tbuckley/cabot-search huggingface dataset:
Identification of functional PGH2/TxA2 receptors on human endothelial cells.
Authors: K CKent, L JCollins, F TSchwerin, M KRaychowdhury, J AWare
Journal: Circulation Research (1993)

Although functional receptors for thromboxane A2 and prostaglandin H2 (TxA2/PGH2) have been identified in platelets and vascular smooth muscle cells, receptor-mediated events in human endothelial cells stimulated by these endoperoxides have not been shown. Using cultured endothelial cells harvested from human umbilical or saphenous veins, we measured the effect of the TxA2 mimetic U46619 on mobilization of cytoplasmic calcium ([Ca2+]i), as well as release of prostacyclin and expression of the proto-oncogene c-fos, intracellular events that have been linked to [Ca2+]i rise in stimulated endothelial cells. Addition of U46619 to confluent fura 2-loaded endothelial cells caused a concentration-dependent rise in intracellular [Ca2+]i, with agonist concentrations of 300 nM producing a maximal [Ca2+]i rise. This [Ca2+]i rise was a uniform response observed in all individual endothelial cells throughout the monolayer, as shown by microspectrofluorimetric visualization. Similar effects were seen with a structurall...
Pericardial adaptation in severe chronic pulmonary hypertension. An intraoperative transesophageal echocardiographic study.
Authors: D GBlanchard, H CDittrich
Journal: Circulation (1992)

BACKGROUNDThe pericardium both limits cardiac distension and accentuates ventricular interdependence. Although this effect appears minimal under normal circumstances, the pericardium markedly restricts acute cardiac enlargement. Animal studies have demonstrated gradual pericardial adaptation and expansion in chronic volume overload and cardiomegaly, but the pericardial response in humans with cardiac hypertrophy and enlargement has not been examined fully. To investigate this further, 14 patients with right ventricular hypertrophy and cardiomegaly secondary to chronic pulmonary thromboembolic disease and severe pulmonary hypertension were studied during pulmonary thromboendarterectomy.METHODS AND RESULTSSimultaneous intraoperative transesophageal Doppler echocardiography and direct biventricular hemodynamic measurements were performed at steady state immediately before and after pericardiotomy. All hemodynamic variables showed no significant change before and after pericardiotomy, including heart rate (76...
Visualization and measurement of the main bronchi by tomography as an objective indicator of thoracic situs in congenital heart disease.
Authors: J BPartridge, OScott, P BDeverall, F JMacartney
Journal: Circulation (1975)

When investigating complex congenital heart disease, determination of atrial situs is essential. Pathological studies have demonstrated that the best predictor of atrial situs is thoracic situs. To assess thoracic situs, bronchial tomography was performed in 92 patients with congenital heart disease. Sixty-four of these, without abnormalities of situs or cardiac position, formed 'normal' controls. The lengths of the left and right main bronchi were measured. When these were related to age, and the results analyzed statistically, linear discriminant equations resulted giving a chance of only 0.09% of misclassifying a bronchus of unknown morphology. The lowest ratio between bronchial lengths (BLR) in any individual was 1.71:1. These results were then used to assess thoracic situs in 17 patients with abnormal situs or CARDIAC POSITION. In 7 (2 with situs inversus), abdominal and thoracic situs agreed. Of 6 patients with bilateral left lung, 3 had an interrupted inferior vena cava. Of 4 patients with presumpt...
Phorbol ester increases calcium current and simulates the effects of angiotensin II on cultured neonatal rat heart myocytes.
Authors: ADöşemeci, R SDhallan, N MCohen, W JLederer, T BRogers
Journal: Circulation Research (1988)

The effects of increased protein kinase C activity were studied in neonatal rat myocytes grown in primary culture. The changes in mechanical and electrical behavior, as well as protein phosphorylation, that followed the apparent activation of protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined. As spontaneous beating frequency was increased minimally by 10 nM TPA and by 100% with 85 nM TPA, shortening amplitude, shortening velocity, and relaxation velocity decreased concomitantly. In contrast, 4-alpha-phorbol-12,13-didecanoate (alpha-PDD), which does not activate protein kinase C, had no effect on beating behavior at 800 nM. In voltage-clamped single myocytes, both steady-state and transient components of the cadmium-sensitive calcium current were increased by the addition of TPA (65 nM). Neither the time constant for the inactivation of the transient component of this calcium current nor the reversal potential was altered by TPA. The phosphorylation state of a d...
Correlation between scintigraphic evidence of regional sympathetic neuronal dysfunction and ventricular refractoriness in the human heart.
Authors: HCalkins, KAllman, SBolling, MKirsch, DWieland, FMorady, MSchwaiger
Journal: Circulation (1993)

