tbuckley/cabot-search huggingface dataset:
Horizontal transmission, vertical inactivation, and stochastic loss of mariner-like transposable elements.
Authors: A. R. Lohe, E. N. Moriyama, D. A. Lidholm, D. L. Hartl
Journal: Molecular Biology and Evolution (1995)

Horizontal transmission has been well documented as a major mechanism for the dissemination of mariner-like elements (MLEs) among species. Less well understood are mechanisms that limit vertical transmission of MLEs resulting in the "spotty" or discontinuous distribution observed in closely related species. In this article we present evidence that the genome of the common ancestor of the melanogaster species subgroup of Drosophila contained an MLE related to the mellifera (honey bee) subfamily. Horizontal transmission, approximately 3-10 MYA, is strongly suggested by the observation that the sequence of the MLE in Drosophila erecta is 97% identical in nucleotide sequence with that of an MLE in the cat flea, Ctenocephalides felis. The D. erecta MLE has a spotty distribution among species in the melanogaster subgroup. The element has a high copy number in D. erecta and D. orena, a moderate copy number in D. teissieri and D. yakuba, and was apparently lost ("stochastic loss") in the lineage leading to D. melanogaster, D. simulans, D. mauritiana, and D. sechellia. In D. erecta, most copies are concentrated in the heterochromatin. Two copies from D. erecta, denoted De12 and De19, were cloned and sequenced, and they appear to be nonfunctional ("vertical inactivation"). It therefore appears that the predominant mode of MLE evolution is vertical inactivation and stochastic loss balanced against occasional reinvasion of lineages by horizontal transmission.
Arrhythmias in the Athlete With Congenital Heart Disease: Guidelines For Participation
Authors: Richard R. Liberthson, MD
Journal: Annual Review of Medicine (1999)

Advances in the diagnosis and early management of congenital heart disease in recent decades have led to increasing numbers of individuals being sufficiently well to participate in social as well as truly competitive sports. Physicians are increasingly asked whether such participation is safe, advisable, and efficacious, yet few guidelines exist to help them make these decisions. There are three apparent subgroups of patients: (a) those with mild or repaired problems, who function normally or nearly so and may fully participate; (b) those with severe functional deficit or known high risk, for whom strenuous exertion must be strictly proscribed; and (c) those who fall in between, with some limitations and some risk--these patients present a great challenge to the wisdom and clinical skill of the physician.
Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I
Authors: Alice Pievani, Isabella Azario, Laura Antolini, Tsutomu Shimada, Pravin Patel, Cristina Remoli, Benedetta Rambaldi, Maria Grazia Valsecchi, Mara Riminucci, Andrea Biondi, Shunji Tomatsu, Marta Serafini
Journal: Blood (2014)
Role of induction chemotherapy and bone marrow transplantation in adult lymphoblastic lymphoma: A report on 62 patients from a single center
Authors: R. Bouabdallah, L. Xerri, V.-J. Bardou, A.-M. Stoppa, D. Blaise, D. Sainty, D. Maraninchi, J.-A. Gastaut
Journal: Annals of Oncology (1998)
Review of Adverse Events Associated With False Glucose Readings Measured by GDH-PQQ–Based Glucose Test Strips in the Presence of Interfering Sugars
Authors: Juan P. Frias, Christine G. Lim, John M. Ellison, Carol M. Montandon
Journal: Diabetes Care (2010)

To assess the implications of falsely elevated glucose readings measured with glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) test strips.We conducted a review of the Food and Drug Administration's Manufacturer and User Facility Device Experience database and medical literature for adverse events (AEs) associated with falsely elevated glucose readings with GDH-PQQ test strips in the presence of interfering sugars.Eighty-two reports were identified: 16 (20%) were associated with death, 46 (56%) with severe hypoglycemia, and 12 (15%) with nonsevere hypoglycemia. In eight reports (10%), the AE was not described. Forty-two events (51%) occurred in the U.S. Although most events occurred in hospitalized patients, at least 14 (17%) occurred in outpatients. Agents most commonly associated with AEs were icodextrin-containing peritoneal dialysate and maltose-containing intravenous immune globulin.GDH-PQQ test strips pose a safety risk to insulin-using patients treated with agents containing or metabolized to interfering sugars.
Challenges in Systematic Reviews That Assess Treatment Harms
Authors: Roger Chou, Mark Helfand
Journal: Annals of Internal Medicine (2005)

