tbuckley/cabot-search huggingface dataset:
Mechanisms of contraction induced by human leukocytes in normal and atherosclerotic arteries.
Authors: AMügge, D DHeistad, R CPadgett, B JWaack, PDensen, J ALopez
Journal: Circulation Research (1991)

Activation of leukocytes results in the release of a variety of vasoactive substances that may modulate vascular tone. We studied the effect of human polymorphonuclear (PMN) and mononuclear (MONO) leukocytes on quiescent femoral arteries in vitro. Arteries were obtained from normal and atherosclerotic cynomolgus monkeys. In normal arteries, stimulation of PMNs (3 and 5 x 10(6) cells/ml) with either thrombin (5 units/ml) or complement C5a (0.5 micrograms/ml) resulted in endothelium-independent contraction (approximately 25% of maximum contraction with 80 mM KCl). Vasocontraction was augmented in the presence of superoxide dismutase (150 units/ml) and was significantly impaired in the presence of the hydroxyl radical scavengers mannitol (20 mM) and deferoxamine (1 mM). Catalase (1,200 units/ml) or L-alanine (20 mM) did not modify this effect of PMNs. In contrast to PMNs, vasocontraction in response to MONOs was not altered by the addition of radical scavengers. Pretreatment of PMNs and MONOs with indomethac...
Intra-Operative Enteroscopy: A Last Resort in Small Bowel Bleeding
Authors: M Costa, C Macedo, A Amaro, C Agostinho, M Ferreira, N Almeida, P Figueiredo
Journal: Endoscopy (2021)

Aims Only 5 % of gastrointestinal (GI) bleeding occur in the small bowel (SB) but it accounts for most obscure GI bleeding. The availability of new diagnostic tools like computed tomography enterography (CTE), capsule endoscopy (CE) and double balloon enteroscopy has led to a paradigm shift in SB bleeding management. We, herein, present a case in which the non-surgical approach was not feasible.
Effect of intravenous aminophylline on plasma levels of catecholamines and related cardiovascular and metabolic responses in man.
Authors: R EVestal, C EEiriksson, BMusser, L KOzaki, J BHalter
Journal: Circulation (1983)

Theophylline is thought to act by inhibiting the activity of phosphodiesterase, with a resultant increase in intracellular cyclic AMP. However, this concept is largely based on in vitro studies using concentrations of theophylline which greatly exceed therapeutic plasma concentrations. To investigate the relationship of the cardiovascular and metabolic effects of theophylline to activation of the sympathetic nervous system, i.v. aminophylline was administered to six healthy males under basal conditions. Each subject received four infusions. Mean theophylline concentrations (+/- SEM) of 4.5 +/- 0.2, 10.0 +/- 0.5, 14.0 +/- 0.5 and 20.0 +/- 1.2 micrograms/ml were achieved. Plasma epinephrine increased 262% (from 29 +/- 4 to 105 +/- 14 pg/ml, p less than 0.01) and plasma norepinephrine increased 64% (from 190 +/- 18 to 312 +/- 51 pg/ml, p less than 0.05) during the high-dose infusion. The increases in circulating catecholamines were dose-related (p less than 0.001 by analysis of variance). Dose-related increa...
Selective functional characteristics of rate-induced fatigue in rabbit atrioventricular node.
Authors: JBillette, RMétayer, MSt-Vincent
Journal: Circulation Research (1988)

The slowly developing rate-induced prolongation in atrioventricular nodal conduction time, termed  was selectively studied using specifically designed stimulation protocols in isolated rabbit heart preparations. A nodal recovery curve (A2H2 versus H1A2 intervals; nodal conduction time of each premature beat plotted against corresponding recovery time) was obtained before and after a stable and nearly maximum fatigue had been reached by driving the atrium for 5 minutes at a fast rate close to the upper limit of 1:1 nodal conduction. The fatigue uniformly prolonged all A2H2 intervals (12.3 +/- 1.3 msec) and systematically increased the minimum H1A2 interval at which complete nodal block occurred (24.8 +/- 4.0 msec) (p less than 0.01, n = 6). To study the rate and time dependence of fatigue, nodal conduction times were obtained during three rapid 5-minute pacings corresponding to 50%, 75%, and 100% shortening of the pacing interval in the 1:1 nodal conduction range. The respective maximum fatigue-i...
Muscle carnitine deficiency in patients with severe peripheral vascular disease.
Authors: GBrevetti, CAngelini, MRosa, RCarrozzo, SPerna, MCorsi, AMatarazzo, AMarcialis
Journal: Circulation (1991)

