tbuckley/cabot-search huggingface dataset:
Pulmonary-Vein Isolation for Atrial Fibrillation in Patients with Heart Failure
Authors: Mohammed N. Khan, Pierre Jaïs, Jennifer Cummings, Luigi Di Biase, Prashanthan Sanders, David O. Martin, Josef Kautzner, Steven Hao, Sakis Themistoclakis, Raffaele Fanelli, Domenico Potenza, Raimondo Massaro, Oussama Wazni, Robert Schweikert, Walid Saliba, Paul Wang, Amin Al-Ahmad, Salwa Beheiry, Pietro Santarelli, Randall C. Starling, Antonio Dello Russo, Gemma Pelargonio, Johannes Brachmann, Volker Schibgilla, Aldo Bonso, Michela Casella, Antonio Raviele, Michel Haïssaguerre, Andrea Natale
Journal: New England Journal of Medicine (2008)

Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure.In this prospective, multicenter clinical trial, we randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40% or less, and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing. All patients completed the Minnesota Living with Heart Failure questionnaire (scores range from 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-minute walk test (the composite primary end point). Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation.In all, 41 patients underwent pulmonary-vein isolation, and 40 underwent atrioventricular-node ablation with biventricular pacing; none were lost to follow-up at 6 months. The composite primary end point favored the group that underwent pulmonary-vein isolation, with an improved questionnaire score at 6 months (60, vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing; P<0.001), a longer 6-minute-walk distance (340 m vs. 297 m, P<0.001), and a higher ejection fraction (35% vs. 28%, P<0.001). In the group that underwent pulmonary-vein isolation, 88% of patients receiving antiarrhythmic drugs and 71% of those not receiving such drugs were free of atrial fibrillation at 6 months. In the group that underwent pulmonary-vein isolation, pulmonary-vein stenosis developed in two patients, pericardial effusion in one, and pulmonary edema in another; in the group that underwent atrioventricular-node ablation with biventricular pacing, lead dislodgment was found in one patient and pneumothorax in another.Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation. (ClinicalTrials.gov number, NCT00599976.)
Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.
Authors: R D Cohen, L W Castellani, J H Qiao, B J Van Lenten, A J Lusis, K Reue
Journal: Journal of Clinical Investigation (1997)

Transgenic mouse lines carrying several copies of the mouse apo A-IV gene were produced. Lipoprotein composition and function, and aortic lesion development were examined. Apo A-IV levels in the plasma of transgenic mice were elevated threefold compared with nontransgenic littermates on a chow diet, and sixfold in mice fed an atherogenic diet. Plasma concentrations of total cholesterol, HDL cholesterol, triglycerides, and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0.05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and free fatty acids (P < 0.05), and lower levels of unesterified cholesterol (P < 0.05), than nontransgenic littermates. Expression of the apo A-IV transgene had a protective effect against the formation of diet-induced aortic lesions, with transgenics exhibiting lesion scores of approximately 30% those seen in control mice. HDL-sized lipoproteins isolated from transgenic mice fed the atherogenic diet promoted cholesterol efflux from cholesterol-loaded human monocytes more efficiently than comparable lipoproteins from nontransgenic counterparts. Plasma from transgenics also exhibited higher endogenous cholesterol esterification rates. Taken together, these results suggest that apo A-IV levels influence the metabolism and antiatherogenic properties of HDL.
Increased Arterial Blood Pressure and Vascular Remodeling in Mice Lacking Salt-Inducible Kinase 1 (SIK1)
Authors: Alejandro M. Bertorello, Nuno Pires, Bruno Igreja, Maria João Pinho, Emina Vorkapic, Dick Wågsäter, Johannes Wikström, Margareta Behrendt, Anders Hamsten, Per Eriksson, Patricio Soares-da-Silva, Laura Brion
Journal: Circulation Research (2015)