An evidence synthesis of a medical intervention should assess the balance of benefits and harms. Investigators performing systematic reviews of harms face challenges in finding data, rating the quality of harms reporting, and synthesizing and displaying data from different sources. Systematic reviews of harms often rely primarily on published clinical trials. Identifying important harms of treatment and quantifyi ng the risk associated with them, however, often require a broader range of data sources, including unpublished trials, observational studies, and unpublished information on published trials submitted to the U.S. Food and Drug Administration. Each source of data has some potential for yielding important information. Criteria for judging the quality of harms assessment and reporting are still in their early stages of development. Investigators conducting systematic reviews of harms should consider empirically validating the criteria they use to judge the validity of studies reporting harms. Synthesizing harms data from different sources requires careful consideration of internal validity, applicability, and sources of heterogeneity. This article highlights examples of approaches to methodologic issues associated with performing systematic reviews of harms from 96 Evidence-based Practice Center evidence reports.
Angiographic validation of bedside markers of coronary reperfusion in acute myocardial infarction; can unnecessary emergency angioplasties be reduced? A prospective study
Authors: T.J.M.Oude Ophuls, F.W. Bär, W.J. Janssen, F. Vermoor, W.R.M. Dassen, H.J.J. Wellens
Journal: Journal of the American College of Cardiology (1998)
<i>IKZF1</i>(Ikaros) Deletions in<i>BCR-ABL1</i>–Positive Acute Lymphoblastic Leukemia Are Associated With Short Disease-Free Survival and High Rate of Cumulative Incidence of Relapse: A GIMEMA AL WP Report
Authors: Giovanni Martinelli, Ilaria Iacobucci, Clelia Tiziana Storlazzi, Marco Vignetti, Francesca Paoloni, Daniela Cilloni, Simona Soverini, Antonella Vitale, Sabina Chiaretti, Giuseppe Cimino, Cristina Papayannidis, Stefania Paolini, Loredana Elia, Paola Fazi, Giovanna Meloni, Sergio Amadori, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Robin Foà
Journal: Journal of Clinical Oncology (2009)

Purpose The causes of the aggressive nature of BCR-ABL1–positive adult acute lymphoblastic leukemia (ALL) are unknown. To identify, at the submicroscopic level, oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed an investigation of genomic copy number alterations using single nucleotide polymorphism array, genomic polymerase chain reaction, and sequencing of candidate genes. Patients and Methods Eighty-three patients with de novo adult Philadelphia chromosome (Ph) –positive ALL were enrolled onto institutional (n = 17) or Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Working Party delle Leucemia Acute (n = 66) clinical trials. Treatments included tyrosine kinase inhibitor (TKI) alone, conventional chemotherapy, or a combination of TKI and chemotherapy. Results A 7p12 deletion of IKZF1 (Ikaros) was identified in 52 (63%) of 83 patients. The pattern of deletion varied among different patients, but the two most common deletion types were loss of exons 4 to 7 in 31 (37%) of 83 patients and loss of exons 2 to 7 in 17 (20%) of 83 patients. Disease-free survival (DFS) was shorter in patients with IKZF1 deletion versus patients with IKZF1 wild type (10 v 32 months, respectively; P = .02). Furthermore, a significantly shorter cumulative incidence of relapse was recorded in patients with IKZF1 deletion versus patients with IKZF1 wild type (10.1 v 56.1 months, respectively; P = .001). Multivariate analysis confirmed the negative prognostic impact of IKZF1 deletion on DFS (P = .04). Conclusion We conclude that IKZF1 deletions are likely to be a genomic alteration that significantly affects the prognosis of Ph-positive ALL in adults.
Within-breath changes of respiratory impedance in COPD and healthy adults
Authors: András Lorx, Dóra Bartusek, Szabolcs Szigeti, Réka Stein-Udvardi, Ádám Bálint, János Gál, György Losonczy, Peter Sly, Zoltán Hantos
Journal: European Respiratory Journal (2013)

