tbuckley/cabot-search huggingface dataset:
Role of Radiotherapy to Bulky Disease in Elderly Patients With Aggressive B-Cell Lymphoma
Authors: Gerhard Held, Niels Murawski, Marita Ziepert, Jochen Fleckenstein, Viola Pöschel, Carsten Zwick, Jörg Bittenbring, Mathias Hänel, Sibylla Wilhelm, Jörg Schubert, Norbert Schmitz, Markus Löffler, Christian Rübe, Michael Pfreundschuh
Journal: Journal of Clinical Oncology (2014)

R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is standard care for aggressive B-cell lymphoma. A prospective trial was conducted to investigate the role of additive radiotherapy (RT) to bulky and extralymphatic disease.The best arm of the RICOVER-60 trial (6×R-CHOP-14+2R [R-CHOP administered once every 2 weeks plus two additional applications of rituximab] plus involved-field RT [36 Gy] to sites of initial bulky [≥ 7.5 cm] disease and extralymphatic involvement) was compared with a cohort receiving the same immunochemotherapy but without RT in an amendment to the RICOVER-60 trial (RICOVER-noRTh) in a prospective fashion.After a median observation time of 39 months, 164 of 166 RICOVER-noRTh patients were evaluable. In a multivariable analysis of the intention-to-treat population adjusting for International Prognostic Index risk factors and age (> 70 years), event-free survival (EFS) of patients with bulky disease was inferior without additive RT (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.5; P = .005), with trends for inferior progression-free (PFS; HR, 1.8; 95% CI, 1.0 to 3.3; P = .058) and overall survival (OS; HR, 1.6; 95% CI, 0.9 to 3.1; P = .127). In a per-protocol analysis with 11 patients in RICOVER-noRTh excluded for receiving unplanned RT, multivariable analysis revealed HRs of 2.7 (95% CI, 1.3 to 5.9; P = .011) for EFS, 4.4 (95% CI, 1.8 to 10.6; P = .001) for PFS, and 4.3 (95% CI, 1.7 to 11.1; P = .002) for OS for patients not receiving RT to bulky disease.Additive RT to bulky sites abrogates bulky disease as a risk factor and improves outcome of elderly patients with aggressive B-cell lymphoma. Whether RT can be spared in patients with (metabolic) complete remission after immunochemotherapy must be addressed in appropriately designed prospective trials.
Role of the Cholinergic Antiinflammatory Pathway in Murine Autoimmune Myocarditis
Authors: Christoph Leib, Stefan Göser, Dorit Lüthje, Renate Öttl, Theresa Tretter, Felix Lasitschka, Stefan Zittrich, Gabriele Pfitzer, Hugo A. Katus, Ziya Kaya
Journal: Circulation Research (2011)

Rationale: This study was performed to gain insights into novel therapeutic approaches for the treatment of autoimmune myocarditis. Objective: Chemical stimulation of the efferent arm of the vagus nerve through activation of nicotinic acetylcholine receptor subtype-7α (α7-nAChR) has been shown to be protective in several models of inflammatory diseases. In the present study, we investigated the potentially protective effect of vagus nerve stimulation on myocarditis. Methods and Results: A/J mice were immunized with cardiac troponin I (TnI) to induce autoimmune myocarditis. Mice were exposed to drinking water that contained nicotine in different concentrations and for different time periods (for 3 days at 12.5 mg/L; 3 days at 125 mg/L; 21 days at 12.5 mg/L; and 21 days at 125 mg/L after first immunization). TnI-immunized mice with no pharmacological treatment showed extensive myocardial inflammation and fibrosis and significantly elevated levels of interleukin-6 and tumor necrosis factor-α. Furthermore, elevated levels of mRNA transcripts of proinflammatory chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and RANTES) and chemokine receptors (CCR1, CCR2, and CCR5) were found. Oral nicotine administration reduced inflammation within the myocardium, decreased the production of interleukin-6 and tumor necrosis factor-α, and downregulated the expression of monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, RANTES, CCR1, CCR2, and CCR5. In addition, nicotine treatment resulted in decreased expression of matrix metalloproteinase-14, natriuretic peptide precursor B, tissue inhibitor of metalloproteinase-1, and osteopontin, proteins that are commonly involved in heart failure. Finally, we found that nicotine reduced levels of pSTAT3 (phosphorylated signal transducer and activator of transcription 3) protein expression within the myocardium. Neostigmine treatment did not affect the progression of myocarditis. Conclusions: We showed that activation of the cholinergic antiinflammatory pathway with nicotine reduces inflammation in autoimmune myocarditis. Our results may open new possibilities in the therapeutic management of autoimmune myocarditis.
Respiratory Complications from Tetraethylammonium Ion
Authors: GEORGE A. MCLEMORE, HAROLD D. GREEN, THOMAS N. LIDE
Journal: Circulation (1951)

