tbuckley/cabot-search huggingface dataset:
Gene targeting. The precise manipulation of the mammalian genome.
Authors: JRobbins
Journal: Circulation Research (1993)

Genetics is a powerful tool for studying the function of different gene products as well as the physiological consequences of a normal or aberrant polypeptide. Until recently, the most powerful genetic applications have been restricted to relatively simple organisms whose genomes are more easily manipulated. For a number of years, in lower organisms, it has been possible to create defined genetic changes that are targeted to a specific locus or even to a defined codon or transcriptional regulatory sequence. With the development of gene targeting using embryonic stem cells derived from the preimplantation blastocyst of a mouse, it has become possible to extend these experiments to a mammalian system. Via homologous recombination, one can ablate, or knock out, a defined genetic locus or mutate a particular set of nucleotides that encodes a peptide domain of interest. These techniques, when applied to genes that underlie normal cardiovascular function, promise to define the exact role(s) different proteins...
Effect of external force on relaxation kinetics in single frog atrial cardiac cells.
Authors: MTarr, J WTrank, K KGoertz
Journal: Circulation Research (1983)

The effects of external force on relaxation kinetics were investigated in isolated single frog (Rana catesbeiana) atrial cells. We found that force decay occurred at a maximum and constant rate for a significant portion of auxotonic relaxation, and this rate was linearly related to the peak force developed during auxotonic contraction. The slope of the linear relationship between the maximum rate of auxotonic force decay and peak auxotonic force was not affected by changes in the level of contractile activation produced by activating the cell with different stimulus durations. The rate of force change during auxotonic contraction and relaxation in the isolated cell is directly related to the average sarcomere velocity within the cell. Thus, the results indicate that during auxotonic relaxation the velocity of sarcomere extension is directly related to the peak auxotonic force, and sarcomere extension, during relaxation, is therefore affected by external force. The direct effect of external force on relaxa...
Contractile reserve and left ventricular function in regional myocardial ischemia in the dog.
Authors: CYoran, E HSonnenblick, E SKirk
Journal: Circulation (1982)

Contractile activity remaining in a region made ischemic by acute occlusion of the left anterior descending coronary artery (LAD) was assessed in dogs relative to its role in maintaining left ventricular (LV) function. Compensatory increases in contractility of normal myocardium were eliminated by treating all dogs with reserpine (3 mg/kg) to deplete their catecholamine stores. LV function was determined by measuring stroke volume while increasing the LV filling pressure with a shunt from the aorta to left atrium. Heart rate and mean aortic pressure were kept constant. LV function was studied after occlusion of the LAD alone and after the selective infusion of potassium chloride (1 mEq/ml) into the LAD to raise the regional extracellular potassium concentration to 30 mEq/ml. The reduction in LV function induced by LAD ligation was less than the reduction caused by abolishing contraction in the entire zone supplied by the LAD with infusion of potassium. The totally cardioplegic zone induced by potassium am...
Correlation of platelet survival time with occlusion of saphenous vein aorto-coronary bypass grafts.
Authors: PSteele, DBattock, GPappas, EGenton
Journal: Circulation (1976)

Platelet survival time is frequently shortened in patients with coronary artery disease, and it is one of several factors that might contribute to graft occlusion after saphenous vein coronary artery bypass (CAB). In 35 patients with CAB, average platelet survival (autologous labeling with 51Chromium) was shortened in 20 with one or more saphenous vein grafts occluded and normal in 15 with all grafts open. Of 15 with all grafts open, individual levels of platelet survival were normal in 10 while in 20 with one or more grafts occluded platelet survival was normal in only one. Platelet survival was not altered by coronary surgery and nine of ten with shortened platelet survival pre-operatively had graft occlusion. Platelet survival did not correlate with either parent artery occlusion or serum lipoproteins. These findings suggest a relationship between shortened platelet survival and saphenous vein graft occlusion and suggest that platelet suppressant therapy might be useful in preventing graft occlusion.
A simplified, single-lead unipolar transvenous cardioversion-defibrillation system.
Authors: G HBardy, GJohnson, J EPoole, G LDolack, P JKudenchuk, DKelso, RMitchell, RMehra, BHofer
Journal: Circulation (1993)

