tbuckley/cabot-search huggingface dataset:
Abstract P3-04-04: Amplification and overexpression of TLK2 promote genomic instability in invasive breast cancer
Authors: J-A Kim, X CAO, Y Tan, X Wang, R Schiff, X Wang
Journal: Cancer Research (2013)

Abstract The accumulation of numerous chromosomal aberrations is a hallmark characteristic of invasive breast cancer (IBC). It is thus critical to find specific chromosomal aberrations that may drive breast cancer initiation and progression, particularly those that are drivers of the genomic instability. By integrative analysis of genomic data from The Cancer Genome Atlas (TCGA), we have nominated Tousled-Like Kinase 2 (TLK2) as a candidate oncogene target for IBC. Ultra-high resolution copy-number data from TCGA suggest that TLK2 was amplified in approximately 10% of IBC, which are more frequent in luminal B than luminal A tumors. These data also revealed that TLK2-high breast tumors harbor significantly more global copy-number aberrations than the TLK2 low-tumors. TLK2 is a nuclear serine/threonine kinase that serves as a cell cycle checkpoint regulating chromatin assembly, and in response to DNA damage, TLK2 can be inactivated by phosphorylation through the ATM-dependent pathway. We thus postulated that up-regulation of TLK2 may help cancer cells to surpass the cell cycle checkpoint upon DNA damage, which may promote genomic instability in breast cancer cells. To analyze the effect of TLK2 overexpression, we introduced an inducible expression vector containing the TLK2 open-reading frame into the MCF10A benign epithelial cells and the T47D breast cancer cells. As shown by fluorescence activated cell sorting (FACS), ectopic expression of TLK2 in these cells overcame the cell cycle checkpoint in response to the DNA damage induced by gamma irradiation. gamma-H2AX foci formation revealed increased DNA double strand breaks and prolonged DNA repair window after irradiation in the TLK2 overexpressing cells. Interestingly, immunofluorescence localized TLK2 to the nucleus of breast cancer cells, which was markedly enriched in DNA double-strand break foci (or gamma-H2AX foci). To examine the effect of TLK2 knockdown, the MCF7 and MDAMB361 breast cancer cells overexpressing TLK2 were transfected with different TLK2 siRNAs. TLK2 inhibition led to G1/S cell cycle arrest (FACS analysis), profound decrease in cell growth (MTT assay), and enhanced apoptosis (Annexin V assay) in the MCF7 and MDAMB361 breast cancer cells over-expressing TLK2. Together, this study supports the role of TLK2 deregulation in the increased genomic instability of TLK2-high breast cancers, and suggests its potential as an attractive therapeutic target. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-04-04.
Endoscopic Ultrasound Drainage of Pancreatic Pseudocyst: A Prospective Comparison with Conventional Endoscopic Drainage
Authors: M. Kahaleh, V. Shami, M. Conaway, J. Tokar, T. Rockoff, S. De La Rue, E. de Lange, M. Bassignani, S. Gay, R. Adams, P. Yeaton
Journal: Endoscopy (2006)

Background and Study Aims: Pancreatic pseudocysts are a complication in up to 20 % of patients with pancreatitis. Endoscopic management of pseudocysts by a conventional transenteric technique, i. e. conventional transmural drainage (CTD), or by endoscopic ultrasound-guided drainage (EUD), is well described. Our aim was to prospectively compare the short-term and long-term results of CTD and EUD in the management of pseudocysts. Patients and Methods: A total of 99 consecutive patients underwent endoscopic management of pancreatic pseudocysts according to this predetermined treatment algorithm: patients with bulging lesions without obvious portal hypertension underwent CTD; all remaining patients underwent EUD. Patients were followed prospectively, with cross-sectional imaging during clinic visits. We compared short-term and long-term results (effectiveness and complications) at 1 and 6 months post procedure.
Increased Risk of Primary Sclerosing Cholangitis and Ulcerative Colitis in First-Degree Relatives of Patients With Primary Sclerosing Cholangitis
Authors: Annika Bergquist, Scott M Montgomery, Shahram Bahmanyar, Rolf Olsson, Ake Danielsson, Stefan Lindgren, Hanne Prytz, Rolf Hultcrantz, L A R S Lööf, Hanna Sandberg-Gertzén, Sven Almer, Johan Askling, Anna Ehlin, Anders Ekbom
Journal: Clinical Gastroenterology and Hepatology (2008)
p53 — Master and Commander
Authors: William D. Foulkes
Journal: New England Journal of Medicine (2007)