Ill effects of tetraethylammonium ion reported in the current literature are reviewed. Two deaths are reported which are considered to be attributable to this substance; one resulted from a myocardial infarction, the other was due to respiratory failure. Four dogs were given progressively increasing doses of tetraethylammonium ion and all ultimately died of respiratory failure.
TLX1-Induced T-cell Acute Lymphoblastic Leukemia
Authors: Kim De Keersmaecker, Adolfo A. Ferrando
Journal: Clinical Cancer Research (2011)

The TLX1 transcription factor oncogene is frequently activated by chromosomal translocations in T-cell acute lymphoblastic leukemia (T-ALL) and defines a distinct molecular group of tumors characterized by differentiation arrest at the early cortical stage of thymocyte differentiation and excellent response to therapy. Recent developments from the analysis of genomic data on TLX1-specific transcriptional targets and analysis of the molecular mechanisms of TLX1 transformation in human- and mouse-induced leukemias have shown novel insight into the activity of this transcription factor oncogene. Aberrant expression of TLX1 in T-cell progenitors disrupts normal T-cell development and triggers the development of aneuploidy during T-cell transformation. Importantly, the disruption of the mitotic checkpoint in TLX1-induced tumors may be linked not only to the acquisition of secondary genetic alterations in T-ALL but also to increased sensitivity of these tumors to chemotherapy with drugs targeting the formation of the mitotic spindle.
Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies
Authors: A.L. Wong, R.A. Soo, D.S. Tan, S.C. Lee, J.S. Lim, P.C. Marban, L.R. Kong, Y.J. Lee, L.Z. Wang, W.L. Thuya, R. Soong, M.Q. Yee, T.M. Chin, M.T. Cordero, B.R. Asuncion, B. Pang, S. Pervaiz, J.L. Hirpara, A. Sinha, W.W. Xu, M. Yuasa, T. Tsunoda, M. Motoyama, T. Yamauchi, B.C. Goh
Journal: Annals of Oncology (2015)
Environmental Tobacco Smoke and Lung Cancer in Nonsmoking Women-Reply
Authors: Elizabeth T.H. Fontham, Pelayo Correa, Vivien W. Chen, Peggy Reynolds, Ann Williams, Patricia A. Buffler, Toni Alterman, Raymond S. Greenberg, Jonathan Liff, Peggy Boyd, Donald F. Austin
Journal: JAMA (1995)

<h3>In Reply.</h3> —We concur with Dr Kirkland that subgroups of exposure are of less interest than total exposure to ETS and, as noted in our report, some exposures are more likely to be accurately recalled and reported than others. However, to estimate the risk of exposure to ETS, it is necessary to ask specific questions about exposures in a variety of settings during different time periods and then to summarize those data as we did in Table 5 for all childhood exposures combined and in Tables 7 and 8 for all adulthood exposures combined. The study was designed to collect data on a finite number of subgroups and to combine the subgroup data to categorize study subjects into levels of exposure ranging from little or none to lengthy. The unit of exposure was "years," which does not presume a level of precision that is unachievable (eg, hours per day per
Interleukin 2 Treatment for HIV Infection
Authors: Joel Blankson
Journal: JAMA (2000)