BACKGROUNDTransvenous implantable cardioverter-defibrillators provide significant advantages in the treatment of patients with life-threatening ventricular arrhythmias. However, present technology requires considerable electrophysiology expertise, multiple incisions, and long operative times for successful implementation.METHODS AND RESULTSIn this study, we present a prototype of a new, easy-to-insert unipolar transvenous defibrillation system that has the reliability of epicardial defibrillation but the ease of pacemaker insertion. This system incorporates a single anodal right ventricular defibrillation electrode using a 65% tilt biphasic pulse delivered to a 108-cm2 surface area pulse generator titanium alloy shell as an active cathode placed in a left infraclavicular pocket. Testing of this system was performed before implantation of a standard nonthoracotomy-transvenous defibrillation system in 40 consecutive patients with a history of ventricular tachycardia or fibrillation. The simplified unipolar ...
Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle.
Authors: R PKelly, RTunin, D AKass
Journal: Circulation Research (1992)

This study tests the hypothesis that arterial vascular stiffening adversely influences in situ left ventricular contractile function and energetic efficiency. Ten reflex-blocked anesthetized dogs underwent a bypass operation in which a Dacron graft was sewn to the ascending aorta and connected to the infrarenal abdominal aorta via a plastic conduit. Flow was directed through either native aorta or plastic conduit by placement of vascular clamps. Arterial properties were measured from aortic pressure-flow data, and ventricular function was assessed by pressure-volume (PV) relations. Coronary sinus blood was drained via an extracorporeal circuit for direct measurement of myocardial O2 consumption (MVO2). Data at multiple steady-state preload volumes were combined to derive chamber function and energetics relations. Energetic efficiency was assessed by the inverse slope of the MVO2-PV area relation. Directing flow through plastic versus native aorta resulted in a 60-80% reduction in compliance but little cha...
Chronic Idiopathic Thrombocytopenic Purpura
Authors: Robert McMillan
Journal: New England Journal of Medicine (1981)

CHRONIC idiopathic (or immune) thrombocytopenic purpura (ITP) is a syndrome characterized by persistent thrombocytopenia caused by a circulating antiplatelet factor that results in platelet destruction by the reticuloendothelial system. It seems likely that the antiplatelet factor in most patients is an IgG antibody directed toward a platelet-associated antigen, although circulating immune complexes may have a role in some cases. This syndrome has been termed "autoimmune" by some authors, but this designation seems premature, since present evidence does not rule out a heterologous antigen as the causative agent. Characterization of the antigen (or antigens) will be necessary to establish true autoimmunity. . . .
"Consistent parallel relationships among myocardial oxygen consumption, coronary blood flow, and pericardial infusate adenosine concentration with various interventions and beta-blockade in the dog".
Authors: P Borgdorff, R Braakman, A C van Haelst, G A van Huis, J P de Jong, R Krams, G J Langewouters, P Sipkema, N Westerhof
Journal: Circulation Research (1984)
Does Personal Protective Equipment In The Era Of Covid-19 Influence Quality Of Colonoscopy?
Authors: C Nascimento, L Ramos, C Frias Gomes, J Revés, B Morão, C Palmela, A Ferreira, L Glória
Journal: Endoscopy (2021)

Aims In March 2020, COVID-19 has been declared as a pandemic, resulting in modulation of endoscopic activity and enhancement of personal protective equipment (PPE) when performing colonoscopy. Recently, it has been shown that such PPE interferes with visual and auditory perception. Our aim was to evaluate if PPE may negatively impact colonoscopy quality.
Prevention of childhood leukaemia by lifestyle changes
Authors: Christine J. Harrison
Journal: Leukemia (2021)