Reduction of respiratory system reactance (Xrs) in expiration indicates expiratory flow limitation in COPD patients (Dellaca et al., Eur Respir J, 23: 232, 2004). The aim of our study was to determine within-breath changes in respiratory resistance (Rrs) and Xrs, as functions of tidal flow (V’) and volume (V).  Forced oscillations at 8 Hz were superimposed on quiet breathing in 44 COPD (GOLD III and IV) patients and 13 control subjects (C), and Rrs and Xrs estimated every 1/8 s. Values of Rrs and Xrs were compared at their extremes (min and max), values at minimum (vmin) and maximum volume (vmax), maximum inspiratory (ifmax) and expiratory flow (efmax), and the area of the Xrs vs V loop normalized for V (AXrs).  Strong dependence of Rrs and Xrs on V’ and V were observed in all subjects but with markedly different loop patterns in the two groups.  The differences between COPD and C were highly significant in the group median values of AXrs (4.2 vs 0.5 hPa.s/l), Xrs(min) (-9.8 vs -2.1 hPa.s/l), Xrs(vmin) (-4.7 vs -0.5 hPa.s/l), and Xrs(efmax) (-4.8 vs -0.4 hPa.s/l), Rrs(ifmax) (5.1 vs 3.9 hPa.s/l), all P  Tracking of oscillatory impedance can be accomplished easily with minimum demand for cooperation and no complex respiratory manoeuvres, and reveals characteristic within-breath changes in airway size and rheology. The development of flow limitation is seen in COPD.
Statistical Treatment of Exacerbations in Therapeutic Trials of Chronic Obstructive Pulmonary Disease
Authors: Samy Suissa
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Section:ChooseTop of pageAbstract <<APPROACHES TO DATA ANALYS...ILLUSTRATIONRESULTS OF ILLUSTRATIONDISCUSSIONReferencesCITING ARTICLES
Ischemic Mitral Regurgitation
Authors: Francesco Grigioni, Maurice Enriquez-Sarano, Kenton J. Zehr, Kent R. Bailey, A. Jamil Tajik
Journal: Circulation (2001)

Myocardial infarction (MI) can directly cause ischemic mitral regurgitation (IMR), which has been touted as an indicator of poor prognosis in acute and early phases after MI. However, in the chronic post-MI phase, prognostic implications of IMR presence and degree are poorly defined.We analyzed 303 patients with previous (>16 days) Q-wave MI by ECG who underwent transthoracic echocardiography: 194 with IMR quantitatively assessed in routine practice and 109 without IMR matched for baseline age (71+/-11 versus 70+/-9 years, P=0.20), sex, and ejection fraction (EF, 33+/-14% versus 34+/-11%, P=0.14). In IMR patients, regurgitant volume (RVol) and effective regurgitant orifice (ERO) area were 36+/-24 mL/beat and 21+/-12 mm(2), respectively. After 5 years, total mortality and cardiac mortality for patients with IMR (62+/-5% and 50+/-6%, respectively) were higher than for those without IMR (39+/-6% and 30+/-5%, respectively) (both P<0.001). In multivariate analysis, independently of all baseline characteristics, particularly age and EF, the adjusted relative risks of total and cardiac mortality associated with the presence of IMR (1.88, P=0.003 and 1.83, P=0.014, respectively) and quantified degree of IMR defined by RVol >/=30 mL (2.05, P=0.002 and 2.01, P=0.009) and by ERO >/=20 mm(2) (2.23, P=0.003 and 2.38, P=0.004) were high.In the chronic phase after MI, IMR presence is associated with excess mortality independently of baseline characteristics and degree of ventricular dysfunction. The mortality risk is related directly to the degree of IMR as defined by ERO and RVol. Therefore, IMR detection and quantification provide major information for risk stratification and clinical decision making in the chronic post-MI phase.
Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome
Authors: Daniel P. Judge, Nancy J. Biery, Douglas R. Keene, Jessica Geubtner, Loretha Myers, David L. Huso, Lynn Y. Sakai, Harry C. Dietz
Journal: Journal of Clinical Investigation (2004)

Marfan syndrome is a connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1). A dominant-negative mechanism has been inferred based upon dominant inheritance, mulitimerization of monomers to form microfibrils, and the dramatic paucity of matrix-incorporated fibrillin-1 seen in heterozygous patient samples. Yeast artificial chromosome–based transgenesis was used to overexpress a disease-associated mutant form of human fibrillin-1 (C1663R) on a normal mouse background. Remarkably, these mice failed to show any abnormalities of cellular or clinical phenotype despite regulated overexpression of mutant protein in relevant tissues and developmental stages and direct evidence that mouse and human fibrillin-1 interact with high efficiency. Immunostaining with a human-specific mAb provides what we believe to be the first demonstration that mutant fibrillin-1 can participate in productive microfibrillar assembly. Informatively, use of homologous recombination to generate mice heterozygous for a comparable missense mutation (C1039G) revealed impaired microfibrillar deposition, skeletal deformity, and progressive deterioration of aortic wall architecture, comparable to characteristics of the human condition. These data are consistent with a model that invokes haploinsufficiency for WT fibrillin-1, rather than production of mutant protein, as the primary determinant of failed microfibrillar assembly. In keeping with this model, introduction of a WT FBN1 transgene on a heterozygous C1039G background rescues aortic phenotype.
Meta-Analysis: Pharmacologic Treatment of Obesity
Authors: Zhaoping Li, Margaret Maglione, Wenli Tu, Walter Mojica, David Arterburn, Lisa R. Shugarman, Lara Hilton, Marika Suttorp, Vanessa Solomon, Paul G. Shekelle, Sally C. Morton
Journal: Annals of Internal Medicine (2005)

