tbuckley/cabot-search huggingface dataset:
Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes.
Authors: C M Thaik, A Calderone, N Takahashi, W S Colucci
Journal: Journal of Clinical Investigation (1995)

Mononuclear cell infiltration and local cytokine elaboration are hallmarks of inflammatory and immunologic heart diseases. To test the hypothesis that cytokines can modulate cardiac myocyte growth and phenotype, myocytes cultured from neonatal rat hearts were exposed to IL-1 beta, an inflammatory cytokine prevalent in myocardial inflammation. IL-1 beta (2 ng/ml, 24 h) increased [3H]leucine incorporation by 30 +/- 4% (P < 0.001, n = 29) and net cellular protein content by 20 +/- 4% (P < 0.001, n = 27), but had no effect on DNA synthesis. Northern hybridization showed that IL-1 beta increased prepro-atrial natriuretic factor (ANF) mRNA (5.8 +/- 1.5-fold, P < 0.01, n = 13) and beta-myosin heavy chain (beta-MHC) mRNA (> 10-fold, n = 4), and decreased mRNA levels for sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) (-46 +/- 7%; P < 0.001; n = 11), calcium release channel (CRC) (-65 +/- 11%, P < 0.001, n = 8) and voltage-dependent calcium channel (VDCC) (-53 +/- 7%, P < 0.001, n = 8). NG-monomethyl-L-arginine (1 mM), an inhibitor of nitric oxide (NO) synthesis, did not inhibit the IL-1 beta-induced protein synthesis or changes in mRNA levels. In ventricular myocardium obtained from adult rats treated with lipopolysaccharide (4 mg/kg intraperitoneally 18 h) to stimulate systemic cytokine production, there were changes in the mRNA levels for beta-MHC (6 +/- 1-fold, P < 0.01, n = 4), SERCA2 (-65 +/- 4%, P < 0.0001, n = 4), CRC (-67 +/- 5%, P < 0.001, n = 4), and VDCC (-58 +/- 5%, P < 0.001; n = 4) that were qualitatively similar to those observed in cultured myocytes. Thus, IL-1 beta, acting via an NO-independent mechanism, caused myocyte hypertrophy associated with induction of fetal genes (ANF and beta-MHC) and downregulation of three important calcium regulatory genes (SERCA2, CRC, and VDCC). IL-1 beta may contribute to the abnormal structural and functional alterations of cardiac myocytes in conditions marked by mononuclear cell infiltration.
Magnetic Resonance Imaging Captures the Biology of Ductal Carcinoma In Situ
Authors: Laura J. Esserman, Anjali S. Kumar, Alex F. Herrera, Jessica Leung, Alfred Au, Yunn-Yi Chen, Dan H. Moore, Daniel F. Chen, Jennifer Hellawell, Dulcy Wolverton, E. Shelley Hwang, Nola M. Hylton
Journal: Journal of Clinical Oncology (2006)

Purpose Magnetic resonance imaging (MRI) is an important tool for characterizing invasive breast cancer but has proven to be more challenging in the setting of ductal carcinoma in situ (DCIS). We investigated whether MRI features of DCIS reflect differences in biology and pathology. Patients and Methods Forty five of 100 patients with biopsy-proven DCIS who underwent MRI and had sufficient tissue to be characterized by pathologic (nuclear grade, presence of comedo necrosis, size, and density of disease) and immunohistochemical (IHC) findings (proliferation, Ki67; angiogenesis, CD34; and inflammation, CD68). Pathology and MRI features (enhancement patterns, distribution, size, and density) were analyzed using pairwise and canonical correlations. Results Histopathologic and IHC variables correlated with MRI features (r = 0.73). The correlation was largely due to size, density (by either MRI or pathology), and inflammation (P &lt; .05). Most small focal masses were estrogen receptor-positive. MRI enhancement patterns that were clumped were more likely than heterogeneous patterns to be high-grade lesions. Homogenous lesions were large, high grade, and rich in macrophages. Presence of comedo necrosis and size could be distinguished on MRI (P &lt; .05). MRI was most likely to over-represent the size of less dense, diffuse DCIS lesions. Conclusion The heterogeneous presentation of DCIS on MRI reflects underlying histopathologic differences.
Low-Dose Decitabine Versus Best Supportive Care in Elderly Patients With Intermediate- or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group
Authors: Michael Lübbert, Stefan Suciu, Liliana Baila, Björn Hans Rüter, Uwe Platzbecker, Aristoteles Giagounidis, Dominik Selleslag, Boris Labar, Ulrich Germing, Helmut R. Salih, Filip Beeldens, Petra Muus, Karl-Heinz Pflüger, Corneel Coens, Anne Hagemeijer, Hans Eckart Schaefer, Arnold Ganser, Carlo Aul, Theo de Witte, Pierre W. Wijermans
Journal: Journal of Clinical Oncology (2011)