Greaves et al. pose the ambitious question: can childhood leukaemia be prevented?This research group has made significant contributions over the last decades in terms of understanding the processes of initiation and progression of childhood leukaemia, based largely on detailed investigations of certain subgroups of childhood acute lymphoblastic leukaemia (ALL) [2], thus they are in the strongest position to convince us of the possibility.Childhood ALL is one of the greatest success stories of modern medicine: as a result of improved patient management and risk-adapted administration of established drug regimens, more than 90% of children now survive the disease [3].Although astounding, the price paid for this achievement is prolonged and distressing therapies, with high levels of unpleasant side effects and lasting morbidities.Thus, prevention would provide an extremely welcome alternative.Before considering prevention, those underlying causes of ALL, which may respond to intervention, need to be identified.The most popular explanations suggest that childhood ALL arises from an abnormal immune response to common infections, attributed alternatively to population mixing [4] or, as proposed by Greaves et al., delayed infection.The latter is based on normal functional development of the immune system during the perinatal period by exposure to microbial infection.This in turn, influences the composition of the infant microbiome, impacting on the health of the child [2].Inadequate exposure to natural microbes distorts the immune system, which in infancy is predicted to dysregulate the response to common infections that could lead to ALL.
<i>Brassica rapa</i> Domestication: Untangling Wild and Feral Forms and Convergence of Crop Morphotypes
Authors: Alex C McAlvay, Aaron P Ragsdale, Makenzie E Mabry, Xinshuai Qi, Kevin A Bird, Pablo Velasco, Hong An, J Chris Pires, Eve Emshwiller
Journal: Molecular Biology and Evolution (2021)

The study of domestication contributes to our knowledge of evolution and crop genetic resources. Human selection has shaped wild Brassica rapa into diverse turnip, leafy, and oilseed crops. Despite its worldwide economic importance and potential as a model for understanding diversification under domestication, insights into the number of domestication events and initial crop(s) domesticated in B. rapa have been limited due to a lack of clarity about the wild or feral status of conspecific noncrop relatives. To address this gap and reconstruct the domestication history of B. rapa, we analyzed 68,468 genotyping-by-sequencing-derived single nucleotide polymorphisms for 416 samples in the largest diversity panel of domesticated and weedy B. rapa to date. To further understand the center of origin, we modeled the potential range of wild B. rapa during the mid-Holocene. Our analyses of genetic diversity across B. rapa morphotypes suggest that noncrop samples from the Caucasus, Siberia, and Italy may be truly wild, whereas those occurring in the Americas and much of Europe are feral. Clustering, tree-based analyses, and parameterized demographic inference further indicate that turnips were likely the first crop type domesticated, from which leafy types in East Asia and Europe were selected from distinct lineages. These findings clarify the domestication history and nature of wild crop genetic resources for B. rapa, which provides the first step toward investigating cases of possible parallel selection, the domestication and feralization syndrome, and novel germplasm for Brassica crop improvement.
Effect of extension of infarction on serial CK activity.
Authors: F RCobb, R GIrvin, R CHagerty, C CRoe
Journal: Circulation (1979)

The effects of extension of myocardial infarction by reduction of regional myocardial blood flow (RMBF) to an ischemic region on serum CK activity was examined in 14 awake dogs. Initial infarction was effected by occlusion of the distal left circumflex coronary artery (LCCA) and subsequent extension was produced by occlusion of the proximal LCCA 6, 12 or 18 hours after distal occlusion. Extension was verified by serial measurements of RMBF using radioisotope-labeled microspheres before and after proximal occlusion. Serum CK activity increased initially 2-4 hours after distal coronary occlusion and then increased rapidly and reached peak values 12 hours after occlusion. When the infarction was extended at 6, 12 or 18 hours after initial occlusion, CK appearance was immediately reduced in the 6- and 12-hour experiments, but not in the 18-hour experiments. Extension of infarction at each interval caused delayed increases in CK activity beginning 2-5 hours after proximal occlusion, with peak values occurring ...
The effects of delta-9-tetrahydrocannabinol (cannabis) on cardiac performance with and without beta blockade.
Authors: CKanakis, J MPouget, K MRosen
Journal: Circulation (1976)

