tbuckley/cabot-search huggingface dataset:
Nuclear Magnetic Resonance Studies of Cancer. V. Appearance and Development of a Tumor Systemic Effect in Serum and Tissues 2
Authors: Donald P. Hollis, Leon A. Saryan, James S. Economou, Joseph C. Eggleston, Jeffrey L. Czeisler, Harold P. Morris
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Nuclear Magnetic Resonance Studies of Cancer. V. Appearance and Development of a Tumor Systemic Effect in Serum and Tissues Get access Donald P. Hollis, Donald P. Hollis 3Department of Physiological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, Md. 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Leon A. Saryan, Leon A. Saryan 3Department of Physiological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, Md. 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar James S. Economou, James S. Economou 3Department of Physiological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, Md. 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph C. Eggleston, Joseph C. Eggleston 5Department of Pathology, The Johns Hopkins University School of Medicine. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeffrey L. Czeisler, Jeffrey L. Czeisler 3Department of Physiological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, Md. 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold P. Morris Harold P. Morris 6Department of Biochemistry, Howard University College of Medicine, Washington, D.C. 20001. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 3, September 1974, Pages 807–815, https://doi.org/10.1093/jnci/53.3.807 Published: 01 September 1974 Article history Received: 26 February 1974 Accepted: 30 May 1974 Published: 01 September 1974
Prospects for adenovirus-mediated gene therapy of inherited diseases of the myocardium
Authors: N Bowles
Journal: Cardiovascular Research (1997)

Time for primary review 30 days.

Many genetic loci linked to a variety of diseases have been identified, and disease-causing mutations characterized. These have included diseases of the myocardium, such as X-linked dilated cardiomyopathy [1–3], hypertrophic cardiomyopathy [4–6], and Long QT syndrome [7–9]. The elucidation of gene defects has allowed different therapeutic strategies to be proposed, including the use of pharmaceutical agents to replace or to antagonize the mutated protein, and replacement of the defective gene with a functional one (gene therapy). There have been many publications describing the use of vectors to transduce target cells for the correction of gene defects or for anti-viral therapy (for reviews see [10–14]). Such vectors have included recombinant retroviruses, adenoviruses, adeno-associated viruses, and herpes viruses, as well as non-viral vectors. Each vector has inherent advantages and disadvantages. At this time the adenoviruses are most commonly used and represent the most likely vector for efficient transduction of the myocardium. While many groups have reported the use of recombinant adenoviruses to transduce cells in vitro and in vivo, and even their use in clinical trials for the correction of the cystic fibrosis gene defect [15, 16], there have been few reports describing the targeted expression of gene products for the correction of myocardial diseases. In this review we will discuss the potential of gene therapeutic approaches for the treatment of myocardial disease, as well as consider some of the limitations and risks associated with the use of the adenovirus-based vectors.

Recombinant adenoviruses have been the most commonly utilized vectors for the transduction of cells both in vitro and in vivo. This has primarily been due to their ability to be propagated and purified to high titers, their ability to transduce non-dividing cells, and their broad spectrum of target tissues. Most studies … 

* Corresponding author. Pediatric Cardiology, Baylor College of Medicine, One Baylor Plaza, Room 333E, Houston TX 77030, USA. Tel.: +1 713 7987342; Fax: +1 713 7988085; E-mail: jtowbin@bcm.tmc.edu
Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock
Authors: Lars B Holst, Nicolai Haase, Jørn Wetterslev, Jan Wernerman, Anne B Guttormsen, Sari Karlsson, Pär I Johansson, Anders Aneman, Marianne L Vang, Robert Winding, Lars Nebrich, Helle L Nibro, Bodil S Rasmussen, Johnny R M Lauridsen, Jane S Nielsen, Anders Oldner, Ville Pettilä, Maria B Cronhjort, Lasse H Andersen, Ulf G Pedersen, Nanna Reiter, Jørgen Wiis, Jonathan O White, Lene Russell, Klaus J Thornberg, Peter B Hjortrup, Rasmus G Müller, Morten H Møller, Morten Steensen, Inga Tjäder, Kristina Kilsand, Suzanne Odeberg-Wernerman, Brit Sjøbø, Helle Bundgaard, Maria A Thyø, David Lodahl, Rikke Mærkedahl, Carsten Albeck, Dorte Illum, Mary Kruse, Per Winkel, Anders Perner
Journal: New England Journal of Medicine (2014)

Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established.In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization.We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups.Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).
Outcome of Patients With Low-Gradient “Severe” Aortic Stenosis and Preserved Ejection Fraction
Authors: Nikolaus Jander, Jan Minners, Ingar Holme, Eva Gerdts, Kurt Boman, Philippe Brudi, John B. Chambers, Kenneth Egstrup, Y. Antero Kesäniemi, William Malbecq, Christoph A. Nienaber, Simon Ray, Anne Rossebø, Terje R. Pedersen, Terje Skjærpe, Ronnie Willenheimer, Kristian Wachtell, Franz-Josef Neumann, Christa Gohlke-Bärwolf
Journal: Circulation (2011)

Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area < 1.0 cm² and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient "severe" stenosis (defined as aortic valve area < 1.0 cm² and mean gradient ≤ 40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.Outcome in patients with low-gradient "severe" aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm²; mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67 ± 10 years; ejection fraction, ≥ 55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182 ± 64 versus 212 ± 68 g; P < 0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (P = 0.37; major cardiovascular events, 50.9% versus 48.5%, P = 0.58; cardiovascular death, 7.8% versus 4.9%, P = 0.19). Low-gradient severe stenosis patients with reduced stroke volume index (≤ 35 mL/m²; n = 223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P = 0.53).Patients with low-gradient "severe" aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis.
Abstract 1121: ER-negative breast cancer survive mitochondrial IMS-stress via SIRT3 activation
Authors: Luena Papa, Shahar Shimonovoch, Doris Germain
Journal: Cancer Research (2012)

Abstract Mitochondrial dysfunction is central in carcinogenesis and has been associated with elevated levels of Reactive Oxygen Species (ROS). While moderate levels of ROS activate signaling cascade promoting tumor progression, high levels of ROS can lead to cell death. We previously demonstrated that Estrogen Receptor (ER)-positive breast cancer cells activate ER to overcome the mitochondrial impairment and reduce high levels of ROS induced by stress in the inter-mitochondrial membrane space (IMS). The ultimate outcome of ER activation is induction of a novel Unfolded Protein Response (UPR) that involves up-regulation of NRF-1, a major regulator of mitochondrial biogenesis as well as induction of OMI and proteasome, two critical elements of protein quality control required to monitor the quality of IMS proteins. In the present work, we have evidence that ER-negative breast cancer cells trigger a distinct mechanism to cope up with IMS-stress. Due to the lack of ER, the stress from the IMS is extended into the matrix of mitochondria leading to activation of the matrix deacetylase, SIRT3. SIRT3 is required to increase the antioxidant capacity by up-regulating the antioxidant enzyme, MnSOD and therefore reducing ROS. In addition, our results reveal that SIRT3 is essential for removal of the irreversible impaired mitochondria through mitophagy. Overall, our data indicate that ER-positive and ER-negative breast cancer induce different mechanism to conquer mitochondrial malfunction coupled with ROS overproduction and maintain their cellular integrity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1121. doi:1538-7445.AM2012-1121
Chronic Protein Kinase B (PKB/c-akt) Activation Leads to Apoptosis Induced by Oxidative Stress–Mediated Foxo3a Transcriptional Up-regulation
Authors: Ankie G.M. van Gorp, Karen M. Pomeranz, Kim U. Birkenkamp, Rosaline C-Y. Hui, Eric W-F. Lam, Paul J. Coffer
Journal: Cancer Research (2006)

