tbuckley/cabot-search huggingface dataset:
Utilization of a-Ketoglutarate for Synthesis of 2-Hydroxyglutarate Oncometabolite Promotes Catabolic Flexibility, Redox Perturbation and Mitochondrial Activity That Supports Chemoresistance in IDH1 Mutant Acute Myeloid Leukemia
Authors: Lucille Stuani, Christian Recher, Jean-Charles Portais, Jean-Emmanuel Sarry
Journal: Blood (2017)
Influence of aortic valve disease on systolic stiffness of the human left ventricular myocardium.
Authors: TWisenbaugh, J LElion, S ENissen
Journal: Circulation (1987)

The new concept of systolic myocardial stiffness was applied to the study of ejection mechanics in aortic valve disease. Frame-by-frame analysis of stress (sigma) and volume (V) was performed for two differently loaded beats in 26 patients who underwent simultaneous cineangiography and micromanometry: nine normal subjects, eight with isolated aortic regurgitation (AR), and nine with aortic stenosis (AS). Maximum myocardial stiffness (maxEav) was defined as the slope of the end-systolic (es) stress-strain relationship. End-systole was defined as the frame where stiffness was maximal, and strain was defined as epsilon = loge (Dm/Dom), where Dm is left ventricular midwall diameter and Dom is the theoretical Dm at zero stress. Expressed in terms of cavity volume, epsilon = gamma X loge (V/Vo), where gamma is the geometric factor relating Dm to V during systole. Vo was obtained by extrapolating to sigma es = 0 the function, sigma es = maxEav X gamma X loge (Ves/Vo), which was fit to the end-systolic data. Vo a...
Prostacyclin biosynthesis and phospholipase activity in hypoxic rat myocardium.
Authors: HKawaguchi, HYasuda
Journal: Circulation Research (1988)

Phospholipid metabolism was studied in rat myocardial slices that were incubated under normoxia or hypoxia for up to 24 hours. Phospholipid degradation was prominent in hypoxic myocardium, particularly phosphatidylcholine, which markedly decreased after 24 hours of hypoxia. In contrast, lysophosphatidylcholine increased. The mechanism of phospholipid degradation in hypoxic myocardium was studied. The highest activity for phospholipase A2 among subcellular fractions was found in microsomal fraction. In hypoxic myocardium, this phospholipase A2 activity markedly increased and had substrate specificity toward phosphatidylcholine and phosphatidylethanolamine. Phosphatidylcholine was slightly hydrolyzed in control myocardium, but it was markedly hydrolyzed in hypoxic myocardium. Phospholipase C activity was found in cytosol and had a high substrate specificity toward phosphatidylinositol. In hypoxic myocardium, its activity gradually decreased during hypoxic incubation. Prostacyclin biosynthesis was also deter...
Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences.
Authors: L ASiddoway, K AThompson, C BMcAllister, TWang, G RWilkinson, D MRoden, R LWoosley
Journal: Circulation (1987)

The relationship between debrisoquine metabolic phenotype and the pharmacokinetics and pharmacodynamics of propafenone was studied in 28 patients with chronic ventricular arrhythmias (22 extensive metabolizers [EMs] and six poor metabolizers [PMs] of debrisoquine). EMs were characterized by a shorter propafenone elimination half-life (5.5 +/- 2.1 vs 17.2 +/- 8.0, p less than .001), lower average plasma concentration (Cp) (1.1 +/- 0.6 vs 2.5 +/- 0.5 ng/ml/mg daily dosage, p less than .001), and higher oral clearance (1115 +/- 1238 vs 264 +/- 48 ml/min, p less than .001). The active metabolite 5-hydroxypropafenone, assayed in 12 patients, was identified in nine of 10 EMs but in neither of the PMs. A lower incidence of central nervous system side effects was noted in EMs (14% vs 67%, p less than .01). The magnitude of QRS widening at any given propafenone Cp was greater in EMs than PMs. There was no significant difference between EMs and PMs in effective propafenone dose or frequency of antiarrhythmic respon...
Characterization of the early lesion of 'degenerative' valvular aortic stenosis. Histological and immunohistochemical studies.
Authors: C MOtto, JKuusisto, D DReichenbach, A MGown, K DO'Brien
Journal: Circulation (1994)