Systolic time intervals (STI) were measured in ten healthy male volunteers before and after intravenous (i.v.) administration of 25 mug/kg delta-9-tetrahydrocannabinol (delta-9-THC). Mean +/- SEM heart rate increased 32 +/- 7 beats/min, while systolic and diastolic blood pressures were unchanged after delta-9-THC. Total electromechanical systole lengthened 17 +/- 4.2 msec, left ventricular ejection time (LVETc) prolonged 24 +/- 4.0 msec and pre-ejection period (PEP) shortened 17 +/- 5.1 msec after delta-9-THC. All of these changes were significant (P less than 0.01). In nine other subjects who underwent prior beta adrenergic blockade, similar but less marked changes were noted in heart rate, blood pressure, and STI after delta-9-THC. The shortening of PEP after delta-9-THC was only 9 msec (NS) in beta blocked subjects. Thus, delta-9-THC significantly increased heart rate, shortened PEP and prolonged LVETc without any change in afterload. Beta adrenergic blockade prevented significant shortening of PEP and...
Short-term effect of dynamic exercise on arterial blood pressure.
Authors: L SPescatello, A EFargo, C NLeach, H HScherzer
Journal: Circulation (1991)

BACKGROUNDTo quantify the duration of postexercise hypotension at different exercise intensities, we studied six unmedicated, mildly hypertensive men matched with six normotensive controls.METHODS AND RESULTSEach subject wore a 24-hour ambulatory blood pressure monitor at the same time of day for 13 consecutive hours on 3 different days. On each of the 3 days, subjects either cycled for 30 minutes at 40% or 70% maximum VO2 or performed activities of daily living. There was no intensity effect on the postexercise reduction in blood pressure, so blood pressure data were combined for the different exercise intensities. Postexercise diastolic blood pressure and mean arterial pressure were lower by 8 +/- 1 (p less than 0.001) and 7 +/- 1 mm Hg (p less than 0.05), respectively, than the preexercise values for 12.7 hours in the hypertensive group. These variables were not different before and after exercise in the normotensive group. Systolic blood pressure was reduced by 5 +/- 1 mm Hg (p less than 0.05) for 8.7...
Verapamil preserves myocardial performance and energy metabolism in left ventricular hypertrophy following ischemia and reperfusion. Phosphorus 31 magnetic resonance spectroscopy study.
Authors: P TBuser, SWagner, S TWu, NDerugin, W WParmley, C BHiggins, JWikman-Coffelt
Journal: Circulation (1989)

While calcium entry blockers have a beneficial influence on the postischemic recovery of the nonhypertrophied heart, their influence on the hypertrophied heart has not been determined. The aim of this study was to assess postischemic recovery of myocardial performance and energy metabolites in rat hearts with left ventricular hypertrophy pretreated either chronically or acutely with verapamil. Left ventricular hypertrophy was induced by suprarenal constriction of the abdominal aorta. Hemodynamics and phosphorus 31 magnetic resonance spectra were monitored simultaneously in the isolated hearts during control perfusion, after 30 minutes of global ischemia, and after 30 minutes of reperfusion. All hypertrophied hearts had significantly higher rate-pressure products than normal hearts. Compared with normal hearts, oxygen consumption was significantly lower in all hypertrophied hearts, especially untreated hypertrophied hearts. Also, before ischemia all normal or hypertrophied hearts (treated or untreated) beg...
Postinfarction ventricular septal rupture: the importance of location of infarction and right ventricular function in determining survival.
Authors: C AMoore, T WNygaard, D LKaiser, A ACooper, R SGibson
Journal: Circulation (1986)

Over a 5.5 year period, 1264 consecutive patients with acute myocardial infarction as confirmed by enzyme levels were prospectively identified. Of these, 25 (2%) suffered ventricular septal rupture (pulmonary/systemic flow range 1.5 to 6) 7 +/- 7 days after onset of myocardial infarction. Death occurred in 14 patients (56%) and was more common after inferior than anterior myocardial infarction (11 of 15 [73%] vs three of 10 [30%], p less than .05). Among 133 variables analyzed, survivors and nonsurvivors were similar with respect to all premorbid clinical characteristics, infarct size as assessed by peak creatine kinase values, shunt size, two-dimensional echocardiographic and hemodynamic indexes of left ventricular function, and extent of coronary disease. Compared with survivors, the nonsurvivors had greater impairment of right ventricular function as determined by a higher two-dimensional echocardiographically derived right ventricular wall motion index (RVWMI) (0.55 +/- 0.87 vs 1.70 +/- 0.45, p less t...
Effects of pacing-induced ischemia on early left ventricular filling and regional myocardial dynamics and their modification by nifedipine.
Authors: YNakamura, SSasayama, HNonogi, SMiyazaki, MFujita, YKihara, TKonishi, CKawai
Journal: Circulation (1987)

