tbuckley/cabot-search huggingface dataset:
Partial purification of a high molecular weight renin from hog kidney.
Authors: MLevine, K ELentz, J RKahn, F EDorer, L TSkeggs
Journal: Circulation Research (1976)

Previous investigators have reported finding a high molecular weight (HMW) renin in various species which is activated by acidification. Two laboratories have reported that a decrease in molecular weight of the renin accompanies the acidification step. This report describes the partial purification of an HMW renin from hog kidney extracts which had previously been acidified to pH 2.5. The HMW renin, with a molecular weight of 57,000-59,000, constitutes only a small, relatively constant fraction of the total renin isolated. Omission of the acidification step or initial acidification to pH 1.6 does not change the amount of HMW renin significantly. The HMW renin attacks the protein substrate to produce angiotensin at about one-fourth the rate expected, based upon the rate at which it cleaves the tetradecapeptide substrate or a model nonapeptide substrate. It is inactivated by antiserum to hog kidney renin prepared in dogs. It is less stable than hog renin when stored at 0 degrees C. The HMW renin has a pH op...
Patterns of disturbed myocardial perfusion in patients with coronary artery disease. Regional myocardial perfusion in angina pectoris.
Authors: A PSelwyn, GForse, KFox, AJonathan, RSteiner
Journal: Circulation (1981)

Fifty patients who presented with angina pectoris were studied to examine the disturbances of regional myocardial perfusion during stress. Each patient underwent 16-point precordial mapping of the ECG during an exercise test, and coronary and left ventricular angiography. Regional myocardial perfusion was assessed using an atrial pacing test and a short-lived radionuclide, krypton-81m. Eleven patients had negative exercise tests and uniform increases in myocardial activity of krypton-81m of 98 +/- 18.0% during pacing. Ten patients performed 30,000-43,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and increases in myocardial activity of krypton-81m to remote and jeopardized myocardium at the onset of pacing. However, further pacing produced a decrease in activity in the affected segment of 68.0 +/- 9.0% accompanied by ST-segment depression and angina. Twelve patients achieved 26,000-32,000 J in positive exercise tests and had significant coronary artery disease. Atrial pa...
Decreased number and affinity of rat atrial natriuretic peptide (6-33) binding sites in the subfornical organ of spontaneously hypertensive rats.
Authors: J MSaavedra, AIsrael, MKurihara, EFuchs
Journal: Circulation Research (1986)

Binding sites for rat atrial natriuretic peptide (6-33) were quantified by incubation of brain sections with (3-[125I]iodotyrosyl28) rat atrial natriuretic peptide (6-33), followed by autoradiography with computerized microdensitometry. Spontaneously hypertensive rats present lower numbers and lower affinity of binding sites than normotensive controls, Wistar-Kyoto rats, in the subfornical organ (binding capacity 61.7 +/- 8.9 and 124.3 +/- 10.7 fmol/mg protein; affinity constant 4.25 +/- 0.55 and 11.10 +/- 1.67 X 10(9) M-1, respectively). In the choroid plexus, hypertensive rats have lower numbers of sites than normotensive rats (binding capacity 72.7 +/- 10.5 and 173.6 +/- 22.8 fmol/mg protein, respectively), but there was no difference in the binding affinity (affinity constant 6.28 +/- 0.82 and 7.60 +/- 2.06 X 10(9) M-1, respectively). Our results suggest that discretely localized brain binding sites for rat atrial natriuretic peptide (6-33) may have a physiological function in genetically hypertensive...
Restricted secretion of a T-lymphocyte chemotactic cytokine by serotonin-stimulated cultured aortic endothelial cells.
Authors: H WFarber, D JBeer
Journal: Circulation Research (1991)

The diversity of biologically active molecules produced by vascular endothelium suggests that the endothelial cell is an active participant in numerous physiological responses, including those of the immune system. In fact, the accumulation of T lymphocytes at extralymphatic inflammatory foci represents a series of interactions between lymphocytes and vascular endothelial cells. These interactions, however, may be modulated by other factors, such as vasoactive amines. In the current study, we report that serotonin-stimulated cultured bovine aortic endothelial cells (BAECs) secrete a T-lymphocyte chemotactic cytokine (endothelial cell-derived lymphocyte chemotactic activity [ED-LCA]). Supernatants from BAECs incubated with 10(-7)-10(-4) M serotonin (5-hydroxytryptamine [5-HT]) enhanced T-cell migration, which peaked at 10(-5) M 5-HT (235 +/- 18% control migration). ED-LCA was not stored in an active form in BAECs; its secretion occurred within 60 minutes of exposure to 5-HT and was blocked by two different...
The natriuretic and hypotensive effects of potassium.
Authors: D BYoung, R EMcCaa, Y JPan, A CGuyton
Journal: Circulation Research (1976)