To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy.Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS). Decitabine (15 mg/m(2)) was given intravenously over 4 hours three times a day for 3 days in 6-week cycles.OS prolongation with decitabine versus BSC was not statistically significant (median OS, 10.1 v 8.5 months, respectively; hazard ratio [HR], 0.88; 95% CI, 0.66 to 1.17; two-sided, log-rank P = .38). Progression-free survival (PFS), but not acute myeloid leukemia (AML) -free survival (AMLFS), was significantly prolonged with decitabine versus BSC (median PFS, 6.6 v 3.0 months, respectively; HR, 0.68; 95% CI, 0.52 to 0.88; P = .004; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12; P = .24). AML transformation was significantly (P = .036) reduced at 1 year (from 33% with BSC to 22% with decitabine). Multivariate analyses indicated that patients with short MDS duration had worse outcomes. Best responses with decitabine versus BSC, respectively, were as follows: complete response (13% v 0%), partial response (6% v 0%), hematologic improvement (15% v 2%), stable disease (14% v 22%), progressive disease (29% v 68%), hypoplasia (14% v 0%), and inevaluable (8% v 8%). Grade 3 to 4 febrile neutropenia occurred in 25% of patients on decitabine versus 7% of patients on BSC; grade 3 to 4 infections occurred in 57% and 52% of patients on decitabine and BSC, respectively. Decitabine treatment was associated with improvements in patient-reported quality-of-life (QOL) parameters.Decitabine administered in 6-week cycles is active in older patients with higher-risk MDS, resulting in improvements of OS and AMLFS (nonsignificant), of PFS and AML transformation (significant), and of QOL. Short MDS duration was an independent adverse prognosticator.
A mutation in calsequestrin, CASQ2D307H, impairs Sarcoplasmic Reticulum Ca2+ handling and causes complex ventricular arrhythmias in mice
Authors: W DIRKSEN, V LACOMBE, M CHI, A KALYANASUNDARAM, S VIATCHENKOKARPINSKI, D TERENTYEV, Z ZHOU, S VEDAMOORTHYRAO, N LI, N CHIAMVIMONVAT
Journal: Cardiovascular Research (2007)

Objective A naturally-occurring mutation in cardiac calsequestrin (CASQ2) at amino acid 307 was discovered in a highly inbred family and hypothesized to cause Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The goal of this study was to establish a causal link between CASQ2D307H and the CPVT phenotype using an in vivo model.
Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy
Authors: Gavin M Bendle, Carsten Linnemann, Anna I Hooijkaas, Laura Bies, Moniek A de Witte, Annelies Jorritsma, Andrew D M Kaiser, Nadine Pouw, Reno Debets, Elisa Kieback, Wolfgang Uckert, Ji-Ying Song, John B A G Haanen, Ton N M Schumacher
Journal: Nature Medicine (2010)
Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population
Authors: Henrik Johansson, Katarina Norlander, Lars Berglund, Christer Janson, Andrei Malinovschi, Lennart Nordvall, Leif Nordang, Margareta Emtner
Journal: Thorax (2014)