BACKGROUNDThis study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease.METHODS AND RESULTSNine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/...
Pharmacological Disruption of the Notch1 Transcriptional Complex Inhibits Tumor Growth by Selectively Targeting Cancer Stem Cells
Authors: Annamil Alvarez-Trotta, William Guerrant, Luisana Astudillo, Mohini Lahiry, Giulia Diluvio, Elena Shersher, Hugo Kaneku, David J. Robbins, Darren Orton, Anthony J. Capobianco
Journal: Cancer Research (2021)

In many human cancers, deregulation of the Notch pathway has been shown to play a role in the initiation and maintenance of the neoplastic phenotype. Aberrant Notch activity also plays a central role in the maintenance and survival of cancer stem cells (CSC), which underlie metastasis and resistance to therapy. For these reasons, inhibition of Notch signaling has become an exceedingly attractive target for cancer therapeutic development. However, attempts to develop Notch pathway-specific drugs have largely failed in the clinic, in part due to intestinal toxicity. Here, we report the discovery of NADI-351, the first specific small-molecule inhibitor of Notch1 transcriptional complexes. NADI-351 selectively disrupted Notch1 transcription complexes and reduced Notch1 recruitment to target genes. NADI-351 demonstrated robust antitumor activity without inducing intestinal toxicity in mouse models, and CSCs were ablated by NADI-351 treatment. Our study demonstrates that NADI-351 is an orally available and potent inhibitor of Notch1-mediated transcription that inhibits tumor growth with low toxicity, providing a potential therapeutic approach for improved cancer treatment. SIGNIFICANCE: This study showcases the first Notch1-selective inhibitor that suppresses tumor growth with limited toxicity by selectively ablating cancer stem cells.
Carotid baroreflex function in young men with borderline blood pressure elevation.
Authors: D LEckberg
Journal: Circulation (1979)

Carotid baroreflex function was assessed in 10 normotensive young men and 20 age-matched subjects with borderline hypertension (successive blood pressures above and below 140/90 mm Hg) by measuring sinus node responses to brief neck suction. Subjects with borderline hypertension were divided into two equal groups according to their average systolic arterial pressures. Baroreflex responses were reset to function at higher pressure levels than normal in subjects with mild borderline hypertension, but reflex sensitivity was normal. Responses were also reset in subjects with more severe borderline hypertension, but reflex was subnormal. The results suggest that a gradation of baroreflex responsiveness exists among patients classified as having borderline hypertension: Subnormal responsiveness was found in those subjects whose resting average systolic arterial pressure was greater than or equal to 140 mm Hg.
Demonstration of lateral and epicardial border zone salvage by flurbiprofen using an in vivo method for assessing myocardium at risk.
Authors: J RDarsee, R AKloner, EBraunwald
Journal: Circulation (1981)

The purposes of this investigation were (1) to develop an in vivo method of determining the myocardium at risk after experimental coronary occlusion; (2) to define the spatial geometry of the salvageable ischemic border zone; an (3) to assess the ability of flurbiprofen, an antiinflammatory agent, to protect ischemic myocardium from necrosis. Twenty-two open-chest dogs underwent left anterior descending coronary artery occlusion and were randomized to treated (flurbiprofen 1 mg/kg i.v. at 30 minutes and 4 hours after occlusion; n = 11) or control (saline; n = 11) groups. Six hours after occlusion, methylene blue, 3 ml/lg, was injected into the left atrium, and immediately thereafter the hearts were removed and sliced transversely. Areas not perfused by methylene blue (area at risk [Ar]) were traced, planimetered, and compared to the area of necrosis (An) after incubation in triphenyltetrazolium chloride. The Ar for the two groups were similar (control 28.2 +/- 2.6%; treated 25.2 +/- 2.3% of total left ven...
Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species.
Authors: GHasenfuss, L AMulieri, E MBlanchard, CHolubarsch, B JLeavitt, FIttleman, N RAlpert
Journal: Circulation Research (1991)

