tbuckley/cabot-search huggingface dataset:
Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma
Authors: Jennifer A. Foltz, Brian T. Hess, Veronika Bachanova, Nancy L. Bartlett, Melissa M. Berrien-Elliott, Ethan McClain, Michelle Becker-Hapak, Mark Foster, Timothy Schappe, Brad Kahl, Neha Mehta-Shah, Amanda F. Cashen, Nancy D. Marin, Kristen McDaniels, Chaz Moreno, Matthew Mosior, Feng Gao, Obi L. Griffith, Malachi Griffith, Julia A. Wagner, Narendranath Epperla, Amy D. Rock, John Lee, Allegra A. Petti, Patrick Soon-Shiong, Todd A. Fehniger
Journal: Clinical Cancer Research (2021)

N-803 is an IL15 receptor superagonist complex, designed to optimize in vivo persistence and trans-presentation, thereby activating and expanding natural killer (NK) cells and CD8+ T cells. Monoclonal antibodies (mAbs) direct Fc receptor-bearing immune cells, including NK cells, to recognize and eliminate cancer targets. The ability of IL15R agonists to enhance tumor-targeting mAbs in patients has not been reported previously.Relapsed/refractory patients with indolent non-Hodgkin lymphoma were treated with rituximab and intravenous or subcutaneous N-803 on an open-label, dose-escalation phase I study using a 3+3 design (NCT02384954). Primary endpoint was maximum tolerated dose. Immune correlates were performed using multidimensional analysis via mass cytometry and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) which simultaneously measures protein and single-cell RNA expression.This immunotherapy combination was safe and well tolerated and resulted in durable clinical responses including in rituximab-refractory patients. Subcutaneous N-803 plus rituximab induced sustained proliferation, expansion, and activation of peripheral blood NK cells and CD8 T cells, with increased NK cell and T cells present 8 weeks following last N-803 treatment. CITE-seq revealed a therapy-altered NK cell molecular program, including enhancement of AP-1 transcription factor. Furthermore, the monocyte transcriptional program was remodeled with enhanced MHC expression and antigen-presentation genes.N-803 combines with mAbs to enhance tumor targeting in patients, and warrants further investigation in combination with immunotherapies.
Effects of ryanodine and caffeine on contractility, membrane voltage, and calcium exchange in cultured heart cells.
Authors: C ARasmussen, J LSutko, W HBarry
Journal: Circulation Research (1987)

To investigate the mechanisms of action of ryanodine and caffeine, changes in mechanical and electrical activity caused by these agents were correlated with alterations in 45Ca fluxes and cell Ca contents in chick embryo ventricular cell monolayer cultures. Ryanodine (10(-10)-10(-5) M) irreversibly decreased contraction amplitude by 10-70% relative to control in a concentration-dependent manner with minimal effects on electrical activity. Ryanodine caused a slight decrease in rapid 45Ca uptake, but no change in total exchangeable calcium content or rapid 45Ca efflux. Caffeine (1-20 mM) caused a transient (less than 10 seconds) 5-12% increase in contraction amplitude followed by a sustained 9-76% decrease in contraction amplitude and a 10 mV decrease in diastolic membrane voltage. Caffeine caused a decrease in rapid 45Ca uptake, a decrease in total exchangeable calcium content, and an increase in rapid 45Ca efflux. These results suggest that caffeine produces a decrease in sarcoplasmic reticulum (SR) Ca2+ ...
Migration through a Major Andean Ecogeographic Disruption as a Driver of Genetic and Phenotypic Diversity in a Wild Tomato Species
Authors: Jacob B Landis, Christopher M Miller, Amanda K Broz, Alexandra A Bennett, Noelia Carrasquilla-Garcia, Douglas R Cook, Robert L Last, Patricia A Bedinger, Gaurav D Moghe
Journal: Molecular Biology and Evolution (2021)

