tbuckley/cabot-search huggingface dataset:
Identification of Novel Gene Amplifications in Breast Cancer and Coexistence of Gene Amplification with an Activating Mutation of <i>PIK3CA</i>
Authors: Mitsutaka Kadota, Misako Sato, Beverly Duncan, Akira Ooshima, Howard H. Yang, Natacha Diaz-Meyer, Sheryl Gere, Shun-Ichiro Kageyama, Junya Fukuoka, Takuya Nagata, Kazuhiro Tsukada, Barbara K. Dunn, Lalage M. Wakefield, Maxwell P. Lee
Journal: Cancer Research (2009)

To identify genetic events that characterize cancer progression, we conducted a comprehensive genetic evaluation of 161 primary breast tumors. Similar to the "mountain-and-hill" view of mutations, gene amplification also shows high- and low-frequency alterations in breast cancers. The frequently amplified genes include the well-known oncogenes ERBB2, FGFR1, MYC, CCND1, and PIK3CA, whereas other known oncogenes that are amplified, although less frequently, include CCND2, EGFR, FGFR2, and NOTCH3. More importantly, by honing in on minimally amplified regions containing three or fewer genes, we identified six new amplified genes: POLD3, IRAK4, IRX2, TBL1XR1, ASPH, and BRD4. We found that both the IRX2 and TBL1XR1 proteins showed higher expression in the malignant cell lines MCF10CA1h and MCF10CA1a than in their precursor, MCF10A, a normal immortalized mammary epithelial cell line. To study oncogenic roles of TBL1XR1, we performed knockdown experiments using a short hairpin RNA approach and found that depletion of TBL1XR1 in MCF10CA1h cells resulted in reduction of cell migration and invasion as well as suppression of tumorigenesis in mouse xenografts. Intriguingly, our mutation analysis showed the presence of activation mutations in the PIK3CA gene in a subset of tumors that also had DNA copy number increases in the PIK3CA locus, suggesting an additive effect of coexisting activating amino acid substitution and dosage increase from amplification. Our gene amplification and somatic mutation analysis of breast primary tumors provides a coherent picture of genetic events, both corroborating and novel, offering insight into the genetic underpinnings of breast cancer progression.
Baseline factors influencing decisions on digital follow-up of melanocytic lesions in daily practice: An Italian multicenter survey
Authors: Paolo Carli, Giovanni Ghigliotti, Matteo Gnone, Alessandra Chiarugi, Emanuele Crocetti, Stefano Astorino, Ugo A. Berti, Paolo Broganelli, Antonio Carcaterra, Maria Teresa Corradin, Giovanni Pellacani, Domenico Piccolo, Massimiliano Risulo, Ignazio Stanganelli, Vincenzo De Giorgi
Journal: Journal of the American Academy of Dermatology (2006)
Inhibition of gastric acid secretion in the dog by the H2-receptor antagonists, ranitidine, cimetidine, and metiamide.
Authors: M J Daly, J M Humphray, R Stables
Journal: Gut (1980)

The new H2-receptor antagonist, ranitidine, has been compared with cimetidine and metiamide as an inhibitor of gastric acid secretion in the dog. All three compounds were effective both intravenously or by mouth in inhibiting secretion induced by histamine, pentagastrin, or bethanechol. This inhibition was mainly attributable to a reduction in the volume of secretion, although there was also a significant reduction in the concentration of acid secreted. Metiamide was slightly less active than cimetidine, but ranitidine was four to nine times more potent than cimetidine, depending on the secretagogue used. The antisecretory activity of ranitidine does not result from a limitation in blood flow to the gastric mucosa.
Progress towards the comprehensive control of hepatitis B in Africa: a view from South Africa.
Authors: M C Kew
Journal: Gut (1996)

