tbuckley/cabot-search huggingface dataset:
Regional changes in intracellular potassium and sodium activity after healing of experimental myocardial infarction in cats.
Authors: SKimura, A LBassett, M SGaide, P LKozlovskis, R JMyerburg
Journal: Circulation Research (1986)

After healing of experimental myocardial infarction in cat hearts, endocardial cells demonstrate persistent regional electrical changes. These include long action potential duration in surviving cells over the infarct scar, and short action potential duration and low membrane potential in border zone cells between the scar and normal tissue. We studied the basis for these electrophysiological changes by measuring intracellular potassium and sodium activity with ion-sensitive microelectrodes in normal, border, and infarct zone cells of the cat left ventricle 2-6 months after ligation of multiple distal tributaries of the left anterior descending and circumflex coronary arteries. In normal zone cells, intracellular potassium activity was 89.6 +/- 12.3 mM (mean +/- SD, n = 9), and sodium activity was 10.8 +/- 2.2 mM (n = 5). Neither was significantly different from infarct zone cells (91.2 +/- 15.0 and 10.5 +/- 3.0 mM, respectively). In contrast, border zone cells had significantly reduced intracellular pota...
Direct neurohumoral evidence for isolated sympathetic nervous system activation to skeletal muscle in response to cardiopulmonary baroreceptor unloading.
Authors: R GBaily, S AProphet, J SShenberger, RZelis, L ISinoway
Journal: Circulation Research (1990)

It has been postulated that cardiopulmonary baroreceptor unloading in humans results in nonuniform activation of the sympathetic nervous system. We reasoned that simultaneous measurements of arterial and venous norepinephrine (NE) spillover and clearance (using NE kinetics), muscle sympathetic neural activity (using microneurography), forearm blood flow (using plethysmography), and skin blood flow (using laser Doppler velocimetry) during lower body negative pressure at -15 mm Hg would isolate the location and extent of cardiopulmonary baroreceptor-mediated sympathetic nervous system activation. We exposed normal subjects (n = 8) to lower body negative pressure for 30 minutes, with measurements obtained at baseline, 5-10 minutes (EARLY), and 25-30 minutes (LATE). We found that arterial NE spillover, reflecting systemic sympathetic nervous system activation, did not increase significantly, whereas arterial NE clearance decreased significantly. In contrast, forearm venous NE spillover, reflecting skin and mu...
Biphasic contractions induced by milrinone at low temperature in ferret ventricular muscle: role of the sarcoplasmic reticulum and transmembrane calcium influx.
Authors: C OMalecot, D MBers, B GKatzung
Journal: Circulation Research (1986)

The effects of milrinone were studied in ferret papillary muscle stimulated at various rates and temperatures from 23 degrees to 36 degrees C. In voltage-clamp experiments, 50 micrograms/ml (0.237 mM) milrinone induced a 2.1-fold increase in calcium current at 28 degrees or 36 degrees C. At 50 micrograms/ml, milrinone transiently increased contractility in all muscles at 28 degrees C, but its steady-state effect was either increased (+50%) or decreased (-24.7%) steady-state twitch amplitude. A negative inotropic effect always occurred below 27 degrees C. Milrinone decreased the total twitch duration and split the twitch into two components (P1 and P2) in the absence of any evidence of aberrant conduction. Increasing milrinone concentration from 50 to 300 micrograms/ml decreased P1 and increased P2. Ryanodine (100 mM) or caffeine (10 mM) suppressed P1. Contractions elicited after 30 seconds of rest were also biphasic in the presence of milrinone, but not in its absence. P2 of post-rest contraction was incr...
Vestiges of the Bacterial Signal Recognition Particle-Based Protein Targeting in Mitochondria
Authors: Jan Pyrih, Tomáš Pánek, Ignacio Miguel Durante, Vendula Rašková, Kristýna Cimrhanzlová, Eva Kriegová, Anastasios D Tsaousis, Marek Eliáš, Julius Lukeš
Journal: Molecular Biology and Evolution (2021)