The gene known variously as p53, TP53, and Trp53 is currently featured in nearly 45,000 published articles listed in PubMed — a remarkable number suggesting that the protein product of this gene, p53, is one of the most important molecules in biology. When it was discovered in 1979, the p53 phosphoprotein (molecular mass, 53 kD) was postulated to have "a crucial role in the modulation of the transformed state."1 This idea has found support in innumerable studies, including the one reported on by Poeta et al. in this issue of the Journal (pages 2552–2561), in which somatic mutations in TP53 . . .
Circus movement in the canine atrium around the tricuspid ring during experimental atrial flutter and during reentry in vitro.
Authors: L H Frame, R L Page, P A Boyden, J J Fenoglio, B F Hoffman
Journal: Circulation (1987)

A Y-shaped lesion in the right atrium allows induction of atrial flutter in dogs. We recorded the activation sequence during this tachycardia from 96 endocardial bipolar electrodes using intracavitary electrode arrays during 12 separate episodes in three isolated perfused hearts. In each case a reentrant impulse circulated around the tricuspid valve orifice in either a clockwise or counter-clockwise direction. Cutting the pathway terminated the rhythm and prevented its reinduction. There was no discrete segment of markedly slow conduction in the reentrant circuit. The tachycardia cycle length was decreased by methacholine and increased by lidocaine. Reentry was also induced in atrial tissue around the tricuspid orifice when this structure was isolated and superfused in vitro. Tachycardia cycle lengths varied from 205 to 399 msec, depending on the circumference of the ring and temperature. Induction of tachycardia by premature stimulation depended on differences in the duration of the effective refractory period among parts of the ring. Conduction velocity was relatively uniform and was slower during tachycardias than during pacing at long cycle lengths. Analysis of the response to premature stimuli that reset the tachycardia provided evidence for incomplete recovery of excitability between depolarizations during the tachycardia. Fast-response action potentials were recorded throughout the pathway and up to six to eight cell layers deep. Histologic studies showed the supravalvular lamina, a circumferential band of fibers several cell layers below the endocardial surface, to be continuous around the tricuspid orifice. Propagation through this layer best explains the conduction velocities observed in the intact heart during flutter in this preparation.
Genetic pathway to recurrent chromosome translocations in murine lymphoma involves V(D)J recombinase
Authors: Gary J. Vanasse, James Halbrook, Sushma Thomas, Abigail Burgess, Merl F. Hoekstra, Christine M. Disteche, Dennis M. Willerford
Journal: Journal of Clinical Investigation (1999)

Chromosome translocations involving antigen receptor loci are a genetic hallmark of non-Hodgkin's lymphomas in humans. Most commonly, these translocations result in juxtaposition of the immunoglobulin heavy-chain (IgH) locus with one of several cellular proto-oncogenes, leading to deregulated oncogene expression. The V(D)J recombinase, which mediates physiologic rearrangements of antigen receptor genes, may play a mechanistic role in some lymphoma translocations, although evidence is indirect. A high incidence of B-lineage lymphomas has been observed in mice with severe combined immunodeficiency (SCID) and p53-null mutations. We show that these tumors are characteristic of the pro–B-cell stage of development and that they harbor recurrent translocations involving chromosomes 12 and 15. Fluorescence in situ hybridization (FISH) shows retention of IgH sequences on the derivative chromosome 12, implying that breakpoints involve the IgH locus. Pro–B-cell lymphomas were suppressed in SCID p53–/– mice by a Rag-2–null mutation, demonstrating that DNA breaks generated during V(D)J recombination are required for oncogenic transformation, and suggesting that t(12;15) arise during attempted IgH rearrangement in pro-B cells. These studies indicate that the oncogenic potential inherent in antigen receptor diversification is controlled in vivo by efficient rejoining of DNA ends generated during V(D)J recombination and an intact cellular response to DNA damage.
Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: Report of 21 cases and review of the literature
Authors: V. Audard, F. Larousserie, P. Grimbert, M. Abtahi, J-J Sotto, A. Delmer, F. Boue, D. Nochy, N. Brousse, R. Delarue, P. Remy, P. Ronco, D. Sahali, P. Lang, O. Hermine
Journal: Kidney International (2006)
Limited pulmonary resection for peripheral small-sized adenocarcinoma of the lung
Authors: Yoshinobu Ichiki, Takeshi Hanagiri, Tetsuro Baba, Tetsuya So, Kenji Ono, Hidetaka Uramoto, Tomoko So, Mitsuhiro Takenoyama, Kosei Yasumoto
Journal: International Journal of Surgery (2010)
Benign outcome of hypertensive renal crisis in scleroderma.
Authors: M H Arnold, R Robinson
Journal: Annals of the Rheumatic Diseases (1989)

