tbuckley/cabot-search huggingface dataset:
Genome-wide profiling using single-nucleotide polymorphism arrays identifies novel chromosomal imbalances in pediatric glioblastomas
Authors: Hui-Qi Qu, Karine Jacob, Sarah Fatet, Bing Ge, David Barnett, Olivier Delattre, Damien Faury, Alexandre Montpetit, Lauren Solomon, Peter Hauser, Miklos Garami, Laszlo Bognar, Zoltan Hansely, Robert Mio, Jean-Pierre Farmer, Steffen Albrecht, Constantin Polychronakos, Cynthia Hawkins, Nada Jabado
Journal: Neuro-Oncology (2010)

Available data on genetic events in pediatric grade IV astrocytomas (glioblastoma [pGBM]) are scarce. This has traditionally been a major impediment in understanding the pathogenesis of this tumor and in developing ways for more effective management. Our aim is to chart DNA copy number aberrations (CNAs) and get insight into genetic pathways involved in pGBM. Using the Illumina Infinium Human-1 bead-chip-array (100K single-nucleotide polymorphisms [SNPs]), we genotyped 18 pediatric and 6 adult GBMs. Results were compared to BAC-array profiles harvested on 16 of the same pGBM, to an independent data set of 9 pediatric high-grade astrocytomas (HGAs) analyzed on Affymetrix 250K-SNP arrays, and to existing data sets on HGAs. CNAs were additionally validated by real-time qPCR in a set of genes in pGBM. Our results identify with nonrandom clustering of CNAs in several novel, previously not reported, genomic regions, suggesting that alterations in tumor suppressors and genes involved in the regulation of RNA processing and the cell cycle are major events in the pathogenesis of pGBM. Most regions were distinct from CNAs in aGBMs and show an unexpectedly low frequency of genetic amplification and homozygous deletions and a high frequency of loss of heterozygosity for a high-grade I rapidly dividing tumor. This first, complete, high-resolution profiling of the tumor cell genome fills an important gap in studies on pGBM. It ultimately guides the mapping of oncogenic networks unique to pGBM, identification of the related therapeutic predictors and targets, and development of more effective therapies. It further shows that, despite commonalities in a few CNAs, pGBM and aGBMs are two different diseases.
Toward a Global Phylogeny of the Brassicaceae
Authors: C. Donovan Bailey, Marcus A. Koch, Michael Mayer, Klaus Mummenhoff, Steve L. O'Kane, Suzanne I. Warwick, Michael D. Windham, Ihsan A. Al-Shehbaz
Journal: Molecular Biology and Evolution (2006)

The Brassicaceae is a large plant family (338 genera and 3,700 species) of major scientific and economic importance. The taxonomy of this group has been plagued by convergent evolution in nearly every morphological feature used to define tribes and genera. Phylogenetic analysis of 746 nrDNA internal transcribed spacer (ITS) sequences, representing 24 of the 25 currently recognized tribes, 146 genera, and 461 species of Brassicaceae, produced the most comprehensive, single-locus–based phylogenetic analysis of the family published to date. Novel approaches to nrDNA ITS analysis and extensive taxonomic sampling offered a test of monophyly for a large complement of the currently recognized tribes and genera of Brassicaceae. In the most comprehensive analysis, tribes Alysseae, Anchonieae plus Hesperideae, Boechereae, Cardamineae, Eutremeae, Halimolobeae, Iberideae, Noccaeeae, Physarieae, Schizopetaleae, Smelowskieae, and Thlaspideae were all monophyletic. Several broadly defined genera (e.g., Draba and Smelowskia) were supported as monophyletic, whereas others (e.g., Sisymbrium and Alyssum) were clearly polyphyletic. Analyses of ITS data identified several problematic sequences attributable to errors in sample identification or database submission. Results from parsimony ratchet and Bayesian analyses recovered little support for the backbone of the phylogeny, suggesting that many lineages of Brassicaceae have undergone rapid radiations that may ultimately be difficult to resolve with any single locus. However, the development of a preliminary supermatrix including the combination of 10 loci for 65 species provides an initial estimate of intertribal relations and suggests that broad application of such a method will provide greater understanding of relationships in the family.
RELATIONSHIP OF A NEW GROWTH FACTOR REQUIRED BY CERTAIN HEMOLYTIC STREPTOCOCCI TO GROWTH PHENOMENA IN OTHER BACTERIA
Authors: Herbert Sprince, D. W. Woolley
Journal: The Journal of Experimental Medicine (1944)