The carrier rate of hepatitis B virus (HBV) in black Africans averages 10.4% throughout the continent. Even within each country, however, there may be wide variations. HBV carriage in black Africans is largely established in early childhood, mostly through horizontal transmission. Perinatal transmission also occurs but to a much lesser extent than in the Far East. For unknown reasons, HBeAg positivity rates are much lower in black Africans of childbearing age than in women in the Far East. Universal HBV vaccination of infants in South Africa started in April 1995. Effective integration into the Expanded Programme on Vaccination will probably be necessary if administration of second and third doses is to be ensured. Fortunately, a natural process of urbanisation is also having a beneficial effect on the black carrier rate in South Africa, as urban carrier rates tend to be much lower than those in rural area. Within the next 20 years, therefore, there should be a great reduction in the numbers of acute HBV infections and new carriers. However, it will take much longer before there is any substantial impact on the burden of the longterm sequelae of HBV infection--that is, cirrhosis and hepatocellular carcinoma.
Baroreceptor Reflexes and Autoregulation of Cerebral Blood Flow in the Dog
Authors: CARLOS E. RAPELA, HAROLD D. GREEN, ADAM B. DENISON
Journal: Circulation Research (1967)

Cerebral venous outflow was measured in anesthetized dogs at the confluence of the sagittal and straight sinuses, with the lateral sinuses occluded. Denervation of the carotid bifurcation increased systemic arterial pressure (+25.8; SE ±7.7 mm Hg) and decreased cerebral vascular conductance (-0.018; SE ±0.005 ml/min · mm Hg); stimulation of the carotid sinus nerve decreased systemic arterial pressure and increased cerebral vascular conductance. Graded constrictions of the common carotid arteries induced transient responses of the cerebral blood flow that were characteristic of an autoregulatory process. Plots of the steady-state pressures and flows during the decreases of perfusion pressure were concave toward the pressure axis, were similar before and after denervation of the carotid bifurcation, and were indicative of autoregulation. We conclude that pressoreceptors in the carotid bifurcation or other pressoreceptors in systemic vessels upstream from the carotid bifurcation are not necessary for the control of the "tone" of the cerebral vasculature or in the mechanism of the autoregulation of cerebral blood flow.
Analysis of Host–Parasite Incongruence in Papillomavirus Evolution Using Importance Sampling
Authors: Seena D. Shah, John Doorbar, Richard A. Goldstein
Journal: Molecular Biology and Evolution (2010)

The papillomaviruses (PVs) are a family of viruses infecting several mammalian and nonmammalian species that cause cervical cancer in humans. The evolutionary history of the PVs as it associated with a wide range of host species is not well understood. Incongruities between the phylogenetic trees of various viral genes as well as between these genes and the host phylogenies suggest historical viral recombination as well as violations of strict virus–host cospeciation. The extent of recombination events among PVs is uncertain, however, and there is little evidence to support a theory of PV spread via recent host transfers. We have investigated incongruence between PV genes and hence, the possibility of recombination, using Bayesian phylogenetic methods. We find significant evidence for phylogenetic incongruence among the six PV genes E1, E2, E6, E7, L1, and L2, indicating substantial recombination. Analysis of E1 and L1 phylogenies suggests ancestral recombination events. We also describe a new method for examining alternative host–parasite association mechanisms by applying importance sampling to Bayesian divergence time estimation. This new approach is not restricted by a fixed viral tree topology or knowledge of viral divergence times, multiple parasite taxa per host may be included, and it can distinguish between prior divergence of the virus before host speciation and host transfer of the virus following speciation. Using this method, we find prior divergence of PV lineages associated with the ancestral mammalian host resulting in at least 6 PV lineages prior to speciation of this host. These PV lineages have then followed paths of prior divergence and cospeciation to eventually become associated with the extant host species. Only one significant instance of host transfer is supported, the transfer of the ancestral L1 gene between a Primate and Hystricognathi host based on the divergence times between the υ human type 41 and porcupine PVs.
Oral Tolerance: Immunologic Mechanisms and Treatment of Animal and Human Organ-Specific Autoimmune Diseases by Oral Administration of Autoantigens
Authors: H L Weiner, A Friedman, A Miller, S J Khoury, A al-Sabbagh, L Santos, M Sayegh, R B Nussenblatt, D E Trentham, D A Hafler
Journal: Annual Review of Immunology (1994)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies.
Authors: Z S Pavletic, M R Bishop, S R Tarantolo, S Martin-Algarra, P J Bierman, J M Vose, E C Reed, T G Gross, J Kollath, K Nasrati, J D Jackson, J O Armitage, A Kessinger
Journal: Journal of Clinical Oncology (1997)