Evolutionary dynamics at the population level play a central role in creating the diversity of life on our planet. In this study, we sought to understand the origins of such population-level variation in mating systems and defensive acylsugar chemistry in Solanum habrochaites-a wild tomato species found in diverse Andean habitats in Ecuador and Peru. Using Restriction-site-Associated-DNA-Sequencing (RAD-seq) of 50 S. habrochaites accessions, we identified eight population clusters generated via isolation and hybridization dynamics of 4-6 ancestral populations. Detailed characterization of mating systems of these clusters revealed emergence of multiple self-compatible (SC) groups from progenitor self-incompatible populations in the northern part of the species range. Emergence of these SC groups was also associated with fixation of deleterious alleles inactivating acylsugar acetylation. The Amotape-Huancabamba Zone-a geographical landmark in the Andes with high endemism and isolated microhabitats-was identified as a major driver of differentiation in the northern species range, whereas large geographical distances contributed to population structure and evolution of a novel SC group in the central and southern parts of the range, where the species was also inferred to have originated. Findings presented here highlight the role of the diverse ecogeography of Peru and Ecuador in generating population differentiation, and enhance our understanding of the microevolutionary processes that create biological diversity.
Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments.
Authors: FBennardini, AWrzosek, MChiesi
Journal: Circulation Research (1992)

alpha B-Crystallin is a 20-kd peptide highly homologous to the small heat-shock proteins. This protein forms soluble homomultimeric complexes (M(r), 300-700 kd) and is very abundant in cardiac muscle cells. In vitro experiments (affinity column chromatography and binding studies with isolated proteins) have shown that alpha B-crystallin interacts directly with actin and, in particular, with desmin filaments. The immunocytochemical localization of alpha B-crystallin within the cardiomyocytes showed that the protein is distributed exclusively in the central region of the I bands (Z lines), where desmin is localized. In vitro studies have further shown that the binding affinity of alpha B-crystallin to actin and desmin filaments increases considerably at slightly acidic pH (6.5) or after a heat treatment (45 degrees C). Moreover, alpha B-crystallin was found to prevent effectively the tendency of actin filaments to form aggregates (i.e., paracrystals) at acidic pH. These in vitro data suggest a protective ro...
(23) Erythrokeratoderma variabilis (Mendes da Costa's syndrome)
Authors: W.F.G. Tucker, C.I. Harrington
Journal: British Journal of Dermatology (1986)

Journal Article (23) Erythrokeratoderma variabilis (Mendes da Costa's syndrome) Get access W.F.G. Tucker, Drs, W.F.G. Tucker, Drs Search for other works by this author on: Oxford Academic Google Scholar C.I. Harrington C.I. Harrington Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Page 68, https://doi.org/10.1111/j.1365-2133.1986.tb07718.x Published: 01 July 1986
Ultrasound guidance of Palmaz-Schatz intracoronary stenting with a combined intravascular ultrasound balloon catheter.
Authors: HMudra, VKlauss, RBlasini, MKroetz, JRieber, ERegar, KTheisen
Journal: Circulation (1994)

BACKGROUNDCoronary stenting in conjunction with coronary angioplasty is a valuable tool for treatment of severe coronary dissection and is effective in reducing the frequency of restenoses. Evidence is increasing that the lumen gain within the stent is negatively correlated with the rate of subacute closures and restenoses. Since the assessment of radiolucent coronary stents and complex lumen morphologies by angiography is limited, we hypothesized that the use of a balloon catheter with integrated intravascular ultrasound (IVUS) facility for stent deployment and guidance of its expansion could improve the acute lumen gain without relevant procedural prolongation.METHODS AND RESULTSDeployment of a single Palmaz-Schatz coronary stent with the combined imaging balloon catheter alone was successful in 18 of 20 patients eligible for this study. Corresponding measurements of minimal lumen diameter (MLD) by angiography and IVUS could be performed in 16 patients, revealing a close correlation between the two meth...
A reassessment of the echocardiogram in mitral stenosis.
Authors: G DCope, J AKisslo, M LJohnson, V SBehar
Journal: Circulation (1975)