By a series of quantitative assays of concentrates prepared in a variety of ways, it has been shown that the previously described growth factor now called "strepogenin," required by certain hemolytic streptococci, is very similar to and possibly identical with the recently described growth factors for Lactobacillus casei and Smith's Streptococcus lactis. An improved procedure for assay of strepogenin with the aid of Lactobacillus casei has been described, and additional properties of the growth factor have been presented.
High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial
Authors: B. Bui-Nguyen, I. Ray-Coquard, C. Chevreau, N. Penel, J.O. Bay, J.M. Coindre, D. Cupissol, A. Italiano, F. Bonichon, J.P. Lotz, A. Thyss, M. Jimenez, S. Mathoulin-Pélissier, J.Y. Blay
Journal: Annals of Oncology (2011)
Vascular smooth muscle cell hypertrophy and hyperploidy in the Goldblatt hypertensive rat.
Authors: G K Owens, S M Schwartz
Journal: Circulation Research (1983)

Our major objective in this study was to examine the hypothesis that the aortic smooth muscle cell hypertrophy and hyperploidy observed in previous studies of spontaneously hypertensive rats is not peculiar to that model, but also occurs in Sprague-Dawley rats made hypertensive by a Goldblatt procedure (two-kidney, one-clip model). Flow microfluorometric and microdensitometric analysis of smooth muscle cell DNA content showed a significant increase in the frequency of tetraploid smooth muscle cells from 5.6 +/- 0.9% in controls to 14.6 +/- 1.94% in hypertensives 1 month after Goldblatt surgery. Neither differences in ploidy nor elevation in blood pressure were apparent 2 weeks after surgery. The frequency of polyploid smooth muscle cells increased with age, duration of hypertension, and level of blood pressure. Analysis of the interrelationship between smooth muscle cell ploidy and hypertrophy in 5-month post-surgery Goldblatts by cytospectrophotometric measurements of the protein and DNA content of individual smooth muscle cells showed that tetraploid and octaploid cells from Goldblatt rats had 64% and 129% greater protein mass, respectively, than diploid cells. In addition, the mean protein mass of smooth muscle cells from Goldblatts was approximately 100% greater than that of normotensive controls, with each of the ploidy classes in Goldblatts having a higher frequency and mass than the corresponding cells in controls. Estimates of cell number per centimeter aortic length, based on measurements of average DNA/cell and total aortic medial DNA, showed no difference between hypertensives and controls. Furthermore, the rate of accumulation of polyploid cells could account for the increased frequency of cells undergoing DNA synthesis as measured by [3H]thymidine autoradiography. Thus, smooth muscle cell hypertrophy, not hyperplasia, was responsible for the increased mass of smooth muscle in aortas of Goldblatt hypertensive rats compared with normotensive controls, and this smooth muscle cell hypertrophy was accompanied by an increase in DNA ploidy.
Improvement of tidal breathing pattern analysis in children with asthma by on-line automatic data processing
Authors: CK van der Ent, HJ Brackel, P Mulder, JM Bogaard
Journal: European Respiratory Journal (1996)