In human genetic studies a single nucleotide polymorphism within the salt-inducible kinase 1 (SIK1) gene was associated with hypertension. Lower SIK1 activity in vascular smooth muscle cells (VSMCs) leads to decreased sodium-potassium ATPase activity, which associates with increased vascular tone. Also, SIK1 participates in a negative feedback mechanism on the transforming growth factor-β1 signaling and downregulation of SIK1 induces the expression of extracellular matrix remodeling genes.To evaluate whether reduced expression/activity of SIK1 alone or in combination with elevated salt intake could modify the structure and function of the vasculature, leading to higher blood pressure.SIK1 knockout (sik1(-/-)) and wild-type (sik1(+/+)) mice were challenged to a normal- or chronic high-salt intake (1% NaCl). Under normal-salt conditions, the sik1(-/-) mice showed increased collagen deposition in the aorta but similar blood pressure compared with the sik1(+/+) mice. During high-salt intake, the sik1(+/+) mice exhibited an increase in SIK1 expression in the VSMCs layer of the aorta, whereas the sik1(-/-) mice exhibited upregulated transforming growth factor-β1 signaling and increased expression of endothelin-1 and genes involved in VSMC contraction, higher systolic blood pressure, and signs of cardiac hypertrophy. In vitro knockdown of SIK1 induced upregulation of collagen in aortic adventitial fibroblasts and enhanced the expression of contractile markers and of endothelin-1 in VSMCs.Vascular SIK1 activation might represent a novel mechanism involved in the prevention of high blood pressure development triggered by high-salt intake through the modulation of the contractile phenotype of VSMCs via transforming growth factor-β1-signaling inhibition.
T cell memory. Long-term persistence of virus-specific cytotoxic T cells.
Authors: B D Jamieson, R Ahmed
Journal: The Journal of Experimental Medicine (1989)

This study documents that virus-specific CTL can persist indefinitely in vivo. This was accomplished by transferring Thy-1.1 T cells into Thy-1.2 recipient mice to specifically identify the donor T cell population and to characterize its antigenic specificity and function by using a virus-specific CTL assay. Thy-1.1+ T cells from mice previously immunized with lymphocytic choriomeningitis virus (LCMV) were transferred into Thy-1.2 mice persistently infected with LCMV. The transferred LCMV-specific CTL (Thy-1.1+ CD8+) eliminate virus from the chronically infected carriers and persist in the recipient mice in small numbers, comprising only a minor fraction of the total T cells. Upon re-exposure to virus, these long-lived "resting" CD8+ T cells proliferate in vivo to become the predominant cell population. These donor CD8+ T cells can be recovered up to a year post-transfer and still retain antigenic specificity and biological function. They kill LCMV infected H-2-matched cells in vitro and can eliminate virus upon transfer into a second infected host. In addition, these long-lived CD8+ T cells appear not to be dependent on help from CD4+ T cells, since depletion of CD4+ T cells has minimal or no effect on their biological properties (proliferation, CTL response, viral clearance). These donor CTL also exhibit an immunodominance over the host-derived LCMV-specific CTL response. When both host and donor T cells are present, the donor CTL response is dominant over the potential CTL response of the cured carrier host. Taken together, these results suggest that virus-specific CTL can persist for the life span of the host as memory cells.
Systemic Medications and Glaucoma Patients⁎ ⁎Presented at: American Glaucoma Society meeting, March, 2005; Snowbird, Utah. Study sponsored by Alcon Laboratories, Inc., Fort Worth, Texas. Drs Robin and Novack are consultants to and Mr Covert is an employee of and stockholder in Alcon Laboratories, Inc. Dr Robin is also a consultant to Pfizer and Merck.
Authors: David Covert, Alan L. Robin, Gary D. Novack
Journal: Ophthalmology (2005)
Amino acid excretion in primary hyperuricaemia.
Authors: D Kaplan, H Diamond, S L Wallace, D Halberstam
Journal: Annals of the Rheumatic Diseases (1969)

Material and Methods 51 men between the ages of 21 and 67 years were studied; 26 were normouricaemic, and 25 had primary hyperuricaemia (serum uric acid greater than 7 mg.per cent.), of whom all but two had a history ofgouty arthritis, though none were tophaceous.None of the subjects was acutely ill at the time of the study.None had taken
Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial
Authors: J Donald Easton, Renato D Lopes, M Cecilia Bahit, Daniel M Wojdyla, Christopher B Granger, Lars Wallentin, Marco Alings, Shinya Goto, Basil S Lewis, Mårten Rosenqvist, Michael Hanna, Puneet Mohan, John H Alexander, Hans-Christoph Diener
Journal: The Lancet Neurology (2012)
Immunohistochemical delineation of the conduction system. II: The atrioventricular node and Purkinje fibers.
Authors: P W Oosthoek, S Virágh, W H Lamers, A F Moorman
Journal: Circulation Research (1993)

