tbuckley/cabot-search huggingface dataset:
An Enzyme-Linked Immunosorbant Assay (ELISA) for Detecting Antimitochondrial Antibody
Authors: Marshall M. Kaplan, John V. Gandolfo, Elaine G. Quaroni
Journal: Hepatology (1984)

We have developed an enzyme linked immunosorbant assay (ELISA) for antimitochondrial antibody. Polyvinyl microtiter plate wells are coated with partially purified rat kidney mitochondria, and excess protein binding sites are blocked with bovine serum albumin. Human serum, diluted 1:1,000, is incubated for 1 hr. Then β-galactosidase-goat-anti-human IgG (H+L) is added followed by the substrate, p-nitrophenyl-β-D-galactopyranoside. The plates are then read at 404 nM in a microelisa autoreader. A positive result was defined as optical density ± 0.100, more than 5 standard deviations above the mean of 36 normal individuals. With this techique, 56 of 60 patients with primary biliary cirrhosis were positive for antimitochondrial antibody (93%), mean O.D., 0.456 ± 0.031 S.E. Seventeen of 17 patients with extrahepatic bile duct obstruction and 14 or 14 patients with alcoholic cirrhosis were negative. Only 1 of 29 patients with chronic active liver disease was positive (4%). Antinuclear antibody and antimicrosomal antibody do not bind in this assay, and activity is absorbed from sera by preincubation with suspensions of rat kidney mitochondria. The ELISA is approximately 20 times more sensitive than a quantitive microtiter complement fixation technique and more convenient than radioimmunoassay. It is rapid, quantitative and uses stable reagents. In contrast to immunofluorescence techniques, it is not affected by observer interpretation.
Occurrence of oval-type cells in hepatitis B virus—associated human hepatocarcinogenesis
Authors: Chu Chieh Hsia, Ritva P. Evarts, Harushige Nakatsukasa, Elizabeth R. Marsden, Snorri S. Thorgeirsson
Journal: Hepatology (1992)

Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma.
Optimization of Dosing for EGFR-Mutant Non–Small Cell Lung Cancer with Evolutionary Cancer Modeling
Authors: Juliann Chmielecki, Jasmine Foo, Geoffrey R. Oxnard, Katherine Hutchinson, Kadoaki Ohashi, Romel Somwar, Lu Wang, Katherine R. Amato, Maria Arcila, Martin L. Sos, Nicholas D. Socci, Agnes Viale, Elisa de Stanchina, Michelle S. Ginsberg, Roman K. Thomas, Mark G. Kris, Akira Inoue, Marc Ladanyi, Vincent A. Miller, Franziska Michor, William Pao
Journal: Science Translational Medicine (2011)

Predictive models of EGFR-mutant tumor behavior point to alternative drug dosing strategies to prevent and treat acquired resistance.
CLONAL GROWTH OF MAMMALIAN CELLS IN VITRO
Authors: Theodore T. Puck, Philip I. Marcus, Steven J. Cieciura
Journal: The Journal of Experimental Medicine (1956)

Two methods for simple and rapid plating of single HeLa cells, human, carcinomatous cells, are described. These result in growth and formation of colonies from each single cell. One of these procedures uses irradiated, non-multiplying "feeder" cells to condition the medium. The second requires more gentle handling of the cells, but otherwise is virtually the same as that used in plating bacteria on semisolid, nutrient media. By extension of these methods, it is possible to isolate single mutant colonies and grow pure clonal stocks of animal cells. These genetically uniform strains are much more homogeneous in their behavior than the parental HeLa cell population. Growth curves obtained from developing colonies are highly reproducible. The most active mutant stocks so far isolated display a generation time of 18 to 20 hours. In pooled human serum HeLa cells assume a highly stretched, ameboid form, with marked motility; whereas growth of the same cells in a variety of non-human sera results in tightly packed, columnar, epithelial-like morphology. The two cell types possess volumes, nuclear cross-sections, plating efficiencies, and generation times which are identical within experimental error, but display widely different cross-sectional areas, suggesting that the basic change occurs in the cell surface. It is conceivable that this change may be related to that which enables the cells of a compact tumor to become invasive. Animal cells subjected to the standard trypsinization procedures which involve mechanical trauma and repeated washings in incomplete media leak large amounts of P and suffer impaired ability to reproduce as isolated cells. Application of the methods described in this paper as a tool for quantitative study of normal mammalian cell growth, physiology, genetics, and biochemistry, and the response of cells to drugs, viruses, high energy radiation, and other agents have been indicated.
A Mechanism of Transition From Ventricular Fibrillation to Tachycardia
Authors: Faramarz H. Samie, Ravi Mandapati, Richard A. Gray, Yoshio Watanabe, Charlotte Zuur, Jacques Beaumont, José Jalife
Journal: Circulation Research (2000)