Alteration in crossbridge behavior and myocardial performance have been associated with myosin isoenzyme composition in animal models of myocardial hypertrophy or atrophy. In the hypertrophied human heart, myocardial performance is altered without significant changes in myosin isoenzymes. To better understand this discrepancy, isometric heat and force measurements were carried out in 1) control and volume-overload human myocardium, 2) control, pressure-overload, and hyperthyroid rabbit myocardium, and 3) control and hypothyroid rat myocardium. In control human myocardium, peak isometric twitch tension was 44.0 +/- 11.7 mN/mm2, and maximum rate of tension rise was 69.2 +/- 21.0 mN/sec.mm2. In volume-overload human myocardium, peak twitch tension and maximum rate of tension rise were reduced by 55% (p less than 0.05) and 65% (p less than 0.05), respectively. The average force-time integral of the individual crossbridge cycle, calculated by myothermal techniques, was increased by 85% (p less than 0.005) in v...
Neurogenic skeletal myopathy in patients with primary cardiomyopathy.
Authors: J RDarsee, D ONutter, L CHopkins, S BHeymsfield
Journal: Circulation (1979)

Eleven patients with hypertrophic obstructive cardiomyopathy and eight patients with idiopathic congestive cardiomyopathy underwent extensive neuromuscular studies to determine if a skeletal myopathy is associated with uncomplicated primary cardiomyopathy. The clinical examination revealed peripheral neuropathies in six patients, but no evidence of muscle weakness or atrophy. Nerve conduction studies demonstrated a neuropathy in five of these six and in one other patient: three were in the hypertrophic group and three in the congestive group. Seven patients had abnormal electromyography, but none had characteristic myopathic changes. Of these seven patients, muscle biopsies showed denervation in two patients in the congestive group and type II atrophy in two patients in the hypertrophic group. We found no evidence of primary skeletal muscle involvement; however, neuropathic features and biopsy changes of denervation were present in both groups.
Cumulative depletions of extracellular calcium in rabbit ventricular muscle monitored with calcium-selective microelectrodes.
Authors: D MBers, K TMacLeod
Journal: Circulation Research (1986)

Transient changes of extracellular free calcium in rabbit ventricular muscle under nonsteady state conditions were measured with double-barreled calcium microelectrodes. Resumption of stimulation after a rest interval produces a cumulative decrease of extracellular free calcium often by more than 10% (with bulk extracellular free calcium = 0.2 mM). The extracellular free calcium returns to the bulk value as a new steady state is achieved. The changes of extracellular free calcium recorded presumably represent net calcium uptake and loss by cardiac muscle cells. These cumulative extracellular free calcium depletions are blocked by 0.5 mM cobalt and 1 microM nifedipine and are increased to 167 +/- 11% of control by the calcium agonist Bay k 8644 (1 microM) and to 620 +/- 150% of control by increasing stimulus frequency from 0.2-2 Hz. Caffeine (10 mM) inhibits the cumulative extracellular free calcium depletions, probably by rendering the sarcoplasmic reticulum unable to accumulate calcium. It is proposed th...
Cellular basis of chronic ventricular remodeling after myocardial infarction in rats.
Authors: GOlivetti, J MCapasso, L GMeggs, E HSonnenblick, PAnversa
Journal: Circulation Research (1991)