Using an antibody that reacts specifically with the myocytes of the conduction system of the bovine heart, we have studied the atrioventricular node and the spatial distribution of the Purkinje fibers in the bovine heart. This study was complemented by studying the distribution of the gap junction protein connexin43 in these areas in the bovine heart and in the human heart. The large Purkinje fibers in the bovine heart are arranged in a two-dimensional network underneath the endocardium. At discrete sites, these fibers branch to the Purkinje fibers situated between the muscle bundles of the ventricular mass. These intramural Purkinje fibers are arranged in sheets that form a complex three-dimensional network of lamellas. Contacts with the ventricular myocytes are found throughout the myocardial wall, with the exception of a subepicardial layer of 2-mm thickness, ie, 10% to 15% of the wall thickness. The spatial arrangement of the Purkinje fibers correlates well with data on electrophysiology. Connexin43 was not detected in the myocytes of the atrioventricular node, whereas in the Purkinje fibers of the atrioventricular bundle and of the bundle branches, abundant expression of connexin43 was found in both humans and cows. In the bovine Purkinje fibers, a remarkable subcellular distribution of connexin43 is found: it occupies the entire plasma membrane facing other Purkinje cells but not that facing the surrounding connective tissue. The structural differences in architecture of the ventricular conduction system in humans and cows seems not to result in substantial differences in conduction velocities. However, the Purkinje fiber network in the bovine heart may explain the efficient ventricular excitation, as reflected by the relatively short QRS complex compared with that in the human heart, where intramural Purkinje fibers are not found.
16 ANALYSIS OF HBsAg LEVELS IN PATIENTS COINFECTED WITH HEPATITIS B VIRUS AND HEPATITIS C VIRUS TREATED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN
Authors: C.-J. Liu, W.-L. Chuang, C.-M. Lee, M.-L. Yu, S.-N. Lu, S.-S. Wu, L.-Y. Liao, C.-L. Chen, H.-T. Kuo, Y.-C. Chao, S.-Y. Tung, S.-S. Yang, J.-H. Kao, C.-H. Liu, W.-W. Su, C.-L. Lin, Y.-M. Jeng, P.-J. Chen, D.-S. Chen
Journal: Journal of Hepatology (2009)
Successful treatment of childhood intramedullary spinal cord astrocytomas with irinotecan and cisplatin
Authors: Jaume Mora, Ofelia Cruz, Sandra Gala, Ramon Navarro
Journal: Neuro-Oncology (2006)

Childhood spinal cord astrocytomas are rare diseases, and their management is controversial. We report here our successful experience using irinotecan and cisplatin in three consecutive infants with progressing intramedullary astrocytomas. The first patient was a 16-month-old girl who presented with a grade III intramedullary astrocytoma that rapidly progressed after surgery and adjuvant chemotherapy. Weekly irinotecan (50 mg/m(2)) and cisplatin (30 mg/m(2)) for four consecutive weeks (one cycle) for a total of four cycles (I/C regimen) was used in order to avoid or delay radiotherapy. Radiological complete remission was achieved 10 months after completion of therapy, and 3.5 years after diagnosis the patient remains disease free. The second patient was a 19-month-old boy with a C3-T4 grade II intramedullary astrocytoma who received up-front vincristine and carboplatin for two months but remained clinically symptomatic. A followup MRI showed a larger tumor, and the patient was switched to the I/C regimen. A marked clinical improvement occurred after the first cycle, and MRI showed a very good partial remission at the end of therapy. At 16 months after diagnosis, the patient remains disease free. The third patient was a 10-month-old girl with a C2-T3 grade II intramedullary astrocytoma. She presented with severe pain that became steroid dependent during the month she was treated with the vincristine-carboplatin regimen. When she was switched to the I/C regimen, the clinical symptoms responded within days. MRI at the end of therapy showed a significant reduction in tumor size, and one year after diagnosis the patient remains symptom free. Using this I/C regimen for childhood intramedullary astrocytoma, we obtained remarkable clinicoradiological responses while avoiding the use of radiotherapy.
Nanotheranostics ˗ Application and Further Development of Nanomedicine Strategies for Advanced Theranostics
Authors: Madaswamy S. Muthu, David Tai Leong, Lin Mei, Si-Shen Feng
Journal: Theranostics (2014)