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Interferon-γ ELISPOT as a Biomarker of Treatment Efficacy in Latent Tuberculosis Infection
Authors: Ifedayo M. Adetifa, Martin O. C. Ota, David J. Jeffries, Moses D. Lugos, Abdulrahman S. Hammond, Nicholas J. Battersby, Patrick K. Owiafe, Simon D. Donkor, Martin Antonio, Hannah B. Ibanga, Roger H. Brookes, Peter Aka, Robert Walton, Richard A. Adegbola, Philip C. Hill
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required.Objectives: To evaluate ESAT-6 and CFP-10 (EC) IFN-γ ELISPOT as a biomarker for treatment efficacy in LTBI.Methods: This was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants.Measurements and Main Results: Participants received a 6-month course of 900 mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tested for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6 between treatment arms was compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model was fitted to allow for zero inflation and overdispersion of quantitative response. The proportions of EC ELISPOT–positive subjects reduced over time (P < 0.001) but did not differ by study arm (P = 0.36). Median spot-forming units for ESAT-6 and CFP-10 also declined significantly with time (P < 0.001) but did not differ by study arm (P = 0.74 and 0.71, respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time.Conclusions: In contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen–specific T-cell responses over time. IFN-γ ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI.Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).
Genetic Deletion of Myostatin From the Heart Prevents Skeletal Muscle Atrophy in Heart Failure
Authors: Joerg Heineke, Mannix Auger-Messier, Jian Xu, Michelle Sargent, Allen York, Stephen Welle, Jeffery D. Molkentin
Journal: Circulation (2010)

Background— Cardiac cachexia is characterized by an exaggerated loss of skeletal muscle, weakness, and exercise intolerance, although the cause of these effects remains unknown. Here, we hypothesized that the heart functions as an endocrine organ in promoting systemic cachexia by secreting peptide factors such as myostatin. Myostatin is a cytokine of the transforming growth factor-β superfamily that is known to control muscle wasting. Methods and Results— We used a Cre/loxP system to ablate myostatin ( Mstn gene) expression in a cell type-specific manner. As expected, elimination of Mstn selectively in skeletal muscle with a myosin light chain 1f ( MLC1f )- cre allele induced robust hypertrophy in all skeletal muscle. However, heart-specific deletion of Mstn with an Nkx2.5-cre allele did not alter baseline heart size or secondarily affect skeletal muscle size, but the characteristic wasting and atrophy of skeletal muscle that typify heart failure were not observed in these heart-specific null mice, indicating that myocardial myostatin expression controls muscle atrophy in heart failure. Indeed, myostatin levels in the plasma were significantly increased in wild-type mice subjected to pressure overload-induced cardiac hypertrophy but not in Mstn heart-specific deleted mice. Moreover, cardiac-specific overexpression of myostatin, which increased circulating levels of myostatin by 3- to 4-fold, caused a reduction in weight of the quadriceps, gastrocnemius, soleus, and even the heart itself. Finally, to investigate myostatin as a potential therapeutic target for the treatment of muscle wasting in heart failure, we infused a myostatin blocking antibody (JA-16), which promoted greater maintenance of muscle mass in heart failure. Conclusions— Myostatin released from cardiomyocytes induces skeletal muscle wasting in heart failure. Targeted inhibition of myostatin in cardiac cachexia might be a therapeutic option in the future.
Characteristics of left ventricular receptors with nonmedullated vagal afferents in cats.
Authors: P N Thorén
Journal: Circulation Research (1977)

Activity from left ventricular receptors with non-medullated afferents was recorded in the right cervical vagus in anesthetized, thoracotomized cats. Probing of the open heart demonstrated that the receptors were distributed throughout the free wall and the interventricular septum. Fibers from posterior receptors pass along the posterior descending coronary artery and the lateral surface of the right atrium to join the right main cardiac nerve; those from the anteriolateral region pass behind the aorta and the pulmonary trunk. The control receptor discharge was 1.4 (range, 0-6) impulses/sec at a mean left ventricular end-diastolic pressure (LVEDP) of 4.5 (range, 2-10) mm Hg. It was observed that receptor discharge increased with progressive increase in LVEDP produced either by transfusion or by aortic occlusion. At a mean LVEDP of 8 mm Hg, the mean discharge rate was 3.2 impulses/sec, and at 16 mm Hg it was 7.0 impulses/sec. It was also found that propranolol reduced and isoproterenol increased the discharge frequency at any given LVEDP. Measurement of total conduction times indicated that during the increase in LVEDP the receptors were activated principally in the systolic portion of the cardiac cycle. Despite this there was no obvious relationship between the discharge frequency and left ventricular systolic pressure.
Choline Kinase Down-regulation Increases the Effect of 5-Fluorouracil in Breast Cancer Cells
Authors: Noriko Mori, Kristine Glunde, Tomoyo Takagi, Venu Raman, Zaver M. Bhujwalla
Journal: Cancer Research (2007)