BACKGROUNDNonrheumatic stenosis of trileaflet aortic valves, often termed senile or calcific valvular aortic stenosis, is considered a degenerative process, but little is known about the cellular or molecular factors that mediate its development.METHODS AND RESULTSTo characterize the developing aortic valvular lesion, we performed histological and immunohistochemical studies on Formalin-fixed and methanol-Carnoy's-fixed paraffin-embedded aortic valve leaflets or on frozen sections obtained at autopsy from 27 adults (age, 46 to 82 years) with normal leaflets (n = 6), mild macroscopic leaflet thickening (n = 15), or clinical aortic stenosis (n = 6). Focal areas of thickening (early lesions) were characterized by (1) subendothelial thickening on the aortic side of the leaflet, between the basement membrane (PAS-positive) and elastic lamina (Verhoeff-van Gieson), (2) the presence of large amounts of intracellular and extracellular neutral lipids (oil red O) and fine, stippled mineralization (von Kossa), a...
Detection of cardiac transplant rejection with radiolabeled lymphocytes.
Authors: S RBergmann, R ALerch, E MCarlson, J ESaffitz, B ESobel
Journal: Circulation (1982)

To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocy...
Development of pulmonary arteriovenous shunt after superior vena cava-right pulmonary artery (Glenn) anastomosis. Report of four cases.
Authors: R CMcFaul, A JTajik, D DMair, G KDanielson, J BSeward
Journal: Circulation (1977)

Four patients with cyanotic congenital heart disease who had previously undergone superior vena cava-right pulmonary artery (Glenn) anastomosis developed pulmonary arteriovenous malformations that resulted in significant intrapulmonary right-to-left shunting. This abnormality was documented by selective angiography, oximetry, and contrast echocardiogrphy. It may be a major cause of late clinical deterioration in patients treated with the Glenn anastomosis.
Double Dissection at the Cecum - Endoscopic Submucosal Dissection
Authors: DB Moura, N Nunes, M Flor de Lima, C Chálim Rebelo, MP Santos, V Costa Santos, AC Rego, JR Pereira, N Paz, MA Duarte
Journal: Endoscopy (2021)

Endoscopic submucosal dissection (ESD) results in high en-bloc resection rate. Male, 80 years old, two sessile polyps of 20 mm and 40 mm in the cecum (JNET 2A).A solution of carmine and adrenalin was injected, followed by mucosal incision. In the first, conventional submucosal dissection, the scar was closed with clips. In the second, submucosal dissection was performed by traction method.Histology revealed that the first was hyperplasic. The second was adenomatous, high grade dysplasia, negative margins.This case demonstrates ESD at the cecum. ESD has the potential to become the common therapy for large superficial colorectal sessile tumors.
Membrane currents and tension in cat ventricular muscle treated with cardiac glycosides.
Authors: T FMcDonald, HNawrath, WTrautwein
Journal: Circulation Research (1975)

The effect of cardiac glycosides on membrane currents and tension in cat ventricular muscle was studied using the single sucrose gap voltage clamp method. Complete tension-voltage and current-voltage relations were obtained in five preparations before and during treatment with dihydro-ouabain (DHO, 1.7 X 10(-5)M). After 1-2 minutes of DHO, the developed tension was 15% greater than control, but there was no change in either the slow inward (calcium) current (Ica) or the level of the outward current flowing at the end of a 300-msec depolarization (Iout). After 6-8 minutes of DHO, there was a 60% increase in developed tension, a noticeable increase in resting tension, a 20% decrease in Ica, and a smaller increase in Iout. It seems possible that the reduction of Ica was due to a reduced driving force. In preparations treated with ouabain (5 X 10(-7)M, 3-5 minutes), developed tension was 45-150% greater than control with no change in Ica or Iout between -45 and + 15 mv. We conclude that the inotropic action o...
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Authors:  Thomas
Journal: JAMA Oncology (2015)