PURPOSE To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared with 22 identically treated historical patients who received allogeneic BMT. RESULTS The median infused CD34+ cell and granulocyte-macrophage colony-forming unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The median time to a neutrophil count greater than 500/ microL was 11 days after BSC and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC recovery after BSC was observed. BSC patients received fewer platelet transfusions: 10 versus 19 (P = .015). The median length of hospitalization was shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT, respectively (P = .4654). CONCLUSION In comparison to BMT, allogeneic BSC transplantation may result in faster hematopoietic recovery, shorter hospital stay, and similar early survival. Whether allogeneic BSC are superior to bone marrow needs to be determined in randomized trials.
Inhibition of Periostin Expression Protects against the Development of Renal Inflammation and Fibrosis
Authors: Mouna Mael-Ainin, Ahmed Abed, Simon J. Conway, Jean-Claude Dussaule, Christos Chatziantoniou
Journal: Journal of the American Society of Nephrology (2014)

Increased renal expression of periostin, a protein normally involved in embryonic and dental development, correlates with the decline of renal function in experimental models and patient biopsies. Because periostin has been reported to induce cell differentiation, we investigated whether it is also involved in the development of renal disease and whether blocking its abnormal expression improves renal function and/or structure. After unilateral ureteral obstruction in wild-type mice, we observed a progressive increase in the expression and synthesis of periostin in the obstructed kidney that associated with the progression of renal lesions. In contrast, mice lacking the periostin gene showed less injury-induced interstitial fibrosis and inflammation and were protected against structural alterations. This protection was associated with a preservation of the renal epithelial phenotype. In vitro, administration of TGF-β to renal epithelial cells increased the expression of periostin several-fold, leading to subsequent loss of the epithelial phenotype. Furthermore, treatment of these cells with periostin increased the expression of collagen I and stimulated the phosphorylation of FAK, p38, and ERK 42/44. In vivo delivery of antisense oligonucleotides to inhibit periostin expression protected animals from L-NAME–induced renal injury. These data strongly suggest that periostin mediates renal disease in response to TGF-β and that blocking periostin may be a promising therapeutic strategy against the development of CKD.
The Adult Mouse Anatomical Dictionary: a tool for annotating and integrating data.
Authors: Terry F Hayamizu, Mary Mangan, John P Corradi, James A Kadin, Martin Ringwald
Journal: Genome biology (2005)

Abstract We have developed an ontology to provide standardized nomenclature for anatomical terms in the postnatal mouse. The Adult Mouse Anatomical Dictionary is structured as a directed acyclic graph, and is organized hierarchically both spatially and functionally. The ontology will be used to annotate and integrate different types of data pertinent to anatomy, such as gene expression patterns and phenotype information, which will contribute to an integrated description of biological phenomena in the mouse.
Role of the Baroreceptor Reflex in Daily Control of Arterial Blood Pressure and Other Variables in Dogs
Authors: ALLEN W. COWLEY, JEAN FRANCOIS LIARD, ARTHUR C. GUYTON
Journal: Circulation Research (1973)