Background: In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used. Purpose: To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss. Data Sources: Electronic databases, experts in the field, and unpublished information. Study Selection: Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively. Data Extraction: The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication. Data Synthesis: All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% CI, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (CI, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (CI, −1.6 to 11.5 kg) for diethylpropion-treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (CI, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (CI, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported. Limitations: Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all meta-analyses. Conclusions: Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs.
Components of the "Central" Blood Volume in the Dog
Authors: ROBERT J. MARSHALL, YANG WANG, JOHN T. SHEPHERD
Journal: Circulation Research (1960)

The indicator-dilution method was used in the dog in an attempt to define the proportion of the "central" blood volume contained in the lung vessels. When injections were made into the pulmonary artery with sampling from the femoral artery only half or even less of the calculated blood volume could be accounted for by the lungs. When a venous injection site was used, the proportion in the lungs was reduced to a third or less. Thus when peripheral sites are used for the inscription of indicator-dilution curves few deductions can be made about either the actual volume or even relative changes in the volume of blood in the lungs.
Abstract C65: Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44+ cells and evidence for epigenetic mechanisms
Authors: Xin Chen, Izabela Fokt, Stanislaw Skora, Waldemar Priebe, Yongyi Bi, Dean G. Tang, Hong Yan, Qiuping Zhang, Jichao Qin, Hangwen Li, Can Liu, Tammy Davis, Luis D. Coletta, Jim Klostergaard
Journal: Cancer Research (2012)

Abstract Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even nontumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44+ cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many ‘stemness’ genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44+ tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms. Citation Format: Xin Chen, Izabela Fokt, Stanislaw Skora, Waldemar Priebe, Yongyi Bi, Dean G. Tang, Hong Yan, Qiuping Zhang, Jichao Qin, Hangwen Li, Can Liu, Tammy Davis, Luis D. Coletta, Jim Klostergaard. Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44+ cells and evidence for epigenetic mechanisms [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C65.
Mutations Within the Kinase Domain and Truncations of the Epidermal Growth Factor Receptor Are Rare Events in Bladder Cancer: Implications for Therapy
Authors: Kelly N. Blehm, Philippe E. Spiess, Jolanta E. Bondaruk, Melanie E. Dujka, Gabriel J. Villares, Yi-jue Zhao, Oliver Bogler, Kenneth D. Aldape, H. Barton Grossman, Liana Adam, David J. McConkey, Bogdan A. Czerniak, Colin P. Dinney, Menashe Bar-Eli
Journal: Clinical Cancer Research (2006)

Abstract Purpose: It has previously been reported that the patient response to gefitinib depends on the presence of mutations within the kinase domain of epidermal growth factor receptor (EGFR) or the expression of its truncated form, EGFR variant III (EGFRvIII). The focus of this study was to determine if these alterations are present within the tyrosine kinase and ligand-binding domain of EGFR in urothelial carcinoma. Experimental Design: The kinase domain found within exons 18 to 21 of the EGFR from 11 bladder cancer cell lines and 75 patient tumors were subjected to automated sequencing. EGFRvIII expression was determined by immunohistochemistry using a urothelial carcinoma tissue microarray, and its expression was subsequently verified by reverse transcription PCR, real-time PCR, and Western blot analysis, using an EGFRvIII-transfected glioblastoma cell line and glioblastoma tumors as positive controls. Results: Our analysis failed to detect mutations within the tyrosine kinase domain of EGFR in the 11 cell lines and 75 patients tested. The initial analysis of EGFRvIII expression by immunohistochemistry revealed that at least 50% of the patient tumors expressed EGFRvIII in a urothelial carcinoma tissue microarray. Conflicting reports exist, however, regarding the extent of EGFRvIII expression in tissues owing to the specificity of the antibodies and the methodologies used. Therefore, we sought to validate this observation by reverse transcription PCR, real-time PCR, and Western blot analysis. In these assays, none of the samples were positive for EGFRvIII except for control transfectants and glioblastomas. Conclusions: When our results are taken together, we conclude that alterations within the tyrosine kinase domain and expression of EGFRvIII are rare events in bladder cancer. The present study has clinical implications in selecting tyrosine kinase inhibitors for the therapy of urothelial carcinoma.