The chronic effects of potassium loading on sodium balance and related variables were studied in two groups of dogs. The first group was intact except for the presence of indwelling arterial and venous cannulas. On the 1st day, increasing daily potassium intake from a normal level (30 mEq/day) to 200 mEq/day produced a 0.47-mEq increase in plasma potassium with a 56% increase (P greater than 0.01) in sodium excretion in spite of a 58% increase in plasma aldosterone concentration. After 6 days of potassium loading the cumulative negative sodium balance averaged 44 mEq while 22Na space decreased 6.7% (P less than 0.025). In this group arterial pressure did not change measurably. The same experimental protocol was repeated in a second group of dogs that were chronically adrenalectomized and maintained on fixed levels of aldosterone (50 mug/day) and hydrocortisone (1 mg/day). With aldosterone levels held constant the same increase in potassium intake produced a 1st day increase in potassium concentration of 1...
Isolated noncompaction of left ventricular myocardium. A study of eight cases.
Authors: T KChin, J KPerloff, R GWilliams, KJue, RMohrmann
Journal: Circulation (1990)

Isolated noncompaction of left ventricular myocardium is a rare disorder of endomyocardial morphogenesis characterized by numerous, excessively prominent ventricular trabeculations and deep intertrabecular recesses. This study comprised eight cases, including three at necropsy. Ages ranged from 11 months to 22.5 years, with follow-up as long as 5 years. Gross morphological severity ranged from moderately abnormal ventricular trabeculations to profoundly abnormal, loosely compacted trabeculations. Echocardiographic images were diagnostic and corresponded to the morphological appearances at necropsy. The depths of the intertrabecular recesses were assessed by a quantitative echocardiographic X-to-Y ratio and were significantly greater than in normal control subjects (p less than 0.001). Clinical manifestations of the disorder included depressed left ventricular systolic function in five patients, ventricular arrhythmias in five, systemic embolization in three, distinctive facial dysmorphism in three, and fa...
Down‐Regulation of Dkk‐1 in Platelets of Patients With Axial Spondyloarthritis
Authors: Marcin Czepiel, Małgorzata Stec, Mariusz Korkosz, Zofia Guła, Przemysław Błyszczuk, Jarosław Baran, Maciej Siedlar
Journal: Arthritis & Rheumatology (2021)

Axial spondyloarthritis (SpA) is a chronic autoinflammatory disease with new bone formation, which is controlled by Wnt/β-catenin signaling. Dkk-1 is an inhibitor of the Wnt pathway, and in humans, platelets represent a major source of Dkk-1. This study was undertaken to investigate whether levels of Dkk-1 in serum and platelet expression of DKK1 messenger RNA (mRNA) and Dkk-1 protein are affected in patients with axial SpA compared to healthy controls.Forty-one patients with axial SpA and 35 healthy controls were enrolled in the study. Total serum Dkk-1 levels in all patients and healthy controls were measured by quantitative enzyme-linked immunosorbent assay. Platelet DKK1 mRNA was analyzed by quantitative reverse transcriptase-polymerase chain reaction in 20 patients with axial SpA and 20 controls, and Dkk-1 protein levels were measured by immunoblotting in 20 patients with axial SpA and 18 controls.We found a lower concentration of Dkk-1 in the serum from patients with axial SpA compared to the serum from healthy controls (P < 0.0001). Furthermore, the expression of Dkk-1 was significantly reduced both at the transcriptional level (P < 0.04) and at the protein level (P < 0.007) in platelets isolated from the blood of patients with axial SpA.Our preliminary observations suggest that dysfunction of the megakaryocyte/platelet axis might be responsible for reduced serum Dkk-1 levels in patients with axial SpA. Dkk-1 is down-regulated in the platelets of patients with axial SpA, a mechanism that might play a role in new bone formation.
Supraventricular pacemaker underdrive in the absence of sinus nodal influences in the conscious dog.
Authors: J MLoeb, D KMurdock, W CRandall, D EEuler
Journal: Circulation Research (1979)