<h3>Background</h3> Exercise-induced respiratory symptoms are common among adolescents. Exercise is a known stimulus for transient narrowing of the airways, such as exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO). Our aim was to investigate the prevalence of EIB and EILO in a general population of adolescents. <h3>Methods</h3> In this cross-sectional study, a questionnaire on exercise-induced dyspnoea was sent to all adolescents born in 1997 and 1998 in Uppsala, Sweden (n=3838). A random subsample of 146 adolescents (99 with self-reported exercise-induced dyspnoea and 47 without this condition) underwent standardised treadmill exercise tests for EIB and EILO. The exercise test for EIB was performed while breathing dry air; a positive test was defined as a decrease of ≥10% in FEV<sub>1</sub> from baseline. EILO was investigated using continuous laryngoscopy during exercise. <h3>Results</h3> The estimated prevalence of EIB and EILO in the total population was 19.2% and 5.7%, respectively. No gender differences were found. In adolescents with exercise-induced dyspnoea, 39.8% had EIB, 6% had EILO and 4.8% had both conditions. In this group, significantly more boys than girls had neither EIB nor EILO (64.7% vs 38.8%; p=0.026). There were no significant differences in body mass index, lung function, diagnosed asthma or medication between the participants with exercise-induced dyspnoea who had or did not have a positive EIB or EILO test result. <h3>Conclusions</h3> Both EIB and EILO are common causes of exercise-induced dyspnoea in adolescents. EILO is equally common among girls and boys and can coexist with EIB.
Statins Are Associated With a Reduced Incidence of Perioperative Mortality in Patients Undergoing Major Noncardiac Vascular Surgery
Authors: Don Poldermans, Jeroen J. Bax, Miklos D. Kertai, Boudewijn Krenning, Cynthia M. Westerhout, Arend F.L. Schinkel, Ian R. Thomson, Peter J. Lansberg, Lee A. Fleisher, Jan Klein, Hero van Urk, Jos R.T.C. Roelandt, Eric Boersma
Journal: Circulation (2003)

Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall.To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%; P<0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors.This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.
Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Authors: Hagop M. Kantarjian, Xavier G. Thomas, Anna Dmoszynska, Agnieszka Wierzbowska, Grzegorz Mazur, Jiri Mayer, Jyh-Pyng Gau, Wen-Chien Chou, Rena Buckstein, Jaroslav Cermak, Ching-Yuan Kuo, Albert Oriol, Farhad Ravandi, Stefan Faderl, Jacques Delaunay, Daniel Lysák, Mark Minden, Christopher Arthur
Journal: Journal of Clinical Oncology (2012)

This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics.Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m(2) per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m(2) per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded.The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%).In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis.
Chronic phencyclidine abuse and physical assault
Authors: A M Khajawall, T B Erickson, G M Simpson
Journal: American Journal of Psychiatry (1982)

When the authors investigated aggressive behavior on a phencyclidine (PCP) detoxification and rehabilitation unit and compared similar types of behavior on a heroin unit, they found no differences between the two units. The urinary PCP levels of a subgroup of 75 patients admitted to the PCP unit who had PCP-positive urine were significantly higher than those of 75 patients admitted to an acute psychiatric ward because of violent behavior who also had PCP-positive urine. The authors discuss the implications of these findings and the need for more information on the relationship between PCP levels in blood and urine and behavior.
A Codon-Based Model of Host-Specific Selection in Parasites, with an Application to the Influenza A Virus
Authors: R. Forsberg
Journal: Molecular Biology and Evolution (2003)

Parasites sometimes expand their host range by acquiring a new host species. After a host change event, the selective regime acting on a given parasite gene may change as a result of host-specific adaptive alterations of protein functionality or host-specific immune-mediated selection. We present a codon-based model that attempts to include these effects by allowing the position-specific substitution process to change in conjunction with a host change event. Following maximum-likelihood parameter estimation, we employ an empirical Bayesian procedure to identify candidate sites potentially involved in host-specific adaptation. We discuss the applicability of the model to the more general problem of ascertaining whether the selective regime differs in two groups of related organisms. The utility of the model is illustrated on a data set of nucleoprotein sequences from the influenza A virus obtained from avian and human hosts.
Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI
Authors: Lukas Martin Wildi, Jean-Pierre Raynauld, Johanne Martel-Pelletier, André Beaulieu, Louis Bessette, Frédéric Morin, François Abram, Marc Dorais, Jean-Pierre Pelletier
Journal: Annals of the Rheumatic Diseases (2011)

Objective To determine the effect of chondroitin sulphate (CS) treatment on cartilage volume loss, subchondral bone marrow lesions (BML), synovitis and disease symptoms in patients with knee osteoarthritis (OA). Methods In this pilot multicentre, randomised, double-blind, controlled trial in primary knee OA, 69 patients with clinical signs of synovitis were randomised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily. Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months; synovial membrane thickness was assessed at baseline and at 6 months. Results The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee (p=0.030), lateral compartment (p=0.015) and tibial plateaus (p=0.002), with significance persisting at 12 months. Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment (p=0.035) and the lateral femoral condyle (p=0.044). Disease symptoms were similar between the two groups. Conclusion CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment, and BML at 12 months. These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA.
Breast Cancer Index predicts pathological complete response and eligibility for breast conserving surgery in breast cancer patients treated with neoadjuvant chemotherapy
Authors: M.C. Mathieu, C. Mazouni, N.C. Kesty, Y. Zhang, V. Scott, J. Passeron, M. Arnedos, C.A. Schnabel, S. Delaloge, M.G. Erlander, F. André
Journal: Annals of Oncology (2011)
Response to Open Peer Commentaries on “Three Ways to Politicize Bioethics”
Authors: Mark B. Brown
Journal: The American Journal of Bioethics (2009)