BACKGROUNDDenervation supersensitivity has been proposed as a mechanism for the relation between ventricular arrhythmias and the sympathetic nervous system. Evaluation of this phenomenon in humans has become feasible only recently with the development of noninvasive scintigraphic methods for evaluating the pattern of sympathetic innervation. The purpose of this study was to determine if scintigraphic evidence of sympathetic neuronal dysfunction correlates with measurements of ventricular refractoriness and to evaluate the phenomenon of denervation supersensitivity in humans.METHODS AND RESULTSEleven patients with a history of sustained ventricular tachycardia or sudden cardiac death who were referred for placement of an implantable defibrillator participated in this study (seven men and four women; age, 51 +/- 18 years). Preoperative scintigraphic evaluation of the pattern of sympathetic innervation was performed with 11C-hydroxyephedrine in conjunction with positron emission tomography. At the time of su...
Attenuation of reflex forearm vasoconstriction by alpha-human atrial natriuretic peptide in men.
Authors: ATakeshita, TImaizumi, NNakamura, HHigashi, TSasaki, MNakamura, KKangawa, HMatsuo
Journal: Circulation Research (1987)

This study examined whether atrial natriuretic peptide (ANP) modulates reflex forearm vasoconstriction in humans. Synthetic alpha-human ANP (alpha-hANP) was infused at a rate of 0.03 microgram/kg/min in 8 healthy men (mean age 23 +/- 0.7 years, mean +/- SEM). The alpha-hANP decreased systolic blood pressure and central venous pressure (CVP) but did not significantly alter resting heart rate and forearm vascular resistance (FVR). The magnitudes of reflex increases in FVR during lower body negative pressure (LBNP) at -110, -20, and -40 mm Hg were less during infusion of alpha-ANP than those magnitudes during infusion of saline solution. The slope of the regression line relating changes in CVP and those in FVR was less during infusion of alpha-hANP than the slope during infusion of saline solution. Forearm vascular responses to intra-arterial infusion of norepinephrine at doses of 100, 200, and 500 ng/min did not significantly differ during infusion of alpha-hANP and saline solution. These results suggest th...
Glycoside inotropy in the absence of an increase in potassium efflux in the rabbit heart.
Authors: P APoole-Wilson, G ALanger
Journal: Circulation Research (1975)

The inotropic effect of 1.25 times 10(-6)M acetylstrophanthidin (ACS) and the influx and efflux of labeled potassium (42K+) were studied in the arterially perfused rabbit interventricular septum under control conditions and during respiratory acidosis. An increase in the CO2 content of the gas mixture with which the modified Ringer's solution was equilibrated from 5 to 30% reduced the perfusate pH from 7.37 to 6.66. The increment in developed tension in the presence of ACS was 3.0 +/- 0.2 g (n equals 10) under control conditions, but it was greater, 7.1 +/- 0.9 g (N equals 9) during acidosis (P less than less than 0.001). The net K+ loss due to an increase in K+ efflux was 1.8 +/- 0.2 mmoles/kg wet weight in control experiments but only 0.1 +/- 0.1 mmoles/kg net weight under acidotic conitions (P less than less than 0.001); in seven of nine experiments in respiratory acidosis, no increase in K+ efflux occurred despite a marked positive inotropy. In three septums, K+ influx was reduced by ACS during respir...
LinDA: linear models for differential abundance analysis of microbiome compositional data
Authors: Huijuan Zhou, Kejun He, Jun Chen, Xianyang Zhang
Journal: Genome biology (2022)

Abstract Differential abundance analysis is at the core of statistical analysis of microbiome data. The compositional nature of microbiome sequencing data makes false positive control challenging. Here, we show that the compositional effects can be addressed by a simple, yet highly flexible and scalable, approach. The proposed method, LinDA, only requires fitting linear regression models on the centered log-ratio transformed data, and correcting the bias due to compositional effects. We show that LinDA enjoys asymptotic FDR control and can be extended to mixed-effect models for correlated microbiome data. Using simulations and real examples, we demonstrate the effectiveness of LinDA.
High‐dimensional analysis defines multicytokine T‐cell subsets and supports a role for IL‐21 in atopic dermatitis
Authors: Tali Czarnowicki, Hyun Je Kim, Axel P. Villani, Jacob Glickman, Ester Del Duca, Joseph Han, Ana B. Pavel, Brian H. Lee, Adeeb H. Rahman, Miriam Merad, James G. Krueger, Emma Guttman‐Yassky
Journal: Allergy (2021)