Identifying strategies to increase cancer cell kill while sparing normal tissue is critically important in cancer chemotherapy. Choline kinase (Chk), the enzyme that converts choline to phosphocholine (PC), is elevated in cancer cells and presents a novel target for increasing cell kill. Here, we have examined the effects of transiently down-regulating Chk by small interfering RNA against Chk (siRNA-chk) on PC and total choline-containing compound (tCho) levels and on the viability/proliferation of estrogen receptor-negative and estrogen receptor-positive breast cancer cell lines and a nonmalignant mammary epithelial cell line. We investigated the effects of combination treatment with transient siRNA-chk transfection and the anticancer drug 5-fluorouracil (5-FU) in those cell lines. Microarray analysis of the invasive estrogen receptor-negative MDA-MB-231 cell line was done to characterize molecular changes associated with Chk down-regulation. Chk down-regulation decreased PC and tCho levels in the malignant cell lines, whereas the cell viability/proliferation assays detected a decrease in proliferation in these cells. In contrast, Chk down-regulation had an almost negligible effect on PC and tCho levels as well as cell viability/proliferation in the nonmalignant cell line. A combination of siRNA-chk with 5-FU treatment resulted in a larger reduction of cell viability/proliferation in the breast cancer cell lines; this reduction was evident to a much lesser degree in the nonmalignant cells. Microarray analysis showed that Chk down-regulation affected 33 proliferation-related genes and 9 DNA repair-related genes. Chk down-regulation with siRNA-chk may provide a novel alternative to enhance the effect of anticancer drugs in malignant cells.
A Genome-Wide Scan for Linkage to Chromosomal Regions in 382 Sibling Pairs With Schizophrenia or Schizoaffective Disorder
Authors: Lynn E. DeLisi, Sarah H. Shaw, Timothy J. Crow, Gail Shields, Angela B. Smith, Veronica W. Larach, Nigel Wellman, Josephine Loftus, Betsy Nanthakumar, Kamran Razi, John Stewart, Margherita Comazzi, Antonio Vita, Thomas Heffner, Robin Sherrington
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Some genome-wide scans and association studies for schizophrenia susceptibility genes have yielded significant positive findings, but there is disagreement between studies on their locations, and no mutation has yet been found in any gene. Since schizophrenia is a complex disorder, a study with sufficient power to detect a locus with a small or moderate gene effect is necessary. METHOD: In a genome-wide scan of 382 sibling pairs with a diagnosis of schizophrenia or schizoaffective disorder, 396 highly polymorphic markers spaced approximately 10 centimorgans apart throughout the genome were genotyped in all individuals. Multipoint nonparametric linkage analysis was performed to evaluate regions of the genome demonstrating increased allele sharing, as measured by a lod score. RESULTS: Two regions with multipoint maximum lod scores suggesting linkage were found. The highest lod scores occurred on chromosome 10p15-p13 (peak lod score of 3.60 at marker D10S189) and the centromeric region of chromosome 2 (peak lod score of 2.99 at marker D2S139). In addition, a maximum lod score of 2.00 was observed with marker D22S283 on chromosome 22q12, which showed evidence of an imprinting effect, whereby an excess sharing of maternal, but not paternal, alleles was present. No evidence of linkage was obtained at several locations identified in previous studies, including chromosomes 1q, 4p, 5p-q, 6p, 8p, 13q, 15p, and 18p. CONCLUSIONS: The findings of this large genome-wide scan emphasize the weakness and fragility of linkage reports on schizophrenia. No linkage appears to be consistently replicable across large studies. Thus, it has to be questioned whether the genetic contribution to this disorder is detectable by these strategies and the possibility raised that it may be epigenetic, i.e., related to gene expression rather than sequence variation. Nevertheless, the positive findings on chromosome 2, 10, and 22 should be pursued further.
Serum levels of collagen type‐I degradation markers are associated with vascular stiffness in chronic heart failure patients
Authors: Sofia V. Chatzikyriakou, Dimitrios N. Tziakas, Georgios K. Chalikias, Dimitrios A. Stakos, Adina K. Thomaidi, Konstantina Mitrousi, Asimina E. Lantzouraki, Stamatia Kotsiou, Efstratios Maltezos, Harisios Boudoulas
Journal: European Journal of Heart Failure (2008)
B-Scan Ultrasonography to Screen for Retinal Tears in Acute Symptomatic Age-Related Posterior Vitreous Detachment
Authors: Jose Lorenzo-Carrero, Ines Perez-Flores, Monica Cid-Galano, Marta Fernandez-Fernandez, Fernando Heras-Raposo, Ramon Vazquez-Nuñez, Marta Lopez-Fuentes
Journal: Ophthalmology (2008)
EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis
Authors: Yvonne van Eijk-Hustings, Astrid van Tubergen, Carina Boström, Elena Braychenko, Beate Buss, José Felix, Jill Firth, Alison Hammond, Benny Harston, Cristina Hernandez, Masa Huzjak, Jana Korandová, Marja Leena Kukkurainen, Robert Landewé, Maryse Mezieres, Marijana Milincovic, Antonella Moretti, Susan Oliver, Jette Primdahl, Marieke Scholte-Voshaar, Jenny de la Torre-Aboki, Jennifer Waite-Jones, Rene Westhovens, Heidi Andersen Zangi, Turid Heiberg, Jackie Hill
Journal: Annals of the Rheumatic Diseases (2011)