Nancy E. Thomas, MD, PhD; Sharon N. Edmiston, BS; Audrey Alexander, BS; Pamela A. Groben, MD; Eloise Parrish, MS; Anne Kricker, PhD; Bruce K. Armstrong, MBBS, DPhil; Hoda Anton-Culver, PhD; Stephen B. Gruber, MD, MPH, PhD; Lynn From, MD; Klaus J. Busam, MD; Honglin Hao; Irene Orlow, PhD; Peter A. Kanetsky, MPH, PhD; Li Luo, PhD; Anne S. Reiner, MPH; Susan Paine, MPH; Jill S. Frank, MS; Jennifer I. Bramson; Lorraine D. Marrett, PhD; Richard P. Gallagher, MA; Roberto Zanetti, MD; Stefano Rosso, MD, MSc; Terence Dwyer, MD; Anne E. Cust, PhD; David W. Ollila, MD; Colin B. Begg, PhD; Marianne Berwick, MPH, PhD; Kathleen Conway, PhD; for the GEM Study Group
Active transport and inotropic state in guinea pig left atrium.
Authors: PLechat, C RMalloy, T WSmith
Journal: Circulation Research (1983)

Although the positive inotropic effect of cardiac glycosides correlates well with inhibition of Na+ pump activity in many preparations, digitalis at low concentrations (10(-9) to 10(-8) M) may produce an apparent stimulation of monovalent cation transport in isolated intact myocardium or produce an inotropic effect that does not correlate with pump inhibition. Digitalis is known to modify tissue metabolism of endogenous neurotransmitters that may affect inotropic state, Na,K-ATPase activity, and K+ permeability. We examined the interactions of low concentrations of ouabain with adrenergic and cholinergic influences in isolated guinea pig left atria stimulated at 3.3 Hz in which inotropic state and monovalent cation transport (measured as 86Rb+ uptake) were assessed simultaneously. Ouabain (10(-9) M) stimulated Rb+ transport (+25%) without an inotropic response; the stimulatory effect on transport was abolished by propranolol or atropine pretreatment. In atria pretreated with atropine, 10(-8) M ouabain pro...
Mechanism of vascular hyperresponsiveness in the spontaneously hypertensive rat.
Authors: L TLais, M JBrody
Journal: Circulation Research (1975)

Hyperresponsiveness of resistance vessels has been described in various vascular beds of spontaneously hypertensive rats perfused with artificial medium. This change has been attributed to altered vascular dimensions secondary to the development of hypertension. To test the possibility that true changes in sensitivity might contribute independently to vasoconstrictor hyperresponsiveness in spontaneously hypertensive rats, threshold vasoconstrictor doses of norepinephrine and barium chloride were determined in denervated hindquarters of rats perfused at constant flow with autologous blood. Threshold constrictor responses to norepinephrine were elicited in the hypertensive rats at concentrations averaging less than one-third that required in controls. Threshold vasoconstrictor concentrations of barium were not significantly different between the two groups. The ratio of norepinephrine/barium sensitivity was also significantly elevated in the hypertensive group. These data suggest that in the presence of a f...
Excess Deaths From COVID-19 and Other Causes in the US, March 1, 2020, to January 2, 2021
Authors: Steven H. Woolf, Derek A. Chapman, Roy T. Sabo, Emily B. Zimmerman
Journal: JAMA (2021)

Steven H. Woolf, MD, MPH; Derek A. Chapman, PhD; Roy T. Sabo, PhD; Daniel M. Weinberger, PhD; Latoya Hill, MPH
Unanswered Questions Concerning Locoregional Irradiation in Breast Cancer
Authors: Pelagia G. Tsoutsou, Olalla Santa Cruz Gonzalez
Journal: JAMA Oncology (2016)

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Collecting and banking human milk
Authors: B. Bjorksten, B. Fredrikzon, O. Hernell, P. de Chateau
Journal: BMJ (1981)

Background: MicroRNAs are regulators of gene expression implicated in vital cellular processes including differentiation, cell growth and apoptosis. Distinct microRNA signatures have been identified for many malignancies including follicular lymphoma (FL). However, no microRNA expression profile characteristic of FL subtypes, e.g. FL with B-cell lymphoma-6 (BCL6) locus rearrangement (FL<sup>BCL2+/BCL6+</sup>, FL<sup>BCL2−/BCL6+</sup>) or FL with diffuse growth pattern have been reported. Materials and Methods: MicroRNA signatures from 44 cases of FL were generated employing a quantitative real-time polymerase chain reaction approach. 15 cases of diffuse FL and 15 cases of FL<sup>BCL2+/BCL6+</sup>/FL<sup>BCL2−/BCL6+</sup> were compared against 14 cases of typical FL<sup>BCL2+/BCL6−</sup>. Results: Numerous microRNAs were found to be differentially expressed between FL<sup>BCL2+/BCL6+</sup> and FL<sup>BCL2−/BCL6+</sup>, as well as diffuse FL, when compared to typical cases of FL. Up-regulation of several oncogenic microRNAs as well as down-regulation of tumor-suppressor microRNAs was identified. Cluster analysis, however, revealed no microRNA signatures distinct from the reference group for either subtype. Conclusion: These results indicate an involvement of microRNAs in the pathogenesis of FL and its subtypes. Marked de-regulation of oncogenic RNAs and tumor suppressors appears to correspond with a more aggressive phenotype frequently observed in FL<sup>BCL2+/BCL6+</sup>, FL<sup>BCL2−/BCL6+</sup> and diffuse FL.
Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment.
Authors: C LWolfe, R ESievers, F LVisseren, T JDonnelly
Journal: Circulation (1993)