The main bacterial pathway for inserting proteins into the plasma membrane relies on the signal recognition particle (SRP), composed of the Ffh protein and an associated RNA component, and the SRP-docking protein FtsY. Eukaryotes use an equivalent system of archaeal origin to deliver proteins into the endoplasmic reticulum, whereas a bacteria-derived SRP and FtsY function in the plastid. Here we report on the presence of homologs of the bacterial Ffh and FtsY proteins in various unrelated plastid-lacking unicellular eukaryotes, namely Heterolobosea, Alveida, Goniomonas, and Hemimastigophora. The monophyly of novel eukaryotic Ffh and FtsY groups, predicted mitochondrial localization experimentally confirmed for Naegleria gruberi, and a strong alphaproteobacterial affinity of the Ffh group, collectively suggest that they constitute parts of an ancestral mitochondrial signal peptide-based protein-targeting system inherited from the last eukaryotic common ancestor, but lost from the majority of extant eukaryotes. The ability of putative signal peptides, predicted in a subset of mitochondrial-encoded N. gruberi proteins, to target a reporter fluorescent protein into the endoplasmic reticulum of Trypanosoma brucei, likely through their interaction with the cytosolic SRP, provided further support for this notion. We also illustrate that known mitochondrial ribosome-interacting proteins implicated in membrane protein targeting in opisthokonts (Mba1, Mdm38, and Mrx15) are broadly conserved in eukaryotes and nonredundant with the mitochondrial SRP system. Finally, we identified a novel mitochondrial protein (MAP67) present in diverse eukaryotes and related to the signal peptide-binding domain of Ffh, which may well be a hitherto unrecognized component of the mitochondrial membrane protein-targeting machinery.
Sympathetic neural modulation of cardiac impulse initiation and repolarization in the newborn rat.
Authors: GMalfatto, T SRosen, S FSteinberg, P CUrsell, L SSun, SDaniel, PDanilo, M RRosen
Journal: Circulation Research (1990)

We injected neonatal rats with nerve growth factor, the antiserum to nerve growth factor, or placebo for the first 10 days of life. Our goal was to determine the relation between sympathetic innervation of the developing heart, the electrocardiographic expression of cardiac rhythm, and the response of the heart to alpha-adrenergic stimulation with phenylephrine. We were especially interested in the latter area because of the prior demonstration in isolated cell systems of sympathetic neural modulation of a 41-kDa GTP regulatory protein and alpha-adrenergic responsiveness. Ten- to 11-day-old rats treated with nerve growth factor had more complete sympathetic innervation, faster heart rates, and higher levels of the 41-kDa protein than the placebo group. Electrophysiological studies were performed on isolated ventricular septa superfused with Tyrode's solution at 37.0 degrees-37.5 degrees C. The electrophysiological response of septa to 10(-9) and 10(-8) M phenylephrine from the 10-11-day-old nerve growth f...
Electrophysiological responses of cardiac muscle to isoproterenol covalently linked to glass beads.
Authors: EBecker, W RIngebretsen, S EMayer
Journal: Circulation Research (1977)

We investigated the effects of isoproterenol aryl glass beads on the electrical properties of cardiac muscle and related these to our previous results concerning biochemical and contractile effects (Ingebretsen et al., Circ, Rs., 40: 474-484, 1977). Beads (10-15) were placed near one end to guinea pig papillary muscles mounted horizontally in a bath perfused with Krebs-Henseleit solution at 30 degrees C and stimulated at 0.2 Hz. The beads produced increased tension and elevation and slight lengthening of the plateau potential when [k+]o = 3.8 mM. After depolarization to a resting potential of -49 mV with [K+]o = 22 mM, isoproterenol beads restored contraction to a comparable extent as occurred with 10(-8) M soluble drug. During field stimulation, action potentials were initiated at the site of bead application and spread decrementally. When beads were placed distal to the site of point stimulation, virtually no excitation could be obtained from cells in the vicinity of the beads. When they were placed clo...
In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.
Authors: J MGerrard, STaback, SSinghroy, J CDocherty, IKostolansky, AMcNicol, N LKobrinsky, J KMcKenzie, RRowe
Journal: Circulation (1989)

The effects of smoking, aspirin ingestion, and sex differences on bleeding times and bleeding time thromboxane B2 and 6-keto-prostaglandin (PG)F1 alpha production were examined. Nonsmoking men produced more thromboxane B2 (3.99 +/- 0.76 ng/ml) than nonsmoking women (2.13 +/- 0.24 ng/ml). Female smokers produced more thromboxane B2 (5.01 +/- 0.97 ng/ml) than nonsmoking women. Twenty-four hours after a single dose of 600 mg aspirin, in vitro production of thromboxane B2 in response to collagen fell by 95%, whereas in vivo production of thromboxane B2 and 6-keto-PGF1 alpha in bleeding time blood fell by 87% and 66%, respectively. Subjects with the lowest absolute levels of thromboxane B2 24 hours after aspirin were also those with the longest postaspirin bleeding times. Recovery of 6-keto-PGF1 alpha production was faster than recovery of thromboxane B2 production, but 6-keto-PGF1 alpha production for most subjects was still below basal 72 hours after aspirin. The influence of two different doses of long-term...
Second Allogeneic Hematopoietic Stem Cell Transplantation for Post-Transplant Relapsed Acute Leukemia in Children - an EBMT PDWP Retrospective Study
Authors: Isaac Yaniv, Aviva C. Krauss, Eric Beohou, Arnaud Dalissier, Selim Corbacioglu, Marco Zecca, Boris V Afanasyev, Massimo Berger, Miguel Angel Diaz, Krzysztof Kalwak, Petr Sedlacek, Stefania Varotto, Christina Peters, Peter Bader
Journal: Blood (2017)
Effect of exogenous angiotensin II on renal hemodynamics in the awake rat. Measurement of afferent arteriolar diameter by the microsphere method.
Authors: C HHsu, T WKurtz, J MSlavicek
Journal: Circulation Research (1980)