The ability to reduce and maintain heart rate by electrical stimulation (underdrive) was tested in three groups of chronically instrumented dogs: sinoatrial node intact, ectopic atrial pacemaker produced by injection of rapidly hardening latex into the sinoatrial nodal artery, and idioventricular pacemaker produced by injection of formalin into the atrioventricular node. In the conscious unsedated state, underdrive of sinoatrial or idioventricular pacemakers resulted in competition between driven and intrinsic foci. However, the cycle length of ectopic atrial pacemakers could be increased by 148.4 +/- 30.7 msec (P less than 0.001) and maintained at that value. Cessation of underdrive resulted in a period of pacemaker suppression similar to that produced following overdrive. Single premature stimuli produced marked cycle length prolongations in dogs with ectopic atrial foci. Total autonomic blockade had no significant effect on the production of underdrive. Thus, the results of the present experiments prov...
A new two-dimensional echocardiographic technique for evaluating right ventricular size and performance in patients with obstructive lung disease.
Authors: M RStarling, M HCrawford, S GSorensen, R AO'Rourke
Journal: Circulation (1982)

To compare two-dimensional (2-D) echocardiographic estimates of right ventricular size and performance to similar determinations from equilibrium radionuclide angiography (RNA) before and after isosorbide dinitrate, we evaluated 19 patients with severe chronic obstructive pulmonary disease. The end-diastolic and end-systolic volumes estimated from subcostal 2-D echocardiographic views of the right ventricle correlated with the RNA end-diastolic and end-systolic counts (r = 0.76 and 0.82, respectively). The 2-D echocardiographic and RNA right ventricular ejection fraction (EF) estimates also correlated (r = 0.80), and the average right ventricular EF measures of 42 +/- 11% and 40 +/- 12%, respectively, did not differ significantly. Nitrate administration produced a significant increase in heart rate (99 +/- 11 to 108 +/- 14 beats/min, p less than 0.001) and a decrease in systolic arterial pressure (139 +/- 23 to 120 +/- 22 mm Hg, p less than 0.001). Nitrates also significantly decreased the average 2-D ech...
RE: Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer
Authors: He Wen-zhuo, Xia Liang-ping
Journal: JNCI Journal of the National Cancer Institute (2015)

Colorectal cancer is a group of distinct diseases rather than a homogeneous one. Fotios Loupakis et al. (1) published an interesting paper, which suggested that patients with left-sided colorectal cancers had more favorable prognosis than right side. What’s more, the authors also proposed that the efficacy of bevacizumab was independent of tumor location. The study was based on well-known clinical trials and described in reasonable detail. In our opinion, there are three points that might weaken the stringency of their study.
Restenosis after placement of Palmaz-Schatz stents in native coronary arteries. Initial results of a multicenter experience.
Authors: S GEllis, MSavage, DFischman, D SBaim, MLeon, SGoldberg, J WHirshfeld, M WCleman, P STeirstein, CWalker
Journal: Circulation (1992)

BACKGROUNDSeveral metallic intracoronary stents are currently undergoing preliminary evaluation to ascertain potential benefit as means to reduce the 30-40% incidence of restenosis after balloon angioplasty.METHODS AND RESULTSTo determine the incidence and correlates of restenosis after placement of Palmaz-Schatz stents in native coronary arteries in the first group of patients selected for this procedure, clinical and quantitative angiographic data from 206 consecutive patients (221 stenoses) with successful stent placement (diameter stenosis < 50%) were analyzed. Six patients (2.9%) had thrombosis-mediated stent closure within 1 month after stent placement and were excluded from long-term angiographic follow-up. One hundred eighty-one (91%) of the remaining 200 patients had angiography at 5.8 +/- 2.1 months. Patients with and without follow-up did not differ in any baseline characteristic; in particular, history of restenosis at the site stented (73% versus 65%), placement of multiple overlapping stents...
Role of Na(+)-H+ exchange in mediating effects of endothelin-1 on normal and ischemic/reperfused hearts.
Authors: NKhandoudi, JHo, MKarmazyn
Journal: Circulation Research (1994)