Increased protein kinase B (PKB; c-Akt) activation is a hallmark of diverse neoplasias providing both proliferative and antiapoptotic survival signals. In this study, we investigated the effect of chronic PKB activation on cellular survival and proliferation using cytokine-dependent bone marrow-derived Ba/F3 cells, in which PKBalpha activation can be directly, and specifically, induced by addition of 4-hydroxytamoxifen (4-OHT). Direct activation of PKB rescued Ba/F3 cells from cytokine withdrawal-induced apoptosis; however, surprisingly, these antiapoptotic effects were short lived, cells only being protected for up to 48 hours. We observed that activation of PKB in survival factor-deprived cells led to a dramatic increase of Foxo3a on both the transcriptional and protein level leading to expression of its transcriptional targets Bim and p27(kip1). High levels of PKB activity result in increased aerobic glycolysis and mitochondrial activity resulting in overproduction of reactive oxygen species. To determine whether oxidative stress might itself be responsible for Foxo3a up-regulation, we utilized hydrogen peroxide (H(2)O(2)) as an artificial inducer of oxidative stress and N-acetylcysteine (NAC), a thiol-containing radical oxygen scavenger. Addition of NAC to the culture medium prolonged the life span of cells treated with 4-OHT and prevented the up-regulation of Foxo3a protein levels caused by PKB activation. Conversely, treatment of Ba/F3 cells with H(2)O(2) caused an increase of Foxo3a on both transcriptional and protein levels, suggesting that deregulated PKB activation leads to oxidative stress resulting in Foxo3a up-regulation and subsequently cell death. Taken together, our data provide novel insights into the molecular consequences of uncontrolled PKB activation.
Plasma Insulin Responses to Oral and Intravenous Glucose: Studies in Normal and Diabetic Subjects*
Authors: Michael J. Perley, David M. Kipnis
Journal: Journal of Clinical Investigation (1967)

The plasma insulin responses of normal weight and obese, diabetic, and nondiabetic subjects to intravenous glucose was only 30-40% of that seen after oral glucose, indicating that alimentary mechanism(s) in addition to the arterial blood sugar concentration regulate insulin secretion. Observations made in subjects with diverted portal circulation indicate that the alimentary insulinogenic mechanism is located in the intestinal tract. The insulinogenic potency of the alimentary and glycemic stimuli expressed in terms of insulin secretion per gram of glucose were remarkably similar within each group of individuals. Between these groups, however, there were considerable differences. Obesity, with or without associated diabetes, was associated with a true hypersecretory responsiveness, whereas diabetes was characterized, with or without obesity, by a marked impairment in insulin secretion. The experimental design used in these studies permitted quantitation of the magnitude of the glycemic component of an oral glucose load. As a consequence of impaired insulin secretion, a greater than normal proportion of the oral glucose load escapes initial hepatic extraction in the maturity-onset diabetic and enters the peripheral circulation. Therefore, in the noninsulin-requiring maturity-onset diabetic, the glycemic insulinogenic stimulus for a given oral glucose load is significantly greater than in normal subjects and accounts for the excessive plasma insulin responses observed late in the course of an oral glucose tolerance test.
"Pittsburgh Pneumonia Agent": A Bacterium Phenotypically Similar to <i>Legionella pneumophila</i> and Identical to the TATLOCK Bacterium
Authors: G. ANN HÉBERT, BERENICE M. THOMASON, PATRICIA P. HARRIS, MARTIN D. HICKLIN, ROGER M. McKINNEY
Journal: Annals of Internal Medicine (1980)

The "Pittsburgh pneumonia agent," isolated by Pasculle and co-workers from human lung tissue, has been cultured on artificial media and characterized. The "Pittsburgh" bacterium and the TATLOCK and HEBA bacteria have identical cultural, biochemical, and antigenic characteristics. They also have the same cellular fatty-acid composition, and DNA relatedness indicates that they belong to the same species.
Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study
Authors: Lloyd Mayer, William J Sandborn, Yuriy Stepanov, Karel Geboes, Robert Hardi, Michael Yellin, Xiaolu Tao, Li An Xu, Luisa Salter-Cid, Sheila Gujrathi, Richard Aranda, Allison Y Luo
Journal: Gut (2013)