We measured cardiac output (CO), renal blood flow (RBF), renal plasma flow (RPF), and afferent arteriolar diameter by the microsphere method, and inulin clearance (GFR) simultaneously in awake rats given an infusion of exogenous angiotensin II (100 ng/min per kg). Angiotensin II did not affect the CO, whereas both RBF and RPF decreased significantly in rats infused with angiotensin II (RBF, 2.88 +/- 0.11, mean +/- SE; RPF, 1.78 +/- 0.09, n = 6) when compared to control animals given saline (RBF, 4.58 +/- 0.31; RPF, 2.80 +/- 0.24 ml/min per 100 g, n = 6, both P less than 0.005, respectively). Both mean arterial pressure (MAP) and renal vascular resistance (RVR) were significantly higher in rats infused with antiogensin II than in controls. The decrease in GFR did not parallel the reduction of RPF in rats infused with angiotensin II as reflected by their higher values of mean filtration fraction (41.1 +/- 1.6%, n = 6) than that of controls (33.7 +/- 2.4%, n = 6, P less than 0.05). Despite significant elevat...
Re: Adjuvant Treatment of High-Risk, Radically Resected Gastric Cancer Patients with 5-Fluorouracil, Leucovorin, Cisplatin, and Epidoxorubicin in a Randomized Controlled Trial
Authors: N. Fazio, R. Biffi, G. Curigliano, K. Lorizzo, M. G. Zampino, F. de Braud, A. Chiappa, A. Roth, A. Goldhirsch
Journal: JNCI Journal of the National Cancer Institute (2007)
Effects of long-term treatment with amiodarone on exercise hemodynamics and left ventricular relaxation in patients with hypertrophic cardiomyopathy.
Authors: W JPaulus, PNellens, G RHeyndrickx, EAndries
Journal: Circulation (1986)

The influence of long-term treatment with amiodarone on exercise hemodynamics and on left ventricular relaxation was studied prospectively in patients with hypertrophic cardiomyopathy. Rest-exercise hemodynamics (n = 9) and echocardiographic relaxation indexes (isovolumic relaxation time, dPW/dt) (n = 11) were measured in control conditions and after 5 weeks of oral amiodarone treatment (600 mg daily first week, 400 mg daily second week, 200 mg daily afterwards). Long-term amiodarone treatment in patients at rest caused a significant drop in heart rate from 80 +/- 11 to 75 +/- 11 beats/min (p less than .05), a rise in mean pulmonary artery pressure from 19 +/- 7 to 25 +/- 10 mm Hg (p less than .02), and a rise in mean pulmonary capillary wedge pressure from 11 +/- 4 to 17 +/- 8 mm Hg (p less than .05). Systemic arterial pressure, cardiac output, and systemic vascular resistance remained unaltered. Exercise tolerance assessed by serial supine bicycle stress testing was reduced in six of nine patients. Amio...
Exposure to fatty acid increases human low density lipoprotein transfer across cultured endothelial monolayers.
Authors: BHennig, D MShasby, A ASpector
Journal: Circulation Research (1985)