To determine whether the hypertrophic response of the surviving myocardium after infarction leads to normalization of ventricular hemodynamics and wall stress, the left coronary artery was ligated in rats. One month later, the rats were killed. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium bordering and remote from the scar was documented by increases in myocyte cell volume per nucleus of 43% and 25%, respectively. These cellular enlargements resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), myocyte hypertrophy was 81% and 32% in the regions adjacent to and distant from the scar, respectively. A 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular perf...
Effectiveness of Ex-Vivo Porcine Simulator On Endoscopic Ultrasound-Guided Cystogastrostomy Using Lumen-Apposing Metal Stent (LAMS) Training
Authors: N Roshdy, A Taleb, M Ibrahim
Journal: Endoscopy (2021)

Aims Endoscopic ultrasound (EUS) guided cystogastrostomy is a well-established endoscopic technique. However, it is an advanced technique with a steep learning curve. This necessitates an ex-vivo simulator that would allow endoscopists to be adequately trained. This is a preliminary study done to assess the efficacy of a new simulator in providing training for the EUS-guided cystogastrostomy using lumen-apposing metal stents (LAMS) specifically, the Hot AXIOS™ system
Abstract 13000: Ca2+/Calmodulin-Dependent Protein Kinase II is Essential in the Acute Phase of Pressure Overload
Authors: Susanne Klatt, Maria J Baier, Lars S Maier, Adam G Rokita
Journal: Circulation (2018)

Background: Activation of Ca2+/Calmodulin-dependent protein kinase II (CaMKII) is established as a central intracellular trigger for developing various cardiac pathologies such as hypertrophy, hear...
Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation.
Authors: WLuo, I LGrupp, JHarrer, SPonniah, GGrupp, J JDuffy, TDoetschman, E GKranias
Journal: Circulation Research (1994)

Phospholamban is the regulator of the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum (SR), and it has been suggested to be an important determinant in the inotropic responses of the heart to beta-adrenergic stimulation. To determine the role of phospholamban in vivo, the gene coding for this protein was targeted in murine embryonic stem cells, and mice deficient in phospholamban were generated. The phospholamban-deficient mice showed no gross developmental abnormalities but exhibited enhanced myocardial performance without changes in heart rate. The time to peak pressure and the time to half-relaxation were significantly shorter in phospholamban-deficient mice compared with their wild-type homozygous littermates as assessed in work-performing mouse heart preparations under identical venous returns, afterloads, and heart rates. The first derivatives of intraventricular pressure (+/- dP/dt) were also significantly elevated, and this was associated with an increase in the affinity of the SR Ca(2+)-ATPase fo...
Risks of Postmenopausal Hormone Replacement
Authors: Frank E. Speizer
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Volume ejected in early systole. A sensitive index of left ventricular performance in coronary artery disease.
Authors: L LJohnson, KEllis, DSchmidt, M BWeiss, P JCannon
Journal: Circulation (1975)

Indices based on early systolic ejection rates are theoretically more sensitive to ventricular performance than indices based on the entire systolic ejection (SE) period (mean ejection phase indices-MEPI): mean systolic ejection rate (MSER), mean normalized systolic ejection rate (MNSER) and mean velocity of circumferential fiber shortening (MVcf). The volume ejected in early systole is an indicator of the early rate of ejection. Accordingly, ventricular volume changes were determined by ventriculographic analysis for each thrid of SE in ml/sec (SER), as normalized systolic ejection rate (NSER), and as percent of stroke volume (PSV). In ten  controls all these indices were higher in the first third compared to the other thirds of SE. Seven patients with diffuse ventricular disease had depressed values in the first third of SE. Despite normal ventriculograms and  MEPI, eight patients with left anterior descending coronary artery stenoses (greater than 60%) also had definitely depressed ejectio...
Cross-sectional echocardiographic characterization of aortic obstruction. 1. Supravalvular aortic stenosis and aortic hypoplasia.
Authors: A EWeyman, R LCaldwell, R AHurwitz, D AGirod, J CDillon, HFeigenbaum, DGreen
Journal: Circulation (1978)