Benign outcome of hypertensive renal crisis in scleroderma SIR, Renal involvement may occur in up to 50% of patients with scleroderma, with considerable morbidity and mortality.'Before current, aggressive antihypertensive treatment a high proportion of patients who developed renal crisis died within several months of its onset.2'The
Testicular and Leptomeningeal Relapse as Myeloid Sarcoma in a Patient Initially Diagnosed with T Lymphoblastic Lymphoma
Authors: R. Ueda, D. Maruyama, A.M. Maeshima, K. Miyamoto, S. Fukuhara, S.-W. Kim, T. Watanabe, Y. Kobayashi, H. Taniguchi, K. Tobinai
Journal: Annals of Oncology (2013)
Assessment of Response of Esophageal Carcinoma to Induction Chemotherapy
Authors: M. L. Hordijk, T. C. Kok, J. H. P. Wilson, A. H. Mulder
Journal: Endoscopy (1993)

Endoscopic ultrasonography (EUS) is currently considered the best available technique for the local staging of esophageal cancer. In a prospective study 11 patients with esophageal squamous cell carcinoma were investigated to evaluate the usefulness of EUS in the assessment of response to induction chemotherapy. Response to chemotherapy was evaluated by means of history of dysphagia, endoscopy, computed tomography (CT) and EUS to assess relief of clinical symptoms, reduction of tumor bulk and depth of tumor invasion (T-stage). One patient was excluded because EUS failed. Tumor response was best correlated with relief of dysphagia and by tumor bulk reduction as determined on endoscopy and CT. We found it not useful to measure reduction of tumor bulk with EUS because of tumor compression by the instrument, stenosis, or the hypoechoic thickening of the esophageal wall caused by an inflammatory reaction after chemotherapy. There was no change in EUS T-staging after induction chemotherapy compared to prechemotherapy assessment. EUS T-staging after induction chemotherapy was accurate in 6 of 10 patients compared to the histopathologic examination of the resected specimen. There was EUS T3-overstaging in 4 patients, caused by partial or complete replacement of the tumor by an inflammatory reaction due to chemotherapy. We conclude that inflammatory changes induced by chemotherapy lead to EUS overstaging of the T stage thus making it a less reliable tool in restaging after chemotherapy.
Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans
Authors: Matthew W. Hulver, Jason R. Berggren, Michael J. Carper, Makoto Miyazaki, James M. Ntambi, Eric P. Hoffman, John P. Thyfault, Robert Stevens, G. Lynis Dohm, Joseph A. Houmard, Deborah M. Muoio
Journal: Cell Metabolism (2005)
Intrinsic Myocyte Dysfunction and Tyrosine Kinase Pathway Activation Underlie the Impaired Wall Thickening of Adjacent Regions During Postinfarct Left Ventricular Remodeling
Authors: Guido Melillo, João A.C. Lima, Robert M. Judd, Pascal J. Goldschmidt-Clermont, Howard S. Silverman
Journal: Circulation (1996)