Flow cytometry is a well-accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL-21 may be involved in inflammatory skin diseases but its role in AD is not well established.We studied T-cell polarization in the blood of 20 moderate-to-severe AD and 15 controls. Using CyTOF and an unsupervised analysis, we measured the frequencies and mean metal intensities of activated polar CD4+ /CD8+ T-cell subsets. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to analyze skin samples.Examining 24 surface, intracellular markers, and transcription factors, we identified six CD4+ and five CD8+ T-cell metaclusters. A CD4+ skin-homing IL-13+ monocytokine and a novel IL-13+ IL-21+ multicytokine metaclusters were increased in AD vs. controls (p < .01). While IL-13 signature characterized both clusters, levels were significantly higher in the IL-21+ group. Both clusters correlated with AD severity (r = 0.49, p = .029). Manual gating corroborated these results and identified additional multicytokine subsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression, displayed significantly increasedIL-21 counts and colocalization with IL-13/IL-4R in AD skin.A multicytokine signature characterizes moderate-to-severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL-21 signature in blood and skin hints for a potential pathogenic role of IL-21 in AD.
Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan
Authors: Ling-Yi Wang, Sung-Chao Chu, Yin Lo, Yen-Yun Yang, K. Arnold Chan
Journal: JAMA Network Open (2021)

The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels.To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs.This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019.Use of Bcr-AbL TKIs.Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs.Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex-matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81).These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.
Letter by Ferraro and Arbab-Zadeh Regarding Article, “Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials”
Authors: Richard Ferraro, Armin Arbab-Zadeh
Journal: Circulation (2021)

Bangalore et al 1 reported a lower risk of nonprocedural myocardial infarction with a routine revascularization versus an early conservative strategy in their meta-analysis of patients with stable coronary heart disease, but they do not acknowledge 2 major factors that may, in part or even entirely, explain this difference.Foremost, patients assigned to revascularization using percutaneous coronary intervention (PCI) routinely receive dual antiplatelet therapy (DAPT), whereas this is less common in patients assigned to the conservative arm.Throughout the trial period, fewer patients assigned to the conservative versus the invasive strategy in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial received DAPT, at times approaching a 2:1 ratio among participants.Similar large differences in the administration of DAPT were noted in the FAME-2 (Fractional Flow Reserve Versus Angiography for Multi-Vessel Evaluation-2) study.Given a 22% risk reduction of nonprocedural myocardial infarction in pooled data and 53% in high-risk patients, 2 disparate allocation of DAPT unequivocally favors the invasive arm.Thus, differences should be interpreted considering this bias.Revascularization with coronary artery bypass grafting, as opposed to PCI, is associated with lower risk of spontaneous myocardial infarction in selected patients. 3Although an analysis of ISCHEMIA suggested similar risk reduction for coronary artery bypass grafting and PCI, the association is confounded by the disproportional use of DAPT in the PCI group.The results should be presented separately for coronary artery bypass grafting and PCI while acknowledging the confounding relationship of DAPT use in the PCI arm.It should be also noted that procedure-related myocardial infarctions were restrictively defined in many of the included studies, for example, ISCHEMIA and FAME-2.When an alternative definition was applied in ISCHEMIA, a lower 5-year cumulative overall myocardial infarction rate was observed with the conservative strategy versus invasive (12.7% versus 15.4% [95% CI for difference, 0.3%-5.1%])-despite the unequal allocation of DAPT favoring the invasive arm.The authors emphasize lower "unstable" angina presentations with an invasive strategy, but unstable angina is a controversial concept-even considered obsolete by leaders in the field 4 -and thus should be avoided as a study end point.Furthermore, unblinded allocation of treatment adds another well-established bias against a conservative approach in this context. 5e believe that, without acknowledging these important considerations, the authors' report remains unbalanced.We are concerned that a subjective analysis of clinical trial data may result in exposing patients to potentially unwarranted procedures.
Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment.
Authors: VManninen, LTenkanen, PKoskinen, J KHuttunen, MMänttäri, O PHeinonen, M HFrick
Journal: Circulation (1992)

BACKGROUNDWe studied the joint effect of baseline triglyceride and lipoprotein cholesterol levels on the incidence of cardiac end points in the trial group (n = 4,081) of the Helsinki Heart Study, a 5-year randomized coronary primary prevention trial among dyslipidemic middle-aged men. The relative risks (RR) were calculated using Cox proportional hazards models with a dummy variable technique that allows simultaneous study of subgroup combinations from the placebo and treatment groups.METHODS AND RESULTSIn the placebo group (n = 2,045), the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio was the best single predictor of cardiac events. This ratio in combination with the serum triglyceride level revealed a high-risk subgroup: subjects with LDL-C/HDL-C ratio greater than 5 and triglycerides greater than 2.3 mmol/l had a RR of 3.8 (95% CI, 2.2-6.6) compared with those with LDL-C/HDL-C ratio less than or equal to 5 and triglyceride concentration less than or equ...
Catheter ablation of the atrioventricular junction: a report of the percutaneous mapping and ablation registry.
Authors: M MScheinman, TEvans-Bell
Journal: Circulation (1984)