Abbreviation of the action potential duration and/or effective refractory period (ERP) is thought to decrease the cycle length of reentrant arrhythmias. Verapamil, however, paradoxically converts ventricular fibrillation (VF) to ventricular tachycardia (VT), despite reducing the ERP. This mechanism remains unclear. We hypothesize that the size and the dynamics of the core of rotating waves, in addition to the ERP, influence the arrhythmia manifestation (ie, VF or VT). The objectives of this study were (1) to demonstrate functional reentry as a mechanism of VF and VT in the isolated Langendorff-perfused rabbit heart in the absence of an electromechanical uncoupler and (2) to elucidate the mechanism of verapamil-induced conversion of VF to VT. We used high-resolution video imaging with a fluorescent dye, ECG, frequency and 2-dimensional phase analysis, and computer simulations. Activation patterns in 10 hearts were studied during control, verapamil perfusion (2x10(-6) mol/L), and washout. The dominant frequency of VF decreased from 16.2+/-0.7 to 13.5+/-0.6 Hz at 20 minutes of verapamil perfusion (P<0.007). Concomitantly, phase analysis revealed that wavefront fragmentation was reduced, as demonstrated by a 3-fold reduction in the density of phase singularities (PSs) on the ventricular epicardial surface (PS density: control, 1.04+/-0.12 PSs/cm(2); verapamil, 0.32+/-0.06 PSs/cm(2) [P=0.0008]). On washout, the dominant frequency and the PS density increased, and the arrhythmia reverted to VF. The core area of transiently appearing rotors significantly increased during verapamil perfusion (control, 4.5+/-0.6 mm(2); verapamil, 9.2+/-0.5 mm(2) [P=0.0002]). In computer simulations, blockade of slow inward current also caused an increase in the core size. Rotating waves underlie VF and VT in the isolated rabbit heart. Verapamil-induced VF-to-VT conversion is most likely due to a reduction in the frequency of rotors and a decrease in wavefront fragmentation that lessens fibrillatory propagation away from the rotor.
Five-Year Follow-Up of the Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease (ERACI II)
Authors: Alfredo E. Rodriguez, Julio Baldi, Carlos Fernández Pereira, Jose Navia, Máximo Rodriguez Alemparte, Alejandro Delacasa, Federico Vigo, Daniel Vogel, William O'Neill, Igor F. Palacios
Journal: Journal of the American College of Cardiology (2005)
Including Walnuts in a Low-Fat/Modified-Fat Diet Improves HDL Cholesterol-to-Total Cholesterol Ratios in Patients With Type 2 Diabetes
Authors: Linda C. Tapsell, Lynda J. Gillen, Craig S. Patch, Marijka Batterham, Alice Owen, Marian Baré, Meredith Kennedy
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to examine the effect of a moderate-fat diet inclusive of walnuts on blood lipid profiles in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—This was a parallel randomized controlled trial comparing three dietary advice groups each with 30% energy as fat: low fat, modified low fat, and modified low fat inclusive of 30 g of walnuts per day. Fifty-eight men and women, mean age 59.3 ± 8.1 years, started the trial. Dietary advice was given at baseline with monthly follow-up and fortnightly phone calls for support. Body weight, percent body fat, blood lipids, HbA1c, total antioxidant capacity, and erythrocyte fatty acid levels were measured at 0, 3, and 6 months. Data were assessed by repeated-measures ANOVA with an intention-to-treat model. RESULTS—The walnut group achieved a significantly greater increase in HDL cholesterol–to–total cholesterol ratio (P = 0.049) and HDL (P = 0.046) than the two other treatment groups. A 10% reduction in LDL cholesterol was also achieved in the walnut group, reflecting a significant effect by group (P = 0.032) and time (P = 0.036). There were no significant differences between groups for changes in body weight, percent body fat, total antioxidant capacity, or HbA1c levels. The higher dietary polyunsaturated fat–to–saturated fat ratio and intakes of ω-3 fatty acids in the walnut group were confirmed by erythrocyte biomarkers of dietary intake. CONCLUSIONS—Structured “whole of diet” advice that included 30 g of walnuts/day delivering substantial amounts of polyunsaturated fatty acid improved the lipid profile of patients with type 2 diabetes.
The impact of fractional exhaled nitric oxide (FeNO) measurement on treatment decision making in the specialist care of established asthma
Authors: Craig LaForce, Nancy Herje, Paul Dorinsky
Journal: European Respiratory Journal (2013)