The time taken to achieve peak tidal expiratory flow as a proportion of total expiratory time (t PTEF/t E) during tidal breathing (TB) is used as a parameter of airway obstruction in children with asthma. Curve selection bias is one of the most important limitations to the method. This study evaluates three curve selection methods, including a computer program, which on-line selects and analyses TB curves (Masterscreen Paediatric; Jaeger, Germany). TB analysis was performed in 26 children (aged 4-7 yrs) with asthma, before and after methacholine provocation and after subsequent bronchodilatation. Levels and stability of TB parameters derived from computer-selected, unselected and unbiased eye-selected curves were compared. t PTEF/t E ratios of the computer-selected curves agreed well with the unbiased eye-selected curves (limits of agreement -4.8 and +5.8%), but were significantly different from the ratios of unselected curves. Computer-derived t PTEF/t E ratios had the highest level of stability: the reliability coefficient of baseline measurements was 0.96 for computer selection, 0.84 for eye selection and 0.87 for no selection (reliability index = 1 at maximal stability). Tidal volume, respiratory rate, inspiratory and expiratory time were also assessed accurately by the computer program. The mean t PTEF/t E ratio (computer selection) dropped after methacholine provocation (from 30 +/- 9 to 22 +/- 9% at provocative dose at which forced expiratory volume in one second had dropped &gt; or = 20% from baseline (FEV1-PD20 level), p &lt; 0.001) and was restored after bronchodilation (30 +/- 6%; p &lt; 0.001). We conclude that on-line computer analysis is preferable to no selection and to by-eye selection. The use of the program avoids curve selection bias and enhances the applicability of tidal breathing analysis as a measure of airflow obstruction in young children.
96 NOTCH1 DELETION IN HEPATOCYTES PREDISPOSES TO DIABETES AND LIVER STEATOSIS THROUGH DYSREGULATION OF GENES INVOLVED IN GLUCOSE AND LIPID HOMEOSTASIS
Authors: C. Bernsmeier, M.T. Dill, A. Provenzano, Z. Makowska, K. Huser, D. Semela, L. Tornillo, F. Marra, M.H. Heim
Journal: Journal of Hepatology (2012)
Sex differences in emphysema phenotype in smokers without airflow obstruction
Authors: N. Sverzellati, E. Calabro, G. Randi, C. La Vecchia, A. Marchiano, J-M. Kuhnigk, M. Zompatori, P. Spagnolo, U. Pastorino
Journal: European Respiratory Journal (2009)

Data on sex differences in emphysema are limited to chronic obstructive pulmonary disease. We aimed to verify whether such differences also exist in smokers without airflow obstruction, weighting their influence on the relationship between emphysema and clinical features. We evaluated both clinical and multidetector computed tomography (MDCT) data of 1,011 heavy smokers recruited by a lung cancer screening project. MDCT scans were analysed with software allowing lobar quantification of emphysema features. For these measures, multiple regression models were applied to assess the effect of patients sex, after allowance for age, body mass index (BMI), smoking history, forced expiratory volume in 1 s (FEV<sub>1</sub>) and forced vital capacity. The final study cohort consisted of 957 smokers without airflow obstruction. Compared with males, females exhibited an emphysema phenotype less extensive in each pulmonary lobe, characterised by smaller emphysematous areas and less concentrated in the core of the lung. However, in females, the increase of emphysema with age was more pronounced and displayed a more significant relationship with FEV<sub>1</sub>% decline; conversely, in males there was a stronger association with the decrease in BMI. Males and females respond differently to the type and location of lung damage due to tobacco exposure. In smokers, sex influences the relationship between emphysema and clinical features.
Navigating the Therapeutic Complexity of PI3K Pathway Inhibition in Melanoma
Authors: Lawrence N. Kwong, Michael A. Davies
Journal: Clinical Cancer Research (2013)

Abstract Melanoma is entering into an era of combinatorial approaches to build upon recent clinical breakthroughs achieved by novel single-agent therapies. One of the leading targets to emerge from the growing understanding of the molecular pathogenesis, heterogeneity, and resistance mechanisms of melanomas is the phosphoinositide 3-kinase (PI3K)–AKT pathway. Multiple genetic and epigenetic aberrations that activate this pathway have been identified in melanomas de novo and in acquired resistance models. These developments have been paralleled by the establishment of models for preclinical testing and the availability of compounds that target various effectors in the pathway. Thus, in addition to having a strong rationale for targeting, the PI3K–AKT pathway presents an immediate clinical opportunity. However, the development of effective strategies against this pathway must overcome several key challenges, including optimizing patient selection, overcoming feedback loops, and pathway cross-talk that can mediate resistance. This review discusses the current understanding and ongoing research about the PI3K–AKT pathway in melanoma and emerging strategies to achieve clinical benefit in patients by targeting it. Clin Cancer Res; 19(19); 5310–9. ©2013 AACR.
Effect of first-phase polarity of biphasic shocks on defibrillation threshold with a single transvenous lead system
Authors: S. Adam Strickberger, K. Ching Man, Emile Daoud, Maureen P. Neary, Laura E. Horwood, Mark Niebauer, John D. Hummel, Fred Morady
Journal: Journal of the American College of Cardiology (1995)
Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein.
Authors: L M Colletti, S L Kunkel, A Walz, M D Burdick, R G Kunkel, C A Wilke, R M Strieter
Journal: Journal of Clinical Investigation (1995)