An international registry was formed to collate data for patients undergoing attempted catheter ablation of the atrioventricular (AV) junction and insertion of a permanent pacemaker. Over the past 2 years, data was submitted for 127 patients who were followed for a mean of 9.9 +/- 8.2 months. The most common arrhythmia treated was chronic or paroxysmal atrial fibrillation or flutter (78 patients, 61%); the remainder had supraventricular tachycardia due to AV node reentry, ectopic atrial tachycardia, or incorporated an accessory pathway. A single shock of 150 to 400 J was effective in producing chronic third-degree AV block in 45 patients while two or more shocks were used in an additional 45 patients. There was no significant difference in the total cumulative energy used in successful and unsuccessful procedures. Immediate complications related to the shock included ventricular fibrillation (one patient), pericardial tamponade (one patient), and transient hypotension (one patient). No chronic sequelae oc...
Monoclonal antibody to L-selectin attenuates neutrophil accumulation and protects ischemic reperfused cat myocardium.
Authors: X LMa, A SWeyrich, D JLefer, MBuerke, K HAlbertine, T KKishimoto, A MLefer
Journal: Circulation (1993)

BACKGROUNDInteraction of CD11/CD18 located on neutrophil membranes with its endothelial counter-receptor, intercellular adhesion molecule-1, plays a major role in polymorphonuclear leukocyte (PMN)-mediated endothelial dysfunction and myocardial injury associated with ischemia and reperfusion. However, PMN-derived L-selectin, which is thought to play an early role in PMN rolling along the vascular endothelium, has not been studied in a setting of myocardial ischemia and reperfusion.METHODS AND RESULTSIn this study, we evaluated the effects of a monoclonal antibody against L-selectin, DREG-200, in a feline model of myocardial ischemia (1.5 hours) and reperfusion (4.5 hours). DREG-200 (1 mg/kg) or an isotype-matched IgG1 antibody, MAb R3.1, which does not cross-react in cats, was administered as a bolus 10 minutes before reperfusion. In MAb R3.1-treated cats, myocardial ischemia followed by reperfusion resulted in significant coronary vascular endothelial dysfunction, elevated cardiac myeloperoxidase activit...
Abstract 9985: Effect of Alirocumab in Patients With Recent Acute Coronary Syndrome According to Renal Function: A Prespecified Analysis of the ODYSSEY OUTCOMES Trial
Authors: Jose Tunon, Philippe G Steg, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Shaun G Goodman, J Wouter Jukema, Yong-Un Kim, Qian H Li, Christian Mueller, Alexander Parkhomenko, Robert Pordy, Piyamitr Sritara, Michael Szarek, Harvey D White, Andreas M Zeiher, Gregory G Schwartz
Journal: Circulation (2019)

Introduction: Statins reduce CV risk in ACS patients (pts) with non-dialysis chronic kidney disease, but we do not know if the benefit of PCSK9 inhibition after ACS is affected by renal dysfunction...
Acknowledging Angst: Research Ethics Consultation in Disclosing Experimental Research Results of Uncertain Benefit
Authors: Ryan Spellecy, Alan Nyitray
Journal: The American Journal of Bioethics (2021)

"Acknowledging Angst: Research Ethics Consultation in Disclosing Experimental Research Results of Uncertain Benefit." The American Journal of Bioethics, 21(4), pp. 104–105
Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure.
Authors: MYoshimura, HYasue, KOkumura, HOgawa, MJougasaki, MMukoyama, KNakao, HImura
Journal: Circulation (1993)

BACKGROUNDThe plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in relation to the severity of congestive heart failure (CHF). This study was designed to examine whether the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.METHODS AND RESULTSWe measured plasma levels of ANP and BNP in the aorta in 20 patients with mitral stenosis (MS) in whom atria are mainly overloaded, 30 patients with dilated cardiomyopathy (DCM) in whom both atria and ventricles are overloaded, and 20 control subjects during cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) was significantly higher in the MS and DCM groups (16.7 +/- 4.7 mm Hg and 15.1 +/- 7.7 mm Hg, respectively) than in the control group (7.2 +/- 1.1 mm Hg, p < 0.01), whereas there was no significant difference between the MS and DCM groups. Left ventricular end-diastolic pressure (LVEDP) was significantly higher...