tbuckley/cabot-search huggingface dataset:
Abstract P334: Distribution of Coronary Artery Calcium Score in a Multi-Ethnic Admixed Population: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
Authors: Marcio S Bittencourt, Alexandre C Pereira, Henrique L Staniak, Itamar S Santos, Rodolfo Sharovsky, Luz M Gomez, Michael J Blaha, Isabela M Bensenor, Paulo A Lotufo
Journal: Circulation (2014)

Introduction: Coronary artery calcium (CAC) is a marker of coronary atherosclerosis burden and is a strong predictor of cardiovascular events and overall mortality, especially in White populations. The distribution of CAC has been determined for a number of predominantly White populations; however, the distribution in ethnically admixed groups has not been well established. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort with 15, 105 participants with an ethnic diversity (White, 52.2%; Brown, 28.2%; Black,16.1%; Asian, 2.5% and Native, 1.0%) is an unique opportunity to explore CAC scores differences among admixed populations. Hypothesis: to compare CAC scores obtained from an admixed population in Brazil with the results from the Multi Ethnic Study of Atherosclerosis (MESA). Methods: From the 15105 participants of ELSA-Brasil, a prospective study that enrolled civil servants aged 35 to 74 years, CAC scoring was performed on 3,400 individuals at the Sao Paulo site. Similar to previous studies, individuals with self-reported cardiovascular diseases or treated diabetes were excluded from the analysis. The final population included 2,753 individuals (men = 54%; median age = 48 years). Percentiles of CAC distribution were estimated using a two-part local regression fitting model, adapted to zero-inflated data and then compared to MESA CAC percentiles. Testing of the predictive role of age (years), sex, and ethnicity was done modeling a zero-inflated distribution for continuous data. Results: For the discrete part of CAC modelling, age, sex and ethnicity were predictors of CAC prevalence (CAC&gt;0). For the ELSA-Brasil sample, increasing age (OR=1.14, p&lt;0.001), male sex (OR: 3.61, p&lt;0.001), and White ethnicity (OR=1.46 (against Blacks), p=0.02) were significantly associated with increased odds of having CAC&gt;0. Different from expected, for the continuous part of CAC modelling, only age (p=0.02) was significantly associated with increased CAC values. Compared to MESA percentiles, the participants or ELSA-Brasil