Nanotheranostics is to apply and further develop nanomedicine strategies for advanced theranostics. This review summarizes the various nanocarriers developed so far in the literature for nanotheranostics, which include polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles, carbon nanotubes, and nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents for better theranostic effects with fewer side effects. The theranostic nanomedicine can achieve systemic circulation, evade host defenses and deliver the drug and diagnostic agents at the targeted site to diagnose and treat the disease at cellular and molecular level. The therapeutic and diagnostic agents are formulated in nanomedicine as a single theranostic platform, which can then be further conjugated to biological ligand for targeting. Nanotheranostics can also promote stimuli-responsive release, synergetic and combinatory therapy, siRNA co-delivery, multimodality therapies, oral delivery, delivery across the blood-brain barrier as well as escape from intracellular autophagy. The fruition of nanotheranostics will be able to provide personalized therapy with bright prognosis, which makes even the fatal diseases curable or at least treatable at the earliest stage.
Circulating Dopamine and C-Peptide Levels in Fasting Nondiabetic Hypertensive Patients
Authors: Andreas Tomaschitz, Eberhard Ritz, Katharina Kienreich, Burkert Pieske, Winfried März, Bernhard O. Boehm, Christiane Drechsler, Andreas Meinitzer, Stefan Pilz
Journal: Diabetes Care (2012)

Accumulating evidence supports a potential role for dopamine in the regulation of insulin secretion. We examined the association between circulating dopamine and C-peptide concentrations using data from the Graz Endocrine Causes of Hypertension (GECOH) study.After 12 h of fasting, we measured plasma dopamine and serum C-peptide levels and established determining factors of insulin secretion in 201 nondiabetic hypertensive patients (mean age 48.1 ± 16.0 years; 61.7% women).Mean dopamine and C-peptide concentration were 33.4 ± 38.6 pg/mL and 3.1 ± 2.7 ng/mL, respectively. A strong and inverse correlation was observed between dopamine and C-peptide levels (r = -0.423, P < 0.001). There was no significant relationship between C-peptide, plasma epinephrine, and norepinephrine. C-peptide levels decreased steadily and significantly from tertile 1 of dopamine (3.6 ng/mL [95% CI 2.9-4.1]) to tertile 3 (1.6 ng/mL [1.5-2.7], P < 0.001) after multivariate adjustment.The inverse association between dopamine and C-peptide highlights the need to evaluate whether dopamine could be effective for modulating endocrine pancreatic function.
Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells
Authors: H Gal, N Amariglio, L Trakhtenbrot, J Jacob-Hirsh, O Margalit, A Avigdor, A Nagler, S Tavor, L Ein-Dor, T Lapidot, E Domany, G Rechavi, D Givol
Journal: Leukemia (2006)
Aging Enhances the Sensitivity of Endothelial Cells Toward Apoptotic Stimuli
Authors: Jörg Hoffmann, Judith Haendeler, Alexandra Aicher, Lothar Rössig, Mariuca Vasa, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation Research (2001)

Advanced aging leads to impaired endothelial NO synthesis and enhanced endothelial cell apoptosis; therefore, we investigated the sensitivity of aged endothelial cells toward apoptotic stimuli and determined the role of NO. Human umbilical vein endothelial cells (HUVECs) were cultured until 14th passage. In aged cells, oxLDL and tumor necrosis factor-alpha-induced apoptosis and caspase-3-like activity were significantly enhanced more than 3-fold compared with young cells (passage 3). Because NO contributes to protection against endothelial cell death via S-nitrosylation of caspases, we determined endothelial NO synthase (eNOS) protein expression and the content of S-nitrosylated proteins. Aged HUVECs showed significantly reduced eNOS expression (35+/-10%) and a decrease in the overall S-NO content (33+/-3%), suggesting that eNOS downregulation may be involved in age-dependent increase of apoptosis sensitivity. Indeed, eNOS knockout endothelial cells showed a significantly enhanced apoptosis induction. Exogenous NO donors abolished increased apoptosis and caspase-3-like activity. In contrast, the application of shear stress, which exerts a profound apoptosis inhibitory effect via upregulation of NO synthesis in young cells, failed to inhibit apoptosis in aged cells. Moreover, no upregulation of eNOS protein expression and S-NO content in response to shear stress was detected in aged cells. Overexpression of wild-type eNOS completely restored the antiapoptotic effect of shear stress, whereas only a partial inhibitory effect was detected under steady conditions. Strikingly, transfection of constitutively active phosphomimetic eNOS (S1177D) further abrogated apoptosis in aged HUVECs. Thus, aging of endothelial cells is associated with decreased NO synthesis and concomitantly increased sensitivity of apoptosis, which may contribute to functional impairment of the endothelial monolayer.
Invisible Barriers to Clinical Trials: The Impact of Structural, Infrastructural, and Procedural Barriers to Opening Oncology Clinical Trials
Authors: David M. Dilts, Alan B. Sandler
Journal: Journal of Clinical Oncology (2006)