Endothelin (ET) has been shown to be elevated under conditions of cardiac pathology and to produce diverse cardiac effects, including coronary constriction and a positive inotropic influence. We characterized the concentration- and time-dependent effects of the most potent of the ET isoforms, ET-1 (0.4, 2, and 4 nmol/L), on myocardial contractility and coronary resistance and assessed its effects on the ischemic and reperfused heart. Because ET-1 has been shown to activate the Na(+)-H+ exchanger in cardiac myocytes, we determined the contribution of the antiport by examining the effects of ET-1 in the presence of the Na(+)-H+ exchange inhibitor methylisobutyl amiloride (MIA). At all three concentrations, ET-1 produced an initial positive inotropic effect that was reversed with continued perfusion, the degree of the reversal being dependent on ET-1 concentration. With 0.4 nmol/L, contractility returned to pre-ET-1 values, whereas after 75 minutes of perfusion with 4 nmol/L ET-1, contractility was depressed...
Tone-dependent coronary arterial-venous pressure differences at the cessation of venous outflow during long diastoles.
Authors: SSatoh, F JKlocke, J MCanty
Journal: Circulation (1993)

BACKGROUNDThe origin and magnitude of the back pressure opposing diastolic coronary inflow remain controversial. The arterial pressure at which coronary inflow stops during a prolonged diastole, ie,   is higher than coronary venous pressure. However, because of capacitive discharge as distending pressure falls, flow at the microcirculatory level exceeds inflow, and coronary outflow ceases later than inflow. If coronary arterial pressure continues to exceed venous pressure at the point of venous flow cessation, zero-flow pressure cannot be an artifact of capacitive discharge.METHODS AND RESULTSCoronary inflow and outflow, arterial pressure, and right atrial pressure have been measured during long diastoles in closed-chest dogs chronically instrumented with volumetric flow probes on the great cardiac vein or coronary sinus as well as the circumflex artery. Although venous outflow continued for 1 to 4 seconds after arterial inflow ceased, coronary artery pressure at the point of venous fl...
Simultaneous recording of action potentials from endocardium and epicardium during ischemia in the isolated cat ventricle: relation of temporal electrophysiologic heterogeneities to arrhythmias.
Authors: SKimura, A LBassett, TKohya, P LKozlovskis, R JMyerburg
Journal: Circulation (1986)

We studied the effects of ischemia on transmembrane action potentials, conduction time, and refractory periods of both endocardial and epicardial muscle cells of coronary-perfused cat left ventricles. Oxygenated Tyrode's solution was perfused through the left anterior descending coronary artery, while the preparation was superfused with Tyrode's solution gassed with 95% N2 and 5% CO2. Transmembrane action potentials recorded simultaneously from endocardial and epicardial cells were normal during coronary perfusion. When perfusion was discontinued (ischemia), rapid deterioration of action potentials and prolongation of conduction time were observed in both endocardial and epicardial cells. The magnitude of the reduction of action potential amplitude and action potential duration (APD), and of prolongation of conduction time, was greater in epicardial cells than in endocardial cells, although the change in resting membrane potential was almost the same. However, APD of endocardial cells decreased progress...
Pertussis toxin-treated dog: a whole animal model of impaired inhibitory regulation of adenylate cyclase.
Authors: J WFleming, T DHodges, A MWatanabe
Journal: Circulation Research (1988)

We have shown previously that stimulation of high-affinity GTP hydrolysis and inhibition of adenylate cyclase activity by muscarinic agonists are mediated by pertussis toxin (IAP) substrates (Gi and Go) in canine cardiac sarcolemma. We have now used the pertussis toxin-treated dog as a whole animal model in which Gi- and Go-mediated biochemical mechanisms can be studied. Mongrel dogs were injected intravenously with IAP 48 hours prior to death and isolation of left ventricular sarcolemma. Treatment of the animal in vivo with the toxin prevented subsequent in vitro IAP-catalyzed [32P]ADP-ribosylation of substrates in cardiac, erythrocytic, and renal cortical plasma membranes, suggesting that ADP-ribosylation occurred in vivo from endogenous substrate. Consistent with our previous results obtained by treating sarcolemma in vitro with IAP, muscarinic receptor-mediated stimulation of high-affinity GTP hydrolysis and inhibition of GTP-activated adenylate cyclase activity were attenuated in sarcolemma purified ...
Fast computed tomography detection of coronary calcification in the diagnosis of coronary artery disease. Comparison with angiography in patients < 50 years old.
Authors: J AFallavollita, A SBrody, I LBunnell, KKumar, J MCanty
Journal: Circulation (1994)