Echocardiographic and cardiac catheterization findings were compared in 61 patients with mitral stenosis without other significant lesions in an attempt to determine the clinical usefulness of echocardiography in the assessment of such patients. There was a poor correlation between the E-F slope on the echocardiogram and the calculated mitral valve area (r = 0.51). A review of reported data relating the E-F slope to mitral valve area indicated that echocardiographic assessment of mitral valve area had low sensitivity and specificity. The amplitude of excursion of the anterior leaflet did not differ significantly in patients undergoing valvotomy and those undergoind valve replacement. The data obtained suggest that while the echocardiogram is a reliable method of diagnosing mitral stenosis, the E-F slope is an unreliable index of the severity of the lesion.
Diseases of the Anus and Rectum.
Journal: JAMA (1901)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Isolated lichen planus of the lip
Authors: S.J.R. Allan, P.K. Buxton
Journal: British Journal of Dermatology (1996)

Journal Article Isolated lichen planus of the lip Get access S.J.R. Allan, S.J.R. Allan Department of Dermatology, Royal Infirmary of Edinburgh NHS Trust Search for other works by this author on: Oxford Academic Google Scholar P.K. Buxton P.K. Buxton Department of Dermatology, Royal Infirmary of Edinburgh NHS Trust Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 135, Issue 1, 1 July 1996, Pages 145–146, https://doi.org/10.1111/j.1365-2133.1996.tb03631.x Published: 01 July 1996
Cardiac epinephrine synthesis. Regulation by a glucocorticoid.
Authors: BKennedy, M GZiegler
Journal: Circulation (1991)

BACKGROUNDThe heart can synthesize epinephrine. Homogenates of rat heart, which contain the enzymes phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase (NMT), methylate norepinephrine to form epinephrine. The cardiac atrium contains primarily PNMT and the cardiac ventricle contains both PNMT and NMT.METHODS AND RESULTSRats were given the glucocorticoid dexamethasone at doses ranging from 0.2 to 20 mg/kg. Twenty-four hours later, cardiac atria, ventricle, skeletal muscle, and adrenal had increases in PNMT activity to as much as 230% of baseline. NMT activity was unchanged. Longer-term treatment with 1 mg/kg dexamethasone daily for 12 days increased cardiac PNMT activity about fivefold and also increased atrial epinephrine levels. Dexamethasone did not alter ventricular epinephrine levels but increased levels of both PNMT and catechol-O-methyltransferase, the major catabolic enzyme for epinephrine. After dexamethasone treatment, greater volumes of anti-PNMT antiserum were neede...
Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure.
Authors: J GMotwani, M KFenwick, J JMorton, A DStruthers
Journal: Circulation (1992)

BACKGROUNDTen chronic heart failure patients were studied on three occasions in randomized double-blind fashion to compare the acute hemodynamic, neurohormonal, and renal sodium-handling responses to 1 mg captopril versus 25 mg captopril, both in the absence of loop diuretic therapy and during furosemide-stimulated natriuresis.METHODS AND RESULTSCompared with placebo, 1 mg captopril caused nonsignificant decreases in mean arterial pressure and circulating angiotensin II level and had no effect on glomerular filtration rate as determined by 51Cr-EDTA elimination. Captopril (25 mg) produced marked suppression of serum angiotensin II with or without oral furosemide (both p less than 0.002), a marked decrease in mean arterial pressure (p less than 0.001) that was accentuated by furosemide (p less than 0.00001), and a decrease in glomerular filtration rate (p = 0.0007). No difference from placebo in renal sodium excretion was noted with either 1 or 25 mg captopril in the absence of furosemide. In contrast, whi...
Application of Artificial Intelligence For Real-Time Anatomical Recognition During Endoscopic Ultrasound Evaluation: A Pilot Study
Authors: C Robles-Medranda, R Oleas, R Del Valle, JC Mendez, J Alcivar-Vasquez, M Puga-Tejada, H Pitanga-Lukashok
Journal: Endoscopy (2021)