The effect of pacing-induced ischemia on early left ventricular filling and regional myocardial lengthening was studied in 11 patients with coronary artery disease (CAD) and six control patients with normal coronary arteriograms. All of the 11 patients with CAD developed typical anginal pain during pacing tachycardia, and in the postpacing beat, the left ventricular end-diastolic pressure (LVEDP) rose from 13 +/- 4 to 26 +/- 4 mm Hg (mean +/- SD, p less than .01), the relaxation time constant increased from 43 +/- 9 to 59 +/- 7 msec (p less than .01), and the ejection fraction diminished from 62.1 +/- 6.7 to 51.6 +/- 10.6% (p less than .01). However, the peak rate of early left ventricular filling (LVPF) obtained from frame-by-frame analysis of left ventriculograms and the LVPF normalized for the stroke volume and for the end-diastolic volume did not change significantly. In the ischemic segment, the peak rate of lengthening (PL) decreased by 45% with ischemia, and the PL normalized for the end-diastolic ...
The circulatory influences of vagal afferents at rest and during coronary occlusion in conscious dogs.
Authors: V SBishop, D FPeterson
Journal: Circulation Research (1978)

We studied the role of cardiopulmonary vagal afferents in the cardiovascular responses to coronary artery occlusion in conscious dogs with intact carotid sinuses and following functional denervation of the arterial baroreceptors. The contributions of vagal afferents were determined by cold blocking the vagi. In dogs with intact carotid sinuses, coronary artery occlusion produced small decreases in mean cardiac output and arterial pressure, whereas heart rate increased by 35 beats/min. In dogs with intact carotid sinuses, vagal cold block increased mean arterial pressure by 22 +/- 2 (mean +/- SE) mm Hg and heart rate by 90 +/- 6 beats/min. Mean cardiac output increased by 505 +/- 90 ml/min. With the exception of heart rate, responses to coronary occlusion during vagal cold block were similar to the occlusion response prior to vagal cold block. Furthermore, prior occlusion of the coronary artery did not significantly influence the responses to vagal cold block. After arterial baroreceptor denervation, coron...
CAR-T cell therapy: current limitations and potential strategies
Authors: Robert C. Sterner, Rosalie M. Sterner
Journal: Blood Cancer Journal (2021)

Abstract Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
Color Doppler regurgitant characteristics of normal mechanical mitral valve prostheses in vitro.
Authors: HBaumgartner, SKhan, MDeRobertis, LCzer, GMaurer
Journal: Circulation (1992)

BACKGROUNDTo evaluate normal regurgitant characteristics of St. Jude (SJ) and Medtronic-Hall (MH) mitral valves, four sizes (25-31 mm) of each were studied in a pulsatile flow model.METHODS AND RESULTSRegurgitant flow was measured by flowmeter at left ventricular pressures of 80, 130, and 180 mm Hg. Peak regurgitant flow rates ranged from 6.2 to 12.7 cm3/sec in SJ valves and from 7.9 to 17.5 cm3/sec in MH valves. Regurgitant orifice areas calculated from the Doppler continuity equation ranged from 1.6 to 2.0 mm2 in SJ valves and from 2.2 to 2.9 mm2 in MH valves. Regurgitant volumes across the closed valve at a left ventricular pressure of 130 mm Hg were normalized to an ejection time of 280 msec and ranged from 1.5 to 1.9 cm3 in SJ valves and from 2.1 to 2.8 cm3 in MH valves. Jets were imaged by color Doppler in six rotational planes, and jet size and morphology were compared with those of regurgitant jets from circular orifices with sizes comparable to the calculated prosthetic valve regurgitant orifices...