Introduction: Assessment of FeNO) provides a measure of Th2 airway inflammation that cannot be provided by other routinely asthma assessment tools. In fact, spirometry and asthma control tests (ACT) or questionnaires (ACQ) don9t inform about airway inflammation.  Objective: To determine the ability of physicians to assess airway inflammation using standard clinical tools and assess how FeNO levels effect treatment decision making by asthma specialists.  Methods: A total of 50 subjects ages 7-60 years with asthma were recruited at a asthma and allergy specialty practice. Patients underwent routine clinical assessment including spirometry and ACT testing. Physicians then clinically assessed airway inflammation as low, intermediate, high or unknown and determined a treatment plan. Subjects then underwent FeNO testing and the results were provided to the physicians who then had an opportunity to modify the asthma treatment plan.  Results: Physician judgment on the level of airway inflammation was incorrect in 51.2% and correct in 48.8%. Of note, airway inflammation was low in 8 of 50 subjects in whom physicians assessed it as intermediate or high and was high in 9 of 50 subjects in whom physicians assessed it as low or intermediate. Importantly, treatment decisions were substantially altered in 40% of subjects following FeNO determination.  Conclusions: Clinical assessments by asthma specialists were inadequate for assessing airway inflammation. These results have important effectiveness and cost implications for asthma management since FeNO determinations substantially impacted treatment decision making in 40% patients.
Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial
Authors: Douglass A Morrison, Gulshan Sethi, Jerome Sacks, William Henderson, Frederick Grover, Steven Sedlis, Rick Esposito, Kodangudi Ramanathan, Darryl Weiman, Jorge Saucedo, Tamim Antakli, Venki Paramesh, Stuart Pett, Sarah Vernon, Vladimir Birjiniuk, Frederick Welt, Mitchell Krucoff, Walter Wolfe, John C Lucke, Sundeep Mediratta, David Booth, Charles Barbiere, Daniel Lewis
Journal: Journal of the American College of Cardiology (2001)
Measuring health in pulmonary hypertension: emphasising the right end-point?
Authors: Mardi Gomberg-Maitland, Hubert Chen
Journal: European Respiratory Journal (2014)

Pulmonary hypertension (PH) is a condition deriving from multiple aetiologies with the recent focus on Group 1 pulmonary arterial hypertension (PAH) and Group 4 chronic thromboembolic pulmonary hypertension (CTEPH) largely due to the surge of understanding in pathophysiology and resultant treatments available [1]. Both are a disease of the pulmonary circulation that is characterised by a progressive rise in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), with limited dysfunction of the left ventricle [2]. Symptoms manifest as patients’ lose the ability to augment their cardiac output in the face of a fixed vascular resistance [3]. In addition, anxiety and depression disorders are highly prevalent in PAH and CTEPH patients and correlate with the patients’ sense of wellness [4]. However, despite therapeutic options and overall improved outcomes, life expectancy is shortened [5, 6] and patients must face the myriad of issues that go along with a chronic debilitating fatal disease [7–9].