My primary aim in writing this article was to promote more thoughtful discussion of what it means and could mean to politicize bioethics. The peer commentaries are encouraging in this regard, and I am grateful to the authors for taking the time to respond. I am not sure how Sam Berger (2009) got the idea that republicanism involves “the elimination of interest groups” or that it might “hide groups’ actions behind the veneer of individual citizen engagement” (61). Berger’s characterization might apply to an extreme version of communitarian republicanism, which my article explicitly rejects. The Machiavellian republicanism I describe relies on diverse institutions and associations — including interest groups, although I focus on bioethics councils — for facilitating popular political engagement. Moreover, I endorse the “liberal emphasis on the irreducible plurality of values and interests in modern societies,” (Brown 2009, 43) and I note that excluding interests from public deliberation works against disadvantaged groups. The article also includes a paragraph on “non-deliberative contributions to public bioethics” where I praise the actions of a disability rights group (43). It is true that some theorists of republicanism and deliberative democracy have neglected interest groups, but my article criticizes the standard liberal view of politics for “reducing it to interest group competition,” (43, emphasis added) not interest group competition as such. Berger’s (2009) other main point is that my article “ignores political realities” (61) by underestimating the difficulties of promoting intelligent public engagement in complex bioethical issues. Here Berger’s comment overlaps with Chris Durante’s concern that my article “lacks a detailed method of engaging the public” (55). My article did not aim to provide such a method, nor to describe the practical challenges of public engagement. Berger (2009) notes correctly that popular understanding of many bioethical issues is rather dismal, and that public opinion is necessarily framed and easily manipulated by the media. But criticizing efforts to expand public engagement on the basis of poor public understanding of science puts the cart before the horse. Is it really surprising that standard public surveys regarding isolated scientific facts reveal widespread ignorance? Who
Noninvasive assessment of cardiomyopathy development with simultaneous measurement of topical 1H- and 31P-magnetic resonance spectroscopy.
Authors: T Toyo-oka, K Nagayama, J Suzuki, T Sugimoto
Journal: Circulation (1992)

Background. It might be possible to estimate the metabolic derangement of cardiac muscle by topical nuclear magnetic resonance spectroscopy (MRS) in vivo without killing the animal. Methods and Results. By use of topical 1H- and 31P-MRS focused on the heart of Syrian hamsters with or without cardiomyopathy (CM; BIO 14.6 strain), the chemical constituents were measured in vivo nondestructively and repetitively at several stages of development of CM. A phantom experiment and two-dimensional plot of chain methylenes (CH2) of lipid/water ratio by 1H-MRS versus creatine phosphate (CP)/[beta-P]ATP ratio by 31P-MRS indicated that signal cross talk from the adjacent organs was negligible. Even before the onset of clinical or pathological manifestation of CM (7 weeks after birth), CH2/water ratio by 1H-MRS was lower in the CM group (7.3 +/- 0.7%) than in control (11.8 +/- 2.0%, p less than 0.05), and it decreased further at the hypertrophic stage (17 weeks, 4.1 +/- 0.7%, p less than 0.05) and the congestive stage (27 weeks, 4.3 +/- 0.9%, p less than 0.05). In contrast, the CP/[beta-P]ATP ratio by 31P-MRS started to decrease at the hypertrophic stage (1.90 +/- 0.18 versus 2.52 +/- 0.24, p less than 0.05) and decreased further at the congestive stage to 1.53 +/- 0.18 (p less than 0.01). These in vivo MRS data were confirmed by both biochemical assay and in vitro MRS analysis in heavy water after the animals were killed. Conclusions. A combination of topical 1H-MRS and 31P-MRS in vivo is promising for the noninvasive and sensitive assessment of cardiac muscle metabolism. Comparison of these MRS studies and biochemical analysis suggested not only the modification of water, lipid, CP, or ATP contents but also the reduction of flexibility or fluidity of lipids in cardiomyopathic heart.