Background Left ventricular remodeling after infarction is accompanied by dysfunction of regions adjacent to the infarct. We hypothesized that myocyte contractile abnormalities and elongation greater than in remote regions underlie adjacent-region dysfunction in the remodeled ventricle. The activation of the tyrosine kinase pathway, which mediates in vitro hypertrophy by stretch and/or angiotensin, was also assessed in myocytes separately isolated from adjacent and remote regions. Methods and Results ECG-gated magnetic resonance imaging short-axis images were acquired 2 weeks after coronary ligation in rats. After the rats were killed, myocytes were isolated from animals with large (n=7) and small (n=7) infarcts and from 4 sham-operated controls. Regional wall thickening was correlated with local myocyte function and morphology. Cytochemistry for tyrosine-phosphorylated proteins was performed in myocytes from the same regions. Remodeled ventricles were dilated relative to controls by 93.7%, and wall thickening in adjacent regions was less than in remote regions (27.8±6.11% versus 54.0±10.1%, P &lt;.01). In large infarcts, cell extent and velocity of shortening were reduced in adjacent cells versus controls by 47% and 44%, respectively ( P &lt;.05). Myocyte shortening was reduced in adjacent versus remote regions ( P &lt;.06), and cell dysfunction correlated with impaired wall thickening ( r =.72, P &lt;.05). Myocytes in adjacent regions were longer than in remote regions (150.3±1.89 versus 143.1±1.76 μm, P &lt;.05) and also showed 88% more membrane-related phosphotyrosine clusters ( P &lt;.05). Conclusions After infarction, impaired wall thickening in adjacent regions is accompanied by greater myocyte dysfunction and elongation than in remote regions. These abnormalities are associated with regional differences in the tyrosine kinase pathway activation, indicating a potential intracellular mechanism for postinfarct myocardial remodeling.
Homicide Rates and Firearm Availability-Reply
Authors: Lois A. Fingerhut
Journal: JAMA (1990)

In Reply.—  In our article, we state that the  proportion of firearm-related homicides in the United States suggests that the availability of handguns is a factor that deserves special attention. In the search for explanations of, and interventions to reduce, the high US homicide rate, we would be remiss if we did not consider the effect of firearm availability on the homicide rate. Three fourths of the homicides among males 15 to 24 years of age resulted from the use of firearms, compared with only 23% in the 14 other countries for which data were available. Furthermore, handguns accounted for three fourths of the firearm-related homicides in the United States, and although military weapons are widely available in Switzerland and Israel, each of these countries has strict laws regulating the licensing of handguns.  The role of factors other than handgun availability is important to consider. As of 1989, however,
Clinical Crossroads
Authors: Margaret A. Winker
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Prevention of Chronic Obstructive Pulmonary Disease Exacerbations by Salmeterol/Fluticasone Propionate or Tiotropium Bromide
Authors: Jadwiga A. Wedzicha, Peter M. A. Calverley, Terence A. Seemungal, Gerry Hagan, Zainab Ansari, Robert A. Stockley
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease (COPD).We compared the relative efficacy of the long-acting inhaled bronchodilator/antiinflammatory combination (salmeterol/fluticasone propionate) 50/500 microg twice daily and the long-acting bronchodilator (tiotropium) 18 microg once daily in preventing exacerbations and related outcomes in severe and very severe COPD.A total of 1,323 patients (mean age, 64 yr, post-bronchodilator FEV1, 39% predicted) were randomized in this 2-year, double-blind, double-dummy parallel study.Primary endpoint was health care utilization exacerbation rate. Other endpoints included health status measured by St. George's Respiratory Questionnaire (SGRQ), mortality, adverse events, and study withdrawal. Probability of withdrawing from the study was 29% greater with tiotropium than salmeterol/fluticasone propionate (P = 0.005). The modeled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio, 0.967; 95% confidence interval [CI], 0.836-1.119]; P = 0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionate versus tiotropium (difference 2.1 units; 95% CI, 0.1-4.0; P = 0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3%) of patients in this group died compared with 38 (6%) in the tiotropium group (P = 0.032). More pneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (P = 0.008).We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study while receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate-treated patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00361959).
Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis
Authors: Chris J. Weston, Emma L. Shepherd, Lee C. Claridge, Pia Rantakari, Stuart M. Curbishley, Jeremy W. Tomlinson, Stefan G. Hubscher, Gary M. Reynolds, Kristiina Aalto, Quentin M. Anstee, Sirpa Jalkanen, Marko Salmi, David J. Smith, Christopher P. Day, David H. Adams
Journal: Journal of Clinical Investigation (2014)