The definition of “good health” is not just the absence of disease but also incorporates emotional and physical security, a sense of contentment. The World Health Organization first formally acknowledged this concept in the 1952 …
Acute upper gastrointestinal bleeding: identifying low risk patients
Authors: G Chakrabarty, C Groves, R Pollok
Journal: Gut (2011)

We read with interest the article by Hearnshaw et al 1 regarding the outcomes in acute upper gastrointestinal (GI) bleeding. The study re-enforces the importance of the Rockall score in stratifying patients at high risk. We are interested to …
Comprehensive Genetic Analysis of Complement and Coagulation Genes in Atypical Hemolytic Uremic Syndrome
Authors: Fengxiao Bu, Tara Maga, Nicole C. Meyer, Kai Wang, Christie P. Thomas, Carla M. Nester, Richard J. H. Smith
Journal: Journal of the American Society of Nephrology (2013)

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy caused by uncontrolled activation of the alternative pathway of complement at the cell surface level that leads to microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. In approximately one half of affected patients, pathogenic loss-of-function variants in regulators of complement or gain-of-function variants in effectors of complement are identified, clearly implicating complement in aHUS. However, there are strong lines of evidence supporting the presence of additional genetic contributions to this disease. To identify novel aHUS-associated genes, we completed a comprehensive screen of the complement and coagulation pathways in 36 patients with sporadic aHUS using targeted genomic enrichment and massively parallel sequencing. After variant calling, quality control, and hard filtering, we identified 84 reported or novel nonsynonymous variants, 22 of which have been previously associated with disease. Using computational prediction methods, 20 of the remaining 62 variants were predicted to be deleterious. Consistent with published data, nearly one half of these 42 variants (19; 45%) were found in genes implicated in the pathogenesis of aHUS. Several genes in the coagulation pathway were also identified as important in the pathogenesis of aHUS. PLG, in particular, carried more pathogenic variants than any other coagulation gene, including three known plasminogen deficiency mutations and a predicted pathogenic variant. These data suggest that mutation screening in patients with aHUS should be broadened to include genes in the coagulation pathway.
The impact of preschool wheezing patterns on health-related quality of life at age 4 years
Authors: Esther Hafkamp-de Groen, Ashna D. Mohangoo, Jeanne M. Landgraf, Johan C. de Jongste, Liesbeth Duijts, Henriëtte A. Moll, Vincent W.V. Jaddoe, Albert Hofman, Hein Raat
Journal: European Respiratory Journal (2012)

We assessed whether dynamic preschool wheezing patterns affect health-related quality of life (HRQOL) at age 4 years. The study included 3878 children participating a prospective cohort study. Information on preschool wheezing was obtained by questionnaire and children were categorised into: never, early, late and persistent wheezing. At age 4 years HRQOL was measured using the Child Health Questionnaire (CHQ). Persistent wheezing was associated with reduced scores for nine out of 13 CHQ scales. No differences in psychosocial CHQ scores (p&gt;0.05), but lower physical CHQ scores were found in children with late and persistent wheezing, compared to children who never wheezed (p&lt;0.001). Mean scores on general health perceptions were, respectively, eight and 12 points lower (on a 0–100 scale) in children with late and persistent wheezing (p&lt;0.001), and children with one to three episodes and four or more episodes of wheezing in the fourth year respectively scored seven and 24 points lower (p&lt;0.001), compared to children who never wheezed. Persistent wheezing during preschool age independently affects a child's HRQOL, particularly general health perceptions and physical domains at age 4 years. HRQOL was more affected by frequent wheezing episodes in the fourth year of life, rather than by the duration of wheezing at age 0–4 years.
Vascular Endothelium As a Contributor of Plasma Sphingosine 1-Phosphate
Authors: Krishnan Venkataraman, Yong-Moon Lee, Jason Michaud, Shobha Thangada, Youxi Ai, Herbert L. Bonkovsky, Nehal S. Parikh, Cheryl Habrukowich, Timothy Hla
Journal: Circulation Research (2008)