Human low density lipoproteins radiolabeled with 125I transfer across confluent monolayers of cultured porcine pulmonary artery endothelial cells. The amount transferred was dependent on the low density lipoprotein concentration and was not saturable at concentrations up to 300 micrograms protein per 0.5 ml medium. Gel filtration showed that more than 90% of the 125I which crossed the endothelial monolayer remained associated with low density lipoproteins, indicating that appreciable amounts of lipoprotein were not degraded during the transfer process. When the endothelial monolayer was exposed for 24 hours to culture media supplemented with 100-300 microM fatty acid complexed with 100 microM albumin, the amount of low density lipoprotein subsequently transferred increased by 65% to 150%. The extent of the increase was dependent on the type of fatty acid added and its concentration. At 200 microM, albumin-bound oleic and linoleic acids increased low density lipoprotein transfer, whereas palmitic, linoleni...
Myeloid Cell–associated Resistance to PD-1/PD-L1 Blockade in Urothelial Cancer Revealed Through Bulk and Single-cell RNA Sequencing
Authors: Li Wang, John P. Sfakianos, Kristin G. Beaumont, Guray Akturk, Amir Horowitz, Robert P. Sebra, Adam M. Farkas, Sacha Gnjatic, Austin Hake, Sudeh Izadmehr, Peter Wiklund, William K. Oh, Peter M. Szabo, Megan Wind-Rotolo, Keziban Unsal-Kacmaz, Xin Yao, Eric Schadt, Padmanee Sharma, Nina Bhardwaj, Jun Zhu, Matthew D. Galsky
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To define dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer. Experimental Design: We pursued an unbiased approach using bulk RNA sequencing data from two clinical trials to discover (IMvigor 210) and validate (CheckMate 275) pretreatment molecular features associated with resistance to PD-1/PD-L1 blockade in metastatic urothelial cancer. We then generated single-cell RNA sequencing (scRNA-seq) data from muscle-invasive bladder cancer specimens to dissect the cellular composition underlying the identified gene signatures. Results: We identified an adaptive immune response gene signature associated with response and a protumorigenic inflammation gene signature associated with resistance to PD-1/PD-L1 blockade. The adaptive immune response:protumorigenic inflammation signature expression ratio, coined the 2IR score, best correlated with clinical outcomes, and was externally validated. Mapping these bulk gene signatures onto scRNA-seq data uncovered their underlying cellular diversity, with prominent expression of the protumorigenic inflammation signature by myeloid phagocytic cells. However, heterogeneity in expression of adaptive immune and protumorigenic inflammation genes was observed among single myeloid phagocytic cells, quantified as the myeloid single cell immune:protumorigenic inflammation ratio (Msc2IR) score. Single myeloid phagocytic cells with low Msc2IR scores demonstrated upregulation of proinflammatory cytokines/chemokines and downregulation of antigen presentation genes, were unrelated to M1 versus M2 polarization, and were enriched in pretreatment blood samples from patients with PD-L1 blockade–resistant metastatic urothelial cancer. Conclusions: The balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood. See related commentary by Drake, p. 4139
Effect of stellectomy and vagotomy on ventricular refractoriness in dogs.
Authors: P JSchwartz, R LVerrier, BLown
Journal: Circulation Research (1977)

The influence of tonic sympathetic and parasympathetic nervous system activity on ventricular refractory period duration was studied in 13 mongrel dogs. Strength-interval curves were obtained from the apex of the right ventricular endocardium with a transvenous bipolar catheter. The effects of sympathetic activity were assessed by unilateral and bilateral stellectomies and tonic vagal effects were studied by inducing cholinergic blockade with atropine (0.2 mg/kg) and by sectioning the cervical vagi bilaterally. Right stellectomy shifted the strength-interval curve 3-5 msec earlier (P less than 0.005). In contrast, left stellectomy shifted the strength-interval curve 4-7 msec later (P less than 0.001). Thus, right and left unilateral stellectomy produced opposite effects. However, when the contralateral ganglion was removed, right and left stellectomy produced qualitatively similar effects, increasing refractoriness. The net effect of bilateral stellectomy was to shift the strength-interval curve 8-10 msec...
Prediction of outcome after mitral valve replacement in patients with symptomatic chronic mitral regurgitation. The importance of left atrial size.
Authors: DReed, R DAbbott, M LSmucker, SKaul
Journal: Circulation (1991)

BACKGROUNDThe ability to predict outcome after mitral valve replacement remains limited in patients with symptomatic chronic mitral regurgitation. The aims of this study were to determine the preoperative predictors of postoperative cardiac-related mortality and to assess the additive prognostic value of tests performed in such patients.METHODS AND RESULTSAccordingly, 176 patients (mean age, 57 +/- 14 years) who underwent mitral valve replacement were followed up for 3.8 +/- 0.5 years. Four categories of variables were analyzed to predict postoperative cardiac-related mortality: clinical, laboratory, two-dimensional echocardiographic (2DE), and cardiac catheterization. There were 39 cardiac-related deaths (29 due to congestive heart failure and 10 sudden). When the four categories were analyzed separately, two clinical, one laboratory, two 2DE, and one catheterization variable best predicted postoperative death. When these six variables were examined simultaneously, only three (one clinical and two 2DE) r...
Effects of intense antecedent sympathetic stimulation on sympathetic neurotransmission in the heart.
Authors: TYang, M NLevy
Journal: Circulation Research (1993)