To investigate the administrative barriers that impact the opening of clinical trials at the Vanderbilt-Ingram Cancer Center (VICC) and at VICC Affiliate Network (VICCAN) sites.VICC, a National Cancer Institute-designated comprehensive cancer center, and three VICCAN community practice sites were studied. Methodology used was identification and mapping of existing processes and analysis of historical timing data.At course granularity, the process steps required at VICC and VICCAN main office plus local sites are 20 v 17 to 30 steps, respectively; this gap widens with finer granularity, with more than 110 v less than 60 steps, respectively. Approximately 50% of the steps are nonvalue added. For example, in the institutional review board (IRB) process, less than one third of the steps add value to the final protocol. The numbers of groups involved in the approval processes are 27 (VICC) and 6 to 14 (VICCAN home office and local sites). The median times to open a trial are 171 days (95% CI, 158 to 182 days) for VICC and 191 days (95% CI, 119 to 269 days) for the VICCAN sites. Contrary to expectations, the time for IRB review and approval (median, 47 days) is the fastest process compared with the scientific review committee review and approval (median, 70 days) and contracts and grants review (median, 78.5 days). Opening a cooperative group clinical trial is significantly (P = .05) more rapid because they require fewer review steps.There are numerous opportunities to remove nonvalue-added steps and save time in opening clinical trials. With increasing numbers of new agents, fewer domestic principal investigators, and more companies off-shoring clinical trials, overcoming such barriers is of critical importance for maintenance of core oncology research capabilities in the United States.
Role of Noncoding RNA ANRIL in Genesis of Plexiform Neurofibromas in Neurofibromatosis Type 1
Authors: Eric Pasmant, Audrey Sabbagh, Julien Masliah-Planchon, Nicolas Ortonne, Ingrid Laurendeau, Lucie Melin, Salah Ferkal, Lucie Hernandez, Karen Leroy, Laurence Valeyrie-Allanore, Béatrice Parfait, Dominique Vidaud, Ivan Bièche, Laurent Lantieri, Pierre Wolkenstein, Michel Vidaud
Journal: JNCI Journal of the National Cancer Institute (2011)

Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome with a worldwide birth incidence of one in 2500. Genetic factors unrelated to the NF1 locus are thought to influence the number of plexiform neurofibromas (PNFs) in patients with NF1, but no factors have been identified to date. We used high-resolution array comparative genomic hybridization of tissue from 22 PNFs obtained from 18 NF1 patients to identify modifier genes involved in PNF development. We used a family-based association test for five previously identified cancer-susceptibility tag single-nucleotide polymorphisms (rs1063192, rs2151280, rs2218220, rs10757257, and rs7023329) located in chromosomal region 9p21.3 in 1105 subjects (740 NF1 patients and 365 non-affected relatives) from 306 families. To confirm the functional role of rs2151280, we used real-time quantitative reverse transcription–polymerase chain reaction to analyze the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A), CDKN2B, alternate reading frame (ARF), and antisense noncoding RNA in the INK4 locus (ANRIL) in the peripheral blood of 124 NF1 patients. Relationships between CDKN2A, CDKN2B, ARF, and ANRIL expression and the rs2151280 genotype were tested by the Kruskal–Wallis test. All statistical tests were two-sided. In NF1-associated PNFs, 9p21.3 deletions (including the CDKN2A/B-ANRIL locus) were found as the only recurrent somatic alterations. Single-nucleotide polymorphism rs2151280 (located in ANRIL) was statistically significantly associated with the number of PNFs (P < .001) in NF1 patients. In addition, allele T of rs2151280 was statistically significantly associated with reduced ANRIL transcript levels (P < .001), suggesting that modulation of ANRIL expression mediates PNF susceptibility. Identification of ANRIL as a modifier gene in NF1 may offer clues to the molecular pathogenesis of PNFs, particularly neurofibroma formation, and emphasizes the unanticipated role of large noncoding RNA in activation of critical regulators of tumor development.