Sphingosine 1-phosphate (S1P), an abundant lipid mediator in plasma, regulates vascular and immune cells by activating S1P receptors. In this report, we investigated the mechanisms by which high plasma S1P levels are maintained in mice. We found that plasma S1P turns over rapidly with a half-life of approximately 15 minutes, suggesting the existence of a high-capacity biosynthetic source(s). Transplantation of bone marrow from wild-type to Sphk1(-/-)Sphk2(+/-) mice restored plasma S1P levels, suggesting that hematopoietic cells are capable of secreting S1P into plasma. However, plasma S1P levels were not appreciably altered in mice that were thrombocytopenic, anemic, or leukopenic. Surprisingly, reconstitution of Sphk1(-/-)Sphk2(+/-) bone marrow cells into wild-type hosts failed to reduce plasma S1P, suggesting the existence of an additional, nonhematopoietic source for plasma S1P. Adenoviral expression of Sphk1 in the liver of Sphk1(-/-) mice restored plasma S1P levels. In vitro, vascular endothelial cells, but not hepatocytes, secreted S1P in a constitutive manner. Interestingly, laminar shear stress downregulated the expression of S1P lyase (Sgpl) and S1P phosphatase-1 (Sgpp1) while concomitantly stimulating S1P release from endothelial cells in vitro. Modulation of expression of endothelial S1P lyase with small interfering RNA and adenoviral expression altered S1P secretion, suggesting an important role played by this enzyme. These data suggest that the vascular endothelium, in addition to the hematopoietic system, is a major contributor of plasma S1P.
Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia
Authors: David L. Porter, Wei-Ting Hwang, Noelle V. Frey, Simon F. Lacey, Pamela A. Shaw, Alison W. Loren, Adam Bagg, Katherine T. Marcucci, Angela Shen, Vanessa Gonzalez, David Ambrose, Stephan A. Grupp, Anne Chew, Zhaohui Zheng, Michael C. Milone, Bruce L. Levine, Jan J. Melenhorst, Carl H. June
Journal: Science Translational Medicine (2015)

CAR T cells persist and sustain remissions in advanced chronic lymphocytic leukemia.
Aggressive treatment is appropriate for glioblastoma multiforme patients 70 years old or older: a retrospective review of 206 cases
Authors: J. G. Scott, J. H. Suh, P. Elson, G. H. Barnett, M. A. Vogelbaum, D. M. Peereboom, G. H. J. Stevens, H. Elinzano, S. T. Chao
Journal: Neuro-Oncology (2011)

Elderly patients have largely been excluded from randomized trials for glioblastoma multiforme (GBM). We reviewed the results of treatment approaches, which included surgery, chemotherapy, and radiation in this group of patients. Patients were treated during the period 1979-2007 and were 70 years of age and older with histologically confirmed GBM. Overall survival (OS) was the primary endpoint of this retrospective study. Two hundred six patients 70 years of age and older were identified. Median age was 75 years (range 70-90). Median OS time was 4.5 months. Univariate analysis showed that OS was significantly impacted by KPS score (1.8 months for KPS ≤ 50 to 17.2 months for KPS ≥ 90, P < .001), age at diagnosis (5.1 months for age 70-79 versus 3.1 months for age ≥ 80, P < .001), and extent of disease (worse for bilateral disease [P = .003], multifocal disease [P = .005], and multicentric disease [P = .02]). On multivariate analysis, higher KPS score (P = .006), surgical resection (any surgery beyond biopsy) (P < .001), radiation therapy (P < .001), and chemotherapy (P < .001) were all found to be independently associated with improved OS. In this study of newly diagnosed glioblastoma patients over the age of 70 years, aggressive treatment with radiation, chemotherapy, and surgery is associated with OS.
Catheter ablation of ventricular arrhythmias in nonischemic dilated cardiomyopathy patients
Authors: Niranjan Seshadri, Naveen Acharya, Ahmad Abdul-Karim, Stefan Bertog, Mina K. Chung, Walid Saliba, Robert Schweikert, Mark Niebauer, David O. Martin, Patrick J. Tchou
Journal: Journal of the American College of Cardiology (2002)
642 ASSOCIATION BETWEEN EPIDERMAL GROWTH FACTOR GENE 61AG POLYMORPHISM AND AGE AT THE DIAGNOSIS OF HEPATOCELLULAR CARCINOMA: IMPLICATIONS FOR SURVEILLANCE
Authors: C. Smirne, L. Franzosi, A. Magri, E. Boccato, E. Mossio, C. Marconi, R. Minisini, M. Pirisi
Journal: Journal of Hepatology (2013)