Cross-sectional echocardiographic and cineangiographic studies of the left ventricular outflow tract and ascending aorta were performed in five patients with supravalvular aortic stenosis (four hourglass and one hypoplastic). Visualization of the area of obstruction was possible in each patient using the cross-sectional system. In each case the echocardiographically determined diameter at the level of obstruction was within 3 mm of the similar angiographic value. Assessment of the extent of the lesion was possible in four of five cases. In three of these four cases the echocardiographic measurement was within 5 mm of the angiographic measurement while in the fourth the obstruction was felt to involve the total ascending aorta by both techniques. Determination of percent decrease in LVOT diameter from the aortic anulus to the level of obstruction was useful in defining obstruction and estimating severity. Cross-sectional echocardiography is a valuable noninvasive method for evaluating the ascending aorta i...
Abstract 1147: Differential Roles of ROCK1 and ROCK2 in Ischemia-induced Revacularization
Authors: Ping-Yen Liu, Kensuke Noma, Chao-Yung Wang, Hong-Wei Wang, Ryuji Okamoto, James K Liao
Journal: Circulation (2007)

Background: Rho and Rho-associated kinase (ROCK) are the key regulators of focal adhesion, stress fiber formation, and cell motility. The contribution of the ROCK isoforms, ROCK1 and ROCK2, on angi...
Effects of a thromboxane A2 analogue and prostacyclin on lung fluid balance in newborn lambs.
Authors: KYoshimura, M LTod, K GPier, L JRubin
Journal: Circulation Research (1989)

We have previously shown that the pulmonary venoconstriction produced by a stable thromboxane A2 analogue (STA2) is attenuated by prostacyclin (PGI2), but PGI2 increases the STA2-induced edema. The present study was designed to determine the effects of STA2 and PGI2 on the fluid balance in isolated blood-perfused newborn lamb lungs. Vascular permeability was evaluated by use of the fluid filtration coefficient (Kf) and the osmotic reflection coefficient for total proteins (sigma, hematocrit-protein double indicator technique), and pulmonary capillary pressure (Pc) was estimated by the double occlusion technique. All lungs had a period of hydrostatic stress induced by elevation of the left atrial pressure from 5 to 20 mm Hg to promote fluid filtration, and the rate of lung weight gain (delta W/delta T) during this period was determined. Studies were made in four groups; before the hydrostatic stress, lungs were given 1) STA2 (50 micrograms, n = 6), 2) PGI2 (0.4 micrograms/kg/min, n = 6), 3) both PGI2 and S...
Extracellular Ca(2+)-dependent potentiation by cocaine of serotonin- and norepinephrine-induced contractions in rat vascular smooth muscle.
Authors: CWatanabe, HYamamoto, SKobayashi, HKanaide
Journal: Circulation Research (1993)

Using front-surface fluorometry, we determined the effects of cocaine on force and cytosolic Ca2+ concentration ([Ca2+]i) in the rat aorta. We also examined the effects of cocaine on 45Ca2+ influx. Cocaine (10(-7) to 10(-4) M) alone did not alter the resting level of [Ca2+]i and force. Cocaine (  10(-3) ...
Hemodynamics in humans during conventional and experimental methods of cardiopulmonary resuscitation.
Authors: R DSwenson, W DWeaver, R ANiskanen, JMartin, SDahlberg
Journal: Circulation (1988)

High-fidelity hemodynamic recordings of aortic and right atrial pressures and the coronary perfusion gradient (the difference between aortic and atrial pressure) were made in nine patients during cardiopulmonary resuscitation (CPR). Findings during conventional manual CPR were compared with those during high-impulse CPR (rate, 120 cycles/min with a shorter compression:relaxation ratio) as well as during pneumatic vest CPR with and without simultaneous ventilation and abdominal binding. Aortic peak pressure during conventional CPR averaged 61 +/- 29 mm Hg but varied widely (range, 39-126 mm Hg) among patients. Although the magnitude of improvement was modest, the high-impulse method was the only technique tested that significantly elevated both aortic peak pressure and the coronary perfusion gradient during cardiac arrest. During conventional CPR, aortic pressure rose from 61 +/- 29 to 80 +/- 39 mm Hg during high-impulse CPR, and the gradient rose from 9 +/- 11 to 14 +/- 15 mm Hg, respectively; p less than...