The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. One of the striking consequences of liver injury is the associated pulmonary dysfunction that may be related to the release of hepatic-derived cytokines. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and demonstrated that this injury causes the production and release of hepatic-derived TNF, which mediates a neutrophil-dependent pulmonary microvascular injury. In this study, we have extended these previous observations to assess whether an interrelationship between TNF and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein-78 (ENA-78), exists that may be accountable for the pathology of lung injury found in this model. In the context of hepatic ischemia/reperfusion injury, we demonstrated the following alterations in lung pathophysiology: (a) an increase in pulmonary microvascular permeability, lung neutrophil sequestration, and production of pulmonary-derived ENA-78; (b) passive immunization with neutralizing TNF antiserum resulted in a significant suppression of pulmonary-derived ENA-78; and (c) passive immunization with neutralizing ENA-78 antiserum resulted in a significant attenuation of pulmonary neutrophil sequestration and microvascular permeability similar to our previous studies with anti-TNF. These findings support the notion that pulmonary ENA-78 produced in response to hepatic-derived TNF is an important mediator of lung injury.
Breast Cancer Risk: Effects of Estrogen Replacement Therapy and Body Mass
Authors: R. E. Harris, K. K. Namboodiri, E. L. Wynder
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Epidemiologic studies have focused on the association between breast cancer risk and a variety of lifestyle and exogenous factors. Purpose : The purpose of this study was to clarify the effects of alcohol consumption, cigarette smoking, oral contraceptive (OC) use, estrogen replacement therapy (ERT), and body mass on risk of breast cancer. Methods : These variables were examined in a case-control study of 604 patients with newly diagnosed breast cancer and 520 control subjects who did not have breast cancer and were frequency matched for age, hospital, and time of diagnosis. These case patients and control subjects were part of an ongoing study of breast cancer by the American Health Foundation and were selected for interview from hospitals in the New York City area from January 1987 through December 1989. The data were analyzed by computation of odds ratios (ORs) for potential risk factors, with adjustment for age at diagnosis and other potential confounding variables and with stratification by menopausal status. Results : We observed positive effects of ERT and high body mass on the risk of postmenopausal breast cancer, particularly when each factor was examined in the absence of the other factor. In lean postmentopausal woamen, the adjusted summary OR associated with ERT was significantly elevated (OR = 2.0; 95% confidence interval [CI] = 1.1–3.5; P<01), and there was a statistically significant dose response of breast cancer risk with ERT duration ( adjusted ORs = 2.0 for <5 years and 2.2 for≥5years; positive trend, P&lt.02). Reciprocally, in women who did not receive ERT, high body mass (Quetelet index > 27) was a significant risk factor for postmenopausal breast cancer (OR = 2.1; 95& CI = 1.3–3.3; P<.02), and the liner trend in risk with increasing body mass was significant (positive trend, P<.02). The strongest effect of body mass occurred in women who were lean at age 18 and gained enough weight to place them in the upper tertile of body mass at the time of diagnosis (OR = 2.6; 95& CI = 1.5–4.6; P<.01). There was no evidence of significant positive associations between breast cancer risk and cigarette smoking, alcohol consumption, or OC use in any subgroup of these women. Conclusions : our results support the hypothesis that excess adipose deposition heightens breast cancer risk in the postmeno pausal years. Furthermore, they underscore the need for continuing investigation of the effects of exogenous estrogens on the development of this malignancy, Particularly in lean postmenopausal women. [J Natl Cancer Inst 84:1575–1582, 1992]
Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-β1 secretion and the resolution of inflammation
Authors: Mai-Lan N. Huynh, Valerie A. Fadok, Peter M. Henson
Journal: Journal of Clinical Investigation (2002)