BACKGROUNDThe predominant cause of coronary artery calcification is atherosclerosis. Although fast x-ray computed tomography (CT) has been demonstrated to be a sensitive technique to detect coronary calcification, the increasing prevalence of calcification with age has been associated with a low specificity for identifying obstructive atherosclerosis. We hypothesized that the specificity of this test would be improved in a younger patient population, making it more useful in the diagnosis of coronary artery disease.METHODS AND RESULTSWe compared fast CT-detected calcification with coronary angiography in 106 patients under the age of 50 years. Nonenhanced fast CT scans consisting of 20 contiguous 3-mm tomograms of the proximal coronary arteries were obtained during a single breath hold. A positive scan was defined as 4 contiguous voxels (> or = 1 mm2) of density > 130 Hounsfield units in the region of the epicardial coronary arteries. Calcification detected by fast CT had an 85% sensitivity to predict pat...
Loss of selective endothelial cell vasoactive functions caused by hypercholesterolemia in pig coronary arteries.
Authors: R ACohen, K MZitnay, C CHaudenschild, L DCunningham
Journal: Circulation Research (1988)

The influence of hypercholesterolemia on the reactivity of coronary arteries was investigated after feeding a high-cholesterol diet to pigs for 9 weeks. After this duration of hypercholesterolemia, the fatty or intimal proliferative changes of atherosclerosis were not yet evident in the coronary arteries by light or electron microscopy. Changes in isometric tension were compared in isolated ring segments of coronary arteries from normal and hypercholesterolemic animals. The endothelium failed to inhibit contractions caused by 5-hydroxytryptamine in coronary arteries from hypercholesterolemic animals, but it did so in normal vessels. In contracted arteries, endothelium-dependent relaxations caused by 5-hydroxytryptamine and substance P were reduced by hypercholesterolemia. In contrast, endothelium-dependent relaxations mediated by norepinephrine acting at alpha 2-adrenoceptors and those caused by the calcium ionophore A23187 were unaffected. Endothelium-independent beta-adrenergic relaxations caused by nor...
Left ventricular diastolic Doppler characteristics in beta-thalassemia major.
Authors: D TKremastinos, D PTsiapras, G ATsetsos, E IRentoukas, H PVretou, P KToutouzas
Journal: Circulation (1993)

BACKGROUNDDiastolic left ventricular function expressed by diastolic Doppler characteristics of the left ventricle has never been properly investigated.METHODS AND RESULTSLeft ventricular inflow and pulmonary vein flow patterns were assessed by Doppler echocardiography in 88 beta-thalassemia major patients with normal left ventricular systolic function; 34 were young (age, 15.1 +/- 3.2 years) and 54 were adults (age, 25.1 +/- 3.6 years). The findings were compared with those obtained from 22 young (age, 13.8 +/- 2.4 years) and 24 adult (age, 25.3 +/- 4.1 years) normal individuals. In both groups of patients, peak flow velocities in early (E) and late (A) diastole were higher than in the control subjects (young E: P < .01; adult E: P < .001; young A: P < .05; adult A: P < .05), whereas no difference was found in the E/A ratio, deceleration time, or isovolumic relaxation time. Pulmonary vein systolic (S) and diastolic (D) velocities were also higher in beta-thalassemia major patients compared with the contr...
Contractility in mammalian heart muscle; calcium and osmolality.
Authors: M AGoethals, S MAdèle, D LBrutsaert
Journal: Circulation Research (1975)

The influence of osmolality of the external medium on the calcium (Ca) dependency of contractility of isolated electrically excited cat papillary muscle was examined. Maximum unloaded velocity of shortening was directly measured by load clamping the muscle from the preload (at the length, Lmax, at which maximum active tension was developed) to zero load (zero load clamp). Peak velocity of shortening at the Lmax preload, peak total force, peak rate of force development, time to peak force, and time to half relaxation were also recorded. The performance-Ca response curves (Ca concentration between 1.25 nM and 10 nM) for maximum unloaded velocity of shortening, peak shortening velocity at Lmax preload, total force, and peak rate of force development were shifted to the left when osmolality was increased (from 290 mosmoles to 410 mosmoles) with sucrose, and to the right when osmolality was increased with NaCl. The sensitivity for Ca, as determined from the slopes of these response curves, appeared essentially...