Objectives The authors aim to develop European League Against Rheumatism recommendations for the role of the nurse in the management of patients with chronic inflammatory arthritis, to identify a research agenda and to determine an educational agenda. Methods A task force made up of a multidisciplinary expert panel including nurses, rheumatologists, occupational therapist, physiotherapist, psychologist, epidemiologist and patient representatives, representing 14 European countries, carried out the development of the recommendations, following the European League Against Rheumatism standardised operating procedures. The task force met twice. In the first meeting, the aims of the task force were defined, and eight research questions were developed. This was followed by a comprehensive, systematic literature search. In the second meeting, the results from the literature review were presented to the task force that subsequently formulated the recommendations, research agenda and educational agenda. Results In total, 10 recommendations were formulated. Seven recommendations covered the contribution of nurses to care and management: education, satisfaction with care, access to care, disease management, psychosocial support, self-management and efficiency of care. Three recommendations focused on professional support for nurses: availability of guidelines or protocols, access to education and encouragement to undertake extended roles. The strength of the recommendations varied from A to C, dependent on the category of evidence (1A–3), and a high level of agreement was achieved. Additionally, the task force agreed upon 10 topics for future research and an educational agenda. Conclusion 10 recommendations for the role of the nurse in the management of chronic inflammatory arthritis were developed using a combination of evidence-based and expert consensus approach.
Three-Dimensional Impulse Propagation in Myocardium
Authors: Bruce H. Smaill, Jichao Zhao, Mark L. Trew
Journal: Circulation Research (2013)

Impulse propagation in the heart depends on the excitability of individual cardiomyocytes, impulse transmission between adjacent myocytes, and the 3-dimensional arrangement of those cells. Here, we review the role of each of these factors in normal and aberrant cardiac electric activation, with particular emphasis on the effects of 3-dimensional myocyte architecture at the tissue scale. The analysis draws on findings from in vivo and in vitro experiments, as well as biophysically based computer models that have been used to integrate and interpret these experimental data. It indicates that discontinuous arrangement of myocytes and extracellular connective tissue at the tissue scale can give rise to current source-to-sink mismatch, spatiotemporal distribution of refractoriness, and rate-sensitive electric instability, which contribute to the initiation and maintenance of reentrant cardiac arrhythmia. This exacerbates the risk of rhythm disturbance associated with heart disease. We conclude that structure-based, multiscale computer models that incorporate accurate information about local cellular electric activity provide a powerful platform for investigating the basis of reentrant cardiac arrhythmia. However, it is important that these models capture key features of structure and related electric function at the tissue scale.