Ingestion of apoptotic cells in vitro by macrophages induces TGF-β1 secretion, resulting in an anti-inflammatory effect and suppression of proinflammatory mediators. Here, we show in vivo that direct instillation of apoptotic cells enhanced the resolution of acute inflammation. This enhancement appeared to require phosphatidylserine (PS) on the apoptotic cells and local induction of TGF-β1. Working with thioglycollate-stimulated peritonea or LPS-stimulated lungs, we examined the effect of apoptotic cell uptake on TGF-β1 induction. Viable or opsonized apoptotic human Jurkat T cells, or apoptotic PLB-985 cells, human monomyelocytes that do not express PS during apoptosis, failed to induce TGF-β1. PS liposomes, or PS directly transferred onto the PLB-985 surface membranes, restored the TGF-β1 induction. Apoptotic cell instillation into LPS-stimulated lungs reduced proinflammatory chemokine levels in the bronchoalveolar lavage fluid (BALF). Additionally, total inflammatory cell counts in the BALF were markedly reduced 1–5 days after apoptotic cell instillation, an effect that could be reversed by opsonization or coinstillation of TGF-β1 neutralizing antibody. This reduction resulted from early decrease in neutrophils and later decreases in lymphocytes and macrophages. In conclusion, apoptotic cell recognition and clearance, via exposure of PS and ligation of its receptor, induce TGF-β1 secretion, resulting in accelerated resolution of inflammation.
Routine versus As-Needed Bevacizumab with 12-Weekly Assessment Intervals for Neovascular Age-Related Macular Degeneration
Authors: Sajjad Mahmood, Stephen A. Roberts, Tariq M. Aslam, Jeremy Parkes, Kate Barugh, Paul N. Bishop
Journal: Ophthalmology (2015)

<h3>Purpose</h3> To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD) using 2 different treatment regimens in which patients were assessed clinically at up to 12-week intervals. <h3>Design</h3> Randomized, controlled, noninferiority trial. <h3>Participants</h3> A total of 331 patients with nAMD. <h3>Methods</h3> Patients were treated with 1.25 mg intravitreal bevacizumab and followed up to 92 weeks. They were randomized into 2 arms. All patients received 3 loading doses 4 weeks apart and thereafter were assessed every 12 weeks until the end of the study. One arm received a routine treatment at each 12-week assessment, and the other arm was treated at these assessments on an as-needed basis. After the loading doses, patients in either arm who showed signs of disease activity had an additional assessment after 6 weeks and at that visit had top-up treatments on an as-needed basis. <h3>Main Outcome Measures</h3> Mean best-corrected visual acuity (BCVA) at 92 weeks. <h3>Results</h3> At 92 weeks, patients who had treatments every 12 weeks had superior BCVA to those treated on an as-needed basis every 12 weeks (<i>P</i> = 0.008), with the regular treatment arm gaining a mean BCVA of 5.5 letters and the as-needed treatment arm gaining 0.6 letters. The regular treatment arm of the study showed significantly improved outcomes with respect to 5-, 10-, and 15-letter changes in BCVA from baseline compared with the as-needed treatment arm, as well as superior reading speed. In patients who completed the study, up to but not including week 92, the mean number of treatments was 10.8 for the regular treatment arm and 9.1 for the as-needed treatment arm. <h3>Conclusions</h3> A treatment regimen with regular bevacizumab injections every 12 weeks after loading doses supplemented with as-needed top-up treatments produced a stable improvement in BCVA from baseline. The improvement in BCVA was broadly similar to that obtained in other studies using anti-vascular endothelial growth factor drugs with more frequent assessments and treatments.
A case of jaundice in portal hypertension
Authors: Shivali Vaibhav Kashikar, Tony C K Tham, Money Bansal, Bhushan Lakhkar, Gaurav Prakash Manikpure
Journal: Gut (2013)

A 38-year-old woman, diagnosed with portal hypertension 8 months back, presented with painless jaundice. Her synthetic liver function was normal and serology was negative for hepatitis virus. Liver function tests showed total serum bilirubin 321 mmol/l, serum alanine aminotransferase 59 IU/l, aspartate aminotransferase 80 IU/l, γ-glutamyltransferase 114 IU/l and serum alkaline phosphatase 296 IU/l. CT of the abdomen showed hepatosplenomegaly, ascites and intrahepatic and extrahepatic biliary ductal dilatation (figure 1). The common bile duct showed smooth tapering distally without any mass. The main portal vein was replaced by a large cavernoma and multiple collaterals were seen at systemic-portal sites. This portal cavernoma …