Normal and sinoaortic baroreceptor-denervated dogs were monitored continuously (24 hours a day) to quantify the role of the baroreceptors in determining the average level and the variability of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance. The frequency of occurrence over 24-hour periods was obtained for each variable using a fiber optic curve-scanning system to read the variables from continuously recorded charts and a digital computer system to plot curves. The results indicate that the degree of hypertension previously reported for this preparation has been highly exaggerated, presumably due to the methods of study. The average 24-hour mean arterial blood pressure was 101.6 mm Hg in normal dogs and only 112.7 mm Hg in baroreceptor-denervated dogs. The normal dogs exhibited narrowly distributed 24-hour frequency distribution curves for blood pressure; in contrast the denervated dogs exhibited curves with twice the 24-hour standard deviation. Similar analysis indicated that the baroreceptors exerted less influence on the daily stabilization of heart rate than they did on arterial blood pressure and that they had very little if any influence on the daily stabilization of cardiac output and total peripheral resistance. Hemodynamic variables during postural changes were studied along with diurnal rhythms. We concluded that the primary function of the baroreceptor reflex is not to set the chronic level of arterial blood pressure but, instead, to minimize variations in systemic arterial blood pressure, whether these variations are caused by postural changes of the animal, excitement, diurnal rhythm, or even spontaneous fluctuations of unknown origin.
ARE IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR SHOCKS PROARRHYTHMIC? IMPACT OF LEFT VENTRICULAR FUNCTION, ETIOLOGY OF CARDIOMYOPATHY, SHOCK SYNCHRONIZATION AND ARRHYTHMIA FEATURES
Authors: Amit V. Patel, Anshuman Das, Amit K. Mehrotra, Joshua Moss, Hemal Nayak
Journal: Journal of the American College of Cardiology (2013)
Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction.
Authors: D J Fitzgerald, F Catella, L Roy, G A FitzGerald
Journal: Circulation (1988)

We assessed thromboxane biosynthesis as an index of platelet activation in 6 patients with acute myocardial infarction receiving intravenous streptokinase. Urinary 2,3-dinor-thromboxane B2 and plasma 11-dehydro-thromboxane B2, major enzymatic metabolites of thromboxane A2, were markedly increased after intravenous streptokinase (11,063 +/- 2758 pg/mg creatinine and 33 +/- 10 pg/ml, respectively) compared with levels in patients not receiving thrombolytic therapy (502 +/- 89 pg/mg creatinine and 3 +/- 0.7 pg/ml). Prostacyclin biosynthesis also increased markedly after streptokinase coincident with the increase in thromboxane A2 formation. Administration of aspirin between the time of onset of coronary thrombosis and reperfusion both in man and in a canine preparation demonstrated that this reflected thromboxane biosynthesis de novo and not metabolism of preformed inactive thromboxane B2 washed out from the coronary circulation. Since the platelet is the major source of thromboxane A2, these findings suggest that there is marked platelet activation after coronary thrombolysis with streptokinase. Studies in vitro demonstrated that streptokinase enhanced platelet activation in a dose-dependent manner, resulting in the secondary release of thromboxane A2. The increase in platelet activation and thromboxane A2 biosynthesis may limit the therapeutic effect of intravenous streptokinase in acute myocardial infarction.
651 THE MORTALITY AND COMPLICATION RATES OF HEPATECTOMY, RADIOFREQUENCY ABLATION, AND TRANS-CATHETER ARTERIAL EMBOLIZATION FOR LIVER TUMORS: ANALYSIS OF JAPANESE NATIONWIDE DATABASE
Authors: M. Sato, R. Tateishi, H. Yasunaga, H. Horiguchi, H. Yoshida, S. Matsuda, K. Koike
Journal: Journal of Hepatology (2011)
Effect of Ischemia and Antianginal Drugs on the Distribution of Radioactive Microspheres in the Canine Left Ventricle
Authors: LEWIS C. BECKER, NICHOLAS J. FORTUIN, BERTRAM PITT
Journal: Circulation Research (1971)