<h3>Objective</h3> Interferon-γ-inducible protein-10 (IP-10 or CXCL10) plays a role in inflammatory cell migration and epithelial cell survival and migration. It is expressed in higher levels in the colonic tissue and plasma of patients with ulcerative colitis (UC). This phase II study assessed the efficacy and safety of BMS-936557, a fully human, monoclonal antibody to IP-10, in the treatment of moderately-to-severely active UC. <h3>Design</h3> In this 8-week, phase II, double-blind, multicentre, randomised study, patients with active UC received placebo or BMS-936557 (10 mg/kg) intravenously every other week. The primary endpoint was the rate of clinical response at Day 57; clinical remission and mucosal healing rates were secondary endpoints. Post hoc analyses evaluated the drug exposure–response relationship and histological improvement. <h3>Results</h3> 109 patients were included (BMS-936557: n=55; placebo: n=54). Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However, higher BMS-936557 steady-state trough concentration (C<sub>minss</sub>) was associated with increased clinical response (87.5% vs 37.0% (p&lt;0.001) for patients with C<sub>minss</sub> 108–235 μg/ml vs placebo) and histological improvements (73.0% vs 41.0%; p=0.004). Infections occurred in 7 (12.7%) BMS-936557-treated patients and 3 (5.8%) placebo-treated patients. 2 (3.6%) BMS-936557 patients discontinued due to adverse events. <h3>Conclusions</h3> Anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC. Higher drug exposure correlated with increasing clinical response and histological improvement. Further dose–response studies are warranted. <h3>Clinical Trial Registration Number:</h3> ClinicalTrials.gov NCT00656890.
A first genome assembly of the barley fungal pathogen Pyrenophora teres f. teres
Authors: Simon R Ellwood, Zhaohui Liu, Rob A Syme, Zhibing Lai, James K Hane, Felicity Keiper, Caroline S Moffat, Richard P Oliver, Timothy L Friesen
Journal: Genome biology (2010)

Pyrenophora teres f. teres is a necrotrophic fungal pathogen and the cause of one of barley's most important diseases, net form of net blotch. Here we report the first genome assembly for this species based solely on short Solexa sequencing reads of isolate 0–1. The assembly was validated by comparison to BAC sequences, ESTs, orthologous genes and by PCR, and complemented by cytogenetic karyotyping and the first genome-wide genetic map for P. teres f. teres. The total assembly was 41.95 Mbp and contains 11,799 gene models of 50 amino acids or more. Comparison against two sequenced BACs showed that complex regions with a high GC content assembled effectively. Electrophoretic karyotyping showed distinct chromosomal polymorphisms between isolates 0–1 and 15A, and cytological karyotyping confirmed the presence of at least nine chromosomes. The genetic map spans 2477.7 cM and is composed of 243 markers in 25 linkage groups, and incorporates simple sequence repeat markers developed from the assembly. Among predicted genes, non-ribosomal peptide synthetases and efflux pumps in particular appear to have undergone a P. teres f. teres-specific expansion of non-orthologous gene families. This study demonstrates that paired-end Solexa sequencing can successfully capture coding regions of a filamentous fungal genome. The assembly contains a plethora of predicted genes that have been implicated in a necrotrophic lifestyle and pathogenicity and presents a significant resource for examining the bases for P. teres f. teres pathogenicity.
Effects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure&lt;SUBTITLE&gt;The EVEREST Outcome Trial&lt;/SUBTITLE&gt;
Authors: Marvin A Konstam, Mihai Gheorghiade, John C Burnett, Liliana Grinfeld, Aldo P Maggioni, Karl Swedberg, James E Udelson, Faiez Zannad, Thomas Cook, John Ouyang, Christopher Zimmer, Cesare Orlandi
Journal: JAMA (2007)

ContextVasopressin mediates fluid retention in heart failure. Tolvaptan, a vasopressin V2 receptor blocker, shows promise for management of heart failure.ObjectiveTo investigate the effects of tolvaptan initiated in patients hospitalized with heart failure.Design, Setting, and ParticipantsThe Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study. The outcome trial comprised 4133 patients within 2 short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006, and followed up during long-term treatment.InterventionWithin 48 hours of admission, patients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n = 2061) for a minimum of 60 days, in addition to standard therapy.Main Outcome MeasuresDual primary end points were all-cause mortality (superiority and noninferiority) and cardiovascular death or hospitalization for heart failure (superiority only). Secondary end points included changes in dyspnea, body weight, and edema.ResultsDuring a median follow-up of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group died (hazard ratio, 0.98; 95% confidence interval [CI], 0.87-1.11; P = .68). The upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 (P&lt;.001). The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group patients (40.2%; hazard ratio, 1.04; 95% CI, 0.95-1.14; P = .55). Secondary end points of cardiovascular mortality, cardiovascular death or hospitalization, and worsening heart failure were also not different. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased. The Kansas City Cardiomyopathy Questionnaire overall summary score was not improved at outpatient week 1, but body weight and serum sodium effects persisted long after discharge. Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the 2 groups.ConclusionTolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure–related morbidity.Trial Registrationclinicaltrials.gov Identifier: NCT00071331Published online March 25, 2007 (doi:10.1001/jama.297.12.1319).