Aims We aimed to develop an artificial intelligence model that recognizes in real-time the anatomical structures during EUS evaluations.
Hemodynamic correlates of the normal aortic valve echogram. A study of sound, flow, and motion.
Authors: SLaniado, EYellin, RTerdiman, IMeytes, JStadler
Journal: Circulation (1976)

The aortic  echogram was recorded in open chest dogs simultaneously with aortic flow, acceleration of flow, aortic and left ventricular pressures, and intracardiac phonocardiograms. Comparison of echographic with hemodynamic data showed the following: The aortic  started its opening with the onset of flow, at the same point that left ventricular pressure exceeded aortic pressure. Complete  opening preceded peak aortic flow by an average of 43 msec and the cusps started to move toward closure while flow was still accelerating. Final closure of the  was achieved at the time of zero flow and preceded the aortic second sound by 4-10 msec. The echographically determined valve orifice area correlated well with aortic stroke volume (r = 0.94). The intensity of the aortic first sound was related to peak acceleration of aortic flow. The intensity of the second sound was not related to the amplitude of cusp motion but correlated well with the aortic pressure at the time of closure and with pea...
Left ventricular outflow tract obstruction due to systolic anterior motion of the anterior mitral leaflet in patients with concentric left ventricular hypertrophy.
Authors: B JMaron, J SGottdiener, W CRoberts, W LHenry, D DSavage, S EEpstein
Journal: Circulation (1978)

Patients with hypertrophic cardiomyopathy (i.e., asymmetric septal hypertrophy) may show obstruction to left ventricular outflow under basal conditions or with provocative maneuvers. The presence of dynamic left ventricular outflow tract obstruction in patients with concentric ventricular wall thickening (but without abnormalities of the aortic valve) has been less well appreciated. Clinical and morphologic features of five patients with nondilated left ventricles and with left ventricular outflow obstruction are presented. In each patient peak systolic pressure gradients between left ventricle and systematic artery were measured at cardiac catheterization and ranged from 60-140 mm Hg under basal conditions or with provocation. Each patient had echocardiographically documented systolic anterior motion of the anterior mitral leaflet, which was apparently responsible for the outflow obstruction, and concentric left ventricular wall thickening (septal-free wall thickness ratio of less than 1.3). Two of the f...
Developmental changes in membrane Ca2+ and K+ currents in fetal, neonatal, and adult rabbit ventricular myocytes.
Authors: T VHuynh, FChen, G TWetzel, W FFriedman, T SKlitzner
Journal: Circulation Research (1992)

Whole-cell calcium current (ICa) and inwardly rectifying potassium current (IK1) were studied in 21-day fetal, 28-day fetal (total gestation, 31 days), 2-5-day neonatal, and adult rabbit ventricular myocytes isolated by enzymatic dissociation. Whole-cell peak ICa and IK1 at -100 mV increased significantly after birth. Cell size approximated from cell membrane capacitance also increased with age, with the most significant increase occurring after birth. When normalized to cell surface area, peak ICa density increased from day 21 of gestation to the neonate and then increased again from neonate to adult. In all age groups, peak ICa occurred at a test potential of +10 mV, and the shape of the Ca2+ current-voltage relation did not change with age. These findings suggest that there are no significant developmental changes in the voltage dependence of ICa. Therefore, the measured age-related increase in Ca2+ current density may result from increased channel expression. IK1 also exhibited a pattern of increasing...
Electrophysiological properties of cultured dog myocytes obtained by endomyocardial biopsy.
Authors: SSakai, TTokimasa, MNohara, YKoga, TAkasu, HToshima
Journal: Circulation Research (1989)