Radioactive microspheres were used to estimate the changes in regional myocardial blood flow occurring during acute myocardial ischemia. Carbonized 15-µ spheres were injected into the left atrium of 28 open-chest dogs and the radioactivity of selected areas determined after sacrifice. Acute occlusion of the left circumflex coronary artery produced a significant diminution in the proportion of microspheres reaching the circumflex area. In addition, there was a disproportionate decrease in endocardial radioactivity in the ischemic area (endocardial/epicardial radioactivity ratio falling from 1.17 to 0.76, P &lt; 0.001) but not in the nonischemic area. Both nitroglycerin (0.4 mg) and propranolol (1 mg/kg) failed to cause a significant change in the ratio of circumflex to descendens radioactivity during ischemia. They did, however, cause a significant increase in the ratio of endocardial to epicardial radioactivity in both ischemic and nonischemic areas.
Coronary Artery Disease and Carotid Artery Intima-Media Thickness in Japanese Type 2 Diabetic Patients
Authors: Naomi Mitsuhashi, Tomio Onuma, Sayaka Kubo, Naoko Takayanagi, Motoe Honda, Ryuzo Kawamori
Journal: Diabetes Care (2002)

To investigate the association between carotid atherosclerosis, measured as intima-media thickness (IMT), and cardiovascular morbidity in type 2 diabetic patients.We investigated the relationship between IMT and coronary artery disease (CAD) in 40 type 2 diabetic patients and 40 control subjects. Diabetic patients with CAD determined by coronary angiography were consecutively recruited, whereas the control subjects were recruited from among diabetic outpatients without CAD at the same institution. IMT was measured in both carotid arteries using B-mode ultrasonography.Carotid IMT was significantly greater in the diabetic patients than in the control subjects (1.27 +/- 0.07 vs. 1.03 +/- 0.04 mm, P < 0.05). IMT was associated with CAD by logistic regression analysis using all independent variables (P = 0.062). When the 40 patients with CAD were divided into a group of 20 patients with coronary artery bypass grafting (CABG) and another 20 patients without CABG, the IMT was significantly greater in the CABG group than in the non-CABG group (1.47 +/- 0.11 vs. 1.07 +/- 0.07 mm, P < 0.05).These results indicate that the presence of carotid atherosclerosis implies a high probability of coronary involvement in Japanese nonobese subjects with type 2 diabetes.
A Randomized Trial of Exemestane after Two to Three Years of Tamoxifen Therapy in Postmenopausal Women with Primary Breast Cancer
Authors: R. Charles Coombes, Emma Hall, Lorna J. Gibson, Robert Paridaens, Jacek Jassem, Thierry Delozier, Stephen E. Jones, Isabel Alvarez, Gianfilippo Bertelli, Olaf Ortmann, Alan S. Coates, Emilio Bajetta, David Dodwell, Robert E. Coleman, Lesley J. Fallowfield, Elizabeth Mickiewicz, Jorn Andersen, Per E. Lønning, Giorgio Cocconi, Alan Stewart, Nick Stuart, Claire F. Snowdon, Marina Carpentieri, Giorgio Massimini, Judith M. Bliss
Journal: New England Journal of Medicine (2004)

Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse.We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival.Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported--183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04).Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.
Genome-Wide Single Nucleotide Polymorphism Analysis Reveals Frequent Partial Uniparental Disomy Due to Somatic Recombination in Acute Myeloid Leukemias
Authors: Manoj Raghavan, Debra M. Lillington, Spyros Skoulakis, Silvana Debernardi, Tracy Chaplin, Nicola J. Foot, T. Andrew Lister, Bryan D. Young
Journal: Cancer Research (2005)

Genome-wide analysis of single nucleotide polymorphisms in 64 acute myeloid leukemias has revealed that approximately 20% exhibited large regions of homozygosity that could not be accounted for by visible chromosomal abnormalities in the karyotype. Further analysis confirmed that these patterns were due to partial uniparental disomy (UPD). Remission bone marrow was available from five patients showing UPD in their leukemias, and in all cases the homozygosity was found to be restricted to the leukemic clone. Two examples of UPD11p were shown to be of different parental origin as indicated by the methylation pattern of the H19 gene. Furthermore, a previously identified homozygous mutation in the CEBPA gene coincided with a large-scale UPD on chromosome 19. These cryptic chromosomal abnormalities, which seem to be nonrandom, have the characteristics of somatic recombination events and may define an important new subclass of leukemia.