, A. Mark Richards, James L. Januzzi, Matthias E. Pfisterer, Ulf Dahlström, Yigal M. Pinto, Patric Karlström, Hans Erntell, Rudolf Berger, Hans Persson, Christopher M. O'Connor, Deddo Moertl, Hanna K. Gaggin, Christopher M. Frampton, M. Gary Nicholls, Richard W. Troughton
Journal: European Journal of Heart Failure (2015)
Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis
Authors: Pei Wang, Tian-Ying Xu, Yun-Feng Guan, Yan Zhao, Zhi-Yong Li, Xiao-Hong Lan, Xia Wang, Peng-Yuan Yang, Zhi-Min Kang, Paul M. Vanhoutte, Chao-Yu Miao
Journal: Cardiovascular Research (2014)

Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease.
Smoking in movies and adolescent smoking: cross-cultural study in six European countries
Authors: M. Morgenstern, E. A. P. Poelen, R. Scholte, S. Karlsdottir, S. H. Jonsson, F. Mathis, F. Faggiano, E. Florek, H. Sweeting, K. Hunt, J. D. Sargent, R. Hanewinkel
Journal: Thorax (2011)

<h3>Aim</h3> To investigate whether the association between exposure to smoking in movies and smoking among youth is independent of cultural context. <h3>Method</h3> Cross-sectional survey of 16 551 pupils recruited in Germany, Iceland, Italy, the Netherlands, Poland and Scotland with a mean age of 13.4 years (SD=1.18) and an equal gender distribution. School-based surveys were conducted between November 2009 and June 2010. Using previously validated methods, exposure to movie smoking was estimated from the 250 top-grossing movies of each country (years 2004–2009) and related to ever smoking. <h3>Results</h3> Overall, 29% of the sample had tried smoking. The sample quartile (Q) of movie smoking exposure was significantly associated with the prevalence of ever smoking: 14% of adolescents in Q1 had tried smoking, 21% in Q2, 29% in Q3 and 36% in Q4. After controlling for age, gender, family affluence, school performance, television screen time, number of movies seen, sensation seeking and rebelliousness and smoking within the social environment (peers, parents and siblings), the adjusted ORs for having tried smoking in the entire sample were 1.3 (95% CI 1.1 to 1.5) for adolescents in Q2, 1.6 (95% CI 1.4 to 1.9) for Q3 and 1.7 (95% CI 1.4 to 2.0) for Q4 compared with Q1. The adjusted relationship between ever smoking and higher movie smoking exposure levels was significant in all countries with a non-linear association in Italy and Poland. <h3>Conclusions</h3> The link between smoking in movies and adolescent smoking is robust and transcends different cultural contexts. Limiting young people9s exposure to movie smoking could have important public health implications.
Response to A.A.M. van der Veldt et al
Authors: Bernward Zeller, Christian K. Tamnes, Adriani Kanellopoulos, Inge K. Amlien, Stein Andersson, Paulina Due-Tønnessen, Anders M. Fjell, Kristine B. Walhovd, Lars T. Westlye, Ellen Ruud
Journal: Journal of Clinical Oncology (2013)