We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as  stimulations) are known to release neuropeptide Y as well as norepinephrine. The changes in cardiac cycle length evoked by vagal and sympathetic test stimulations were progressively more attenuated as we increased the frequency and duration of the antecedent sympathetic release stimulations. We found that 2.5 minutes after a maximal release stimulation (30 Hz for 5 minutes), the mean +/- SEM chronotropic responses to the vagal and sympathetic test stimulations were diminished to 36.5 +/- 1.6% and 54.7 +/- 1.3% respectively, of the prestimulation responses. The mean times for the chronotropic responses to the vagal and sympathetic test stimulations to recover to their control values were 52.0 +/- 1.3 and 63.2 +/- 2.9 minutes, respec...
The mechanism of transluminal angioplasty: evidence for formation of aneurysms in experimental atherosclerosis.
Authors: T ASanborn, D PFaxon, CHaudenschild, S BGottsman, T JRyan
Journal: Circulation (1983)

Quantitative histologic examination (morphometric analysis) of pressure-perfused rabbit atherosclerotic arteries was used to determine whether compression of atheromatous material occurs with transluminal angioplasty. Experimental atherosclerosis was developed in both iliac arteries, with transluminal angioplasty performed on the left iliac while the right iliac served as a nondilated control. Angiography showed equal degrees of luminal narrowing before angioplasty (p = NS). Angioplasty reduced the left iliac narrowing in all animals studied. Morphometric analysis of histologic sections of the left and right iliac arteries disclosed significant differences in luminal and total vessel areas (p less than .05), whereas arterial wall (intima and media) areas were similar (p = NS). Dilated areas often demonstrated marked intimal splitting with dissection into the media. At higher magnification, loss of nuclear staining and dense layers of extracellular matrix consistent with stretching were frequently seen. It...
Contingent Fees and Malpractice
Authors: R.K.Y. Dusinberre
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The LETTER to the Editor from a lawyer on "Contingent Fees and Malpractice" (<b>219</b>:756,1972) demonstrates again the impossibility of coping with legal thinking. Counselor can think of "no better" deterrent to the initiation of "meritless" claims than the contingent fee, when and if it obligates the lawyer to pay for his own and, in his illustration, other expenses. How does he know his case is "meritless" until he has gambled and lost? As Will Rogers said, "The way to make money is to buy only stocks that go up. If they don't go up, don't buy them." He recommends contingent fees for doctors. He fails to mention that even when the patient survives the surgical risk, the doctor may not get paid. His ethic requires separation of medical and financial risks. Not so the lawyer, who gets his fee before the client. Medicine can guarantee only
Ampullary Radiofrequency Ablation For The Treatment Of Residual And Recurrence Neoplasia After Endoscopic Papillectomy: Report Of A Tertiary Center
Authors: Y Dahel, M Giovannini, C Pesenti, JP Ratone, S Hoibian, F Caillol
Journal: Endoscopy (2021)

Aims Endoscopic papillectomy is the recommended treatment for adenoma, CIS and intramucosal adenocarcinoma of ampulla but incomplete margin and recurrence are common. Radiofrequency ablation (RFA) as a complementary treatment of papillectomy margin is an emerging technique. The goal of this study was to evaluate retrospectively feasibility and efficiency of this technique in our center.
Tracking of blood lipids and blood pressures in school age children: the Muscatine study.
Authors: W RClarke, H GSchrott, P ELeaverton, W EConnor, R MLauer
Journal: Circulation (1978)

In four cross sectional school screens, the Muscatine Study has sampled 8,909 school children; 820 have been studied repeatedly over a six-year period. Tracking of measurements described by the relationship between repeated observations and the relationship between peer rank orderings over the six-year period has been studied. For height and weight, correlations between observations six years apart were approximately 0.74 and about 60% of children initially in the upper quintile were there again six years later. Six-year correlations were 0.65 for skinfold and 0.61 for cholesterol. Four-year correlation for fasting triglyceride was 0.40. Six-year correlations were 0.30 for casual systolic blood pressure and 0.18 for diastolic blood pressure. Peer rank orderings for both blood pressures were highly variable. Height and weight track well, and thus routine measurement of these variables are useful in identifying children with growth perturbing disorders. Cholesterol and, to a lesser degree, triglycerides als...