Nonalcoholic fatty liver disease (NAFLD) encompasses a range of manifestations, including steatosis and cirrhosis. Progressive disease is characterized by hepatic leukocyte accumulation in the form of steatohepatitis. The adhesion molecule vascular adhesion protein-1 (VAP-1) is a membrane-bound amine oxidase that promotes leukocyte recruitment to the liver, and the soluble form (sVAP-1) accounts for most circulating monoamine oxidase activity, has insulin-like effects, and can initiate oxidative stress. Here, we determined that hepatic VAP-1 expression is increased in patients with chronic liver disease and that serum sVAP-1 levels are elevated in patients with NAFLD compared with those in control individuals. In 4 murine hepatic injury models, an absence or blockade of functional VAP-1 reduced inflammatory cell recruitment to the liver and attenuated fibrosis. Moreover, disease was reduced in animals expressing a catalytically inactive form of VAP-1, implicating enzyme activity in the disease pathogenesis. Within the liver, hepatic stromal cells expressed functional VAP-1, and evaluation of cultured cells revealed that sVAP-1 promotes leukocyte migration through catalytic generation of ROS, which depended on VAP-1 enzyme activity. VAP-1 enhanced stromal cell spreading and wound closure and modulated expression of profibrotic genes. Together, these results link the amine oxidase activity of VAP-1 with hepatic inflammation and fibrosis and suggest that targeting VAP-1 has therapeutic potential for NAFLD and other chronic fibrotic liver diseases.
Bone mass loss in chronic heart failure is associated with secondary hyperparathyroidism and has prognostic significance
Authors: John Terrovitis, Panagiotis Zotos, Elissavet Kaldara, Nikolaos Diakos, Eleni Tseliou, Stella Vakrou, Chris Kapelios, Athanasios Chalazonitis, Serafeim Nanas, Savas Toumanidis, Dimitrios Kontoyannis, Eleni Karga, John Nanas
Journal: European Journal of Heart Failure (2012)
Biobank research: who benefits from individual consent?
Authors: J. Stjernschantz Forsberg, M. G. Hansson, S. Eriksson
Journal: BMJ (2011)

Requiring informed consent for research on stored tissue samples and associated data safeguards the autonomy rights of donors. But <b>Joanna Stjernschantz Forsberg</b>, <b>Mats Hansson</b>, and <b>Stefan Eriksson</b> argue that this policy not only defeats the interest of society but also runs counter to the interests of the individuals it purports to protect
Relationship Between Long Durations and Different Regimens of Hormone Therapy and Risk of Breast Cancer
Authors: Christopher I. Li, Kathleen E. Malone, Peggy L. Porter, Noel S. Weiss, Mei Tzu C Tang, Kara L. Cushing-Haugen, Janet R. Daling
Journal: JAMA (2003)

HERE IS CONSIDERABLE EVIdence from observational studies, 1 and now from a randomized controlled trial, the Women's Health Initiative (WHI), 2 that use of combined estrogen and progestin hormone replacement therapy (CHRT) is associated with an increased risk of breast cancer.Specifically, a pooled analysis of 51 observational studies found that current users of CHRT or progestin alone for 5 years or longer had a 53% increase in risk of breast cancer, 1 and after 5.2 years of follow-up the WHI reported that CHRT was associated with a statistically nonsignificant 26% increase in breast cancer risk. 2 However, few studies have evaluated the effects of very long durations (Ն15 years) of CHRT use on breast cancer risk.Two studies found that use of CHRT for 5 years or longer was associated with an increased risk of breast cancer (although use for 10 years or longer did not further increase the magnitude of these risks), 3,4 but another reported that only use of CHRT for 10 years or longer was associated with an increase in risk. 5Also, the WHI evaluated use of the progestin component of CHRT in a continuous (daily) manner, and thus its results may not pertain to other patterns of CHRT use.
Glutamic Acid, the Main Dietary Amino Acid, and Blood Pressure
Authors: Jeremiah Stamler, Ian J. Brown, Martha L. Daviglus, Queenie Chan, Hugo Kesteloot, Hirotsugu Ueshima, Liancheng Zhao, Paul Elliott
Journal: Circulation (2009)

Data are available that indicate an independent inverse relationship of dietary vegetable protein to the blood pressure (BP) of individuals. Here, we assess whether BP is associated with glutamic acid intake (the predominant dietary amino acid, especially in vegetable protein) and with each of 4 other amino acids that are relatively higher in vegetable than animal protein (proline, phenylalanine, serine, and cystine).