BACKGROUNDAlthough previous investigators have demonstrated that myocardial preconditioning reduces infarct size, the mechanisms of cardioprotection associated with preconditioning are not completely understood.METHODS AND RESULTSTo test the hypothesis that preconditioning (four 5-minute episodes of ischemia each followed by 5 minutes of reperfusion) reduces infarct size by depleting cardiac glycogen stores and attenuating the degree of intracellular acidosis during subsequent prolonged left coronary artery occlusion, preconditioned and control rats were subjected to 45 minutes of left coronary artery occlusion and 120 minutes of reflow immediately after preconditioning (groups 1P and 1C, respectively) or after 30 minutes (groups 2P+30m and 2C), 1 hour (groups 3P+60m and 3C), or 6 hours (groups 4P+360m and 4C) of nonischemic recovery after preconditioning but before prolonged ischemia. In each group, cardiectomy was performed in selected rats immediately before prolonged ischemia for cardiac glycogen assa...
Response to Letter Regarding Article, “Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials.”
Authors: Azmil H. Abdul-Rahim, Ana-Cristina Perez, Rachael L. Fulton, Pardeep S. Jhund, Roberto Latini, Gianni Tognoni, John Wikstrand, John Kjekshus, Gregory Y. H. Lip, Aldo P. Maggioni, Luigi Tavazzi, Kennedy R. Lees, John J.V. McMurray
Journal: Circulation (2015)
Prediction of multivessel disease after inferior myocardial infarction.
Authors: B RChaitman, D DWaters, FCorbara, M GBourassa
Journal: Circulation (1978)

We correlated clinical parameters with angiographic findings in 108 men with a previous isolated inferior myocardial infarction, to determine if these parameters could predict accurately which patients had multivessel disease. Of 71 men in angina class 2-3, 42 had three vessel disease versus only seven of the 37 who were either asymptomatic or angina class 1 (P less than 0.001). Multivessel disease was present in 35 of the 36 who had anterior ST-T abnormalities at rest (P less than 0.001) and 16 of the 17 with cardiomegaly. Among men 55 years and older, the incidence of multivessel disease was 94% compared to 70% in men less than 55 (P less than 0.03). We conclude that functional angina class, age, and the presence of resting anterior ST and T abnormalities are highly predictive of associated left system disease in survivors of inferior infarction.
Intraluminal flow-initiated hyperpolarization and depolarization shift the membrane potential of arterial smooth muscle toward an intermediate level.
Authors: J ABevan, G CWellman
Journal: Circulation Research (1993)

We examined the effect of intraluminal flow of physiological saline on the membrane potential of vascular smooth muscle cells in isolated rabbit cerebral arteries. Intraluminal flow (20 microL/min) caused a depolarization of 4.8 +/- 0.7 mV in muscle cells with a resting membrane potential of -62.5 +/- 1.2 mV (n = 19). However, when cells were depolarized to -48.7 +/- 1.8 mV using histamine and serotonin, the response to intraluminal flow was the opposite, a hyperpolarization of 5.6 +/- 1.0 mV (n = 9). These opposing effects of flow on membrane potential appear to balance at -57.8 +/- 1.1 mV (n = 31). Our results suggest that intraluminal flow may affect the level of basal tone present in arteries in vivo through modulating the membrane potential of vascular smooth muscle cells by concurrently activated depolarization and hyperpolarization.
Emerging Infectious Diseases — Learning from the Past and Looking to the Future
Authors: Christopher Elias, John N. Nkengasong, Firdausi Qadri
Journal: New England Journal of Medicine (2021)