Right ventricular cardiac tissue (10-20 mg wet weight) was obtained from anesthetized adult dogs by endomyocardial biopsy. The biopsy could be repeated in one dog every 2 weeks for up to 3 months. Fifty to 200 cardiomyocytes, dispersed with collagenase and trypsin, were collected by centrifugation of the cells with 50% polysucrose-sodium diatrizoate solution (Ficoll-Paque). Single cardiomyocytes were suspended in a minimum essential medium containing 20% fetal bovine serum and 8-bromoadenosine 3': 5'-cyclic monophosphate (0.1 mM) for up to 3 weeks. Approximately 70-80% of the cultured cardiomyocytes were rod shaped after 24 hours (10-20% after 7 days). Cytoplasmic organelles of the cultured cells, examined with a transmission electron microscope, were within the normal range of canine heart morphology in vivo. Resting membrane potential of the cells was about -80 mV when superfused with a Krebs' solution containing 4.7 mM potassium ions. The action potential lasted for 300 msec and had a peak amplitude of...
Arachidonic acid elicits endothelium-dependent release from the rabbit aorta of a constrictor prostanoid resembling prostaglandin endoperoxides.
Authors: P JPagano, LLin, W CSessa, ANasjletti
Journal: Circulation Research (1991)

This study was designed to investigate the mediator(s) of endothelium-dependent arterial constrictor responses evoked by arachidonic acid in vitro. A segment of descending rabbit thoracic aorta was isolated and perfused (1-2 ml/min) with oxygenated Krebs' bicarbonate buffer. Changes in the vascular smooth muscle-contracting activity of the aortic effluent were detected by superfusion bioassay using either strips of rabbit aorta or rings of dog saphenous vein, both denuded of endothelium and exposed to indomethacin (10 microM). Arachidonic acid (5-50 micrograms) injected into the inflow of the perfused aorta caused a dose-related increase in the vascular smooth muscle-contracting activity of the aortic effluent, whereas arachidonic acid added directly into the aortic effluent did not. The arachidonic acid-induced elevation of vascular smooth muscle-contracting activity in the aortic effluent was not apparent when indomethacin (10 microM) was added to the aortic inflow to inhibit cyclooxygenase, when the en...
Long-term graft patency (3 years) after coronary artery surgery. Effects of aspirin: results of a VA Cooperative study.
Authors: SGoldman, JCopeland, TMoritz, WHenderson, KZadina, TOvitt, K BKern, GSethi, G VSharma, SKhuri
Journal: Circulation (1994)

BACKGROUNDThe long-term success of coronary bypass surgery is dependent on graft patency after surgery. This trial was designed to determine if aspirin improved saphenous vein graft or internal mammary artery (IMA) graft patency between 1 and 3 years after coronary artery bypass grafting (CABG).METHODS AND RESULTSAfter receiving aspirin 325 mg/d for 1 year after CABG and undergoing a 1-year postoperative cardiac catheterization, patients were randomized to receive either aspirin (325 mg) or placebo for 2 additional years. Angiography was performed 3 years after surgery to determine the primary end point-saphenous vein graft patency in 288 patients and IMA graft patency in 167 patients. At 3 years after CABG, the saphenous vein graft occlusion rate was 17.0% (62 of 365) for patients treated with aspirin compared with 19.7% (74 of 376) for those who received placebo (P = .404). For saphenous vein grafts that were patent at 1 year, the occlusion rate at 3 years was 4.8% (15 of 313) for patients treated with ...
Risk Factors Related To Advanced Colorectal Neoplasia In Colorectal Cancer Screening – Interim Results Of Multicentric Prospective Study
Authors: T Grega, G Vojtechova, O Ngo, O Majek, M Zavoral, S Suchanek
Journal: Endoscopy (2021)

Aims The lifetime risk of developing colorectal cancer in average risk population is 4.4 %. The prevalence of advanced colorectal neoplasia in the screening population shows great diversity around 3-12 % depending on multiple risk factors. The aim of the study was to determine the risk factors associated with the incidence of advanced colorectal neoplasia in the screening population.