Interview with Dr. Christopher Elias on progress in containing infectious diseases and steps for preventing and countering new threats. (09:26)Download Remarkable progress has been made in preventing deaths from infectious diseases. Now, attention could shift to focusing more resources on pandemic preparedness, including detecting and containing emerging zoonotic threats while they are localized and manageable.
Risk stratification of patients with non-Q wave myocardial infarction. The critical role of ST segment depression. The Diltiazem Reinfarction Study Research Group.
Authors: K BSchechtman, R JCapone, R EKleiger, R SGibson, D JSchwartz, RRoberts, P MYoung, W EBoden
Journal: Circulation (1989)

One-year follow-up data on 515 patients who survived hospitalization with MB-creatine kinase-confirmed, acute non-Q wave myocardial infarction were analyzed for factors related to mortality (n = 57) and late reinfarction (n = 64). Twelve of 24 analyzed variables were significantly associated with mortality. Those factors, which were independently predictive of mortality by Cox regression analysis, were  ST depression (p = 0.0009), a history of congestive heart failure (CHF) (p = 0.0069), older age (p = 0.0128), and ST elevation at hospital discharge (p = 0.0173). In-hospital reinfarction achieved borderline significance (p = 0.0512). Mortality during the follow-up period was 5.5% in patients with no ST depression, 10.1% in those with ST depression at baseline or discharge, and 22.2% in patients with ST depression at baseline and discharge (i.e., persistent ST depression). The age-adjusted risk of mortality for patients with  ST depression, discharge-ST elevation, and CHF was 13.99 ti...
Medicine and South Africa
Authors: M. Birnstingl, D. Black, C. Booth, S. Cassidy, C. Clarke, J. Davis, R. Doll, J. Havard, R. Hoffenberg, J. Horder, J. Humphrey, F. A. Jones, M. King, D. Morley, D. Morris, I. Munro, A. Storr, P. Wall, J. Walton
Journal: BMJ (1986)
Antenatal corticosteroids to reduce preterm deaths in low-income settings
Authors: Stephen Kaliti
Journal: The Lancet Global Health (2014)

The Comment by Kishwar Azad and Anthony Costello opposing scaleup of antenatal corticosteroids misdirects the discussion of this topic towards speculation about differences in low-income settings. Our experience in Malawi provides a concrete example of the rapid scaling up of antenatal corticosteroid treatment with dexamethasone. Malawi has the highest estimated preterm birth rate worldwide. In Bwaila Maternity Hospital, Lilongwe, that has more than 15 000 deliveries annually with more than 2900 preterm, we increased targeted coverage of antenatal corticosteroids from 8% to 80% in 16 weeks in women at risk of preterm delivery from 24 to 34 weeks’ gestation. After this pilot study, we began programmes in three other hospitals, reaching 59–83% coverage from a baseline of 1–6% within 6 weeks. This intervention has thus far been associated with a drop in preterm neonatal mortality contribution from 60% to 24% at 0–6 days of age. Although this intervention was not done as part of a trial, and focuses only on quality improvement, we noted no increase in the rate of maternal or neonatal infections. Antenatal corticosteroids induce fetal lung maturation through the same biological mechanism in low-income settings as in high-income settings and reduce the need for neonatal mechanical ventilation. Although antenatal corticosteroids might not be a so-called magic bullet as a standalone vertical intervention, no biological basis exists to presume that babies born preterm in resource-poor settings will succumb to respiratory distress syndrome any more than do those in resource-rich countries. I support the existing recommendation of a singlecourse of antenatal corticosteroids to mothers at high risk of preterm birth between 24 weeks and 33 weeks’ gestation, but question Azad and Costello’s unrealistic prerequisite for round-the-clock access to level 2 care in a low-income setting. Low-income settings, which have the highest burden of preterm neonatal deaths, urgently need proven benefi cial interventions, not the assessment of therapeutic efficacy on the basis of resource profi ling that could delay treatment. Contrary to Azad and Costello’s speculation, antenatal corticosteroids are likely to have a greater eff ect in the absence of level 2 care, not a lesser eff ect. The diff erence between low-income and high-income settings is not biology, but an increased burden of disease and reduced access to even basic health care. Our experience in Malawi off ers a powerful example for generalising this standard of care to the regions where it will save the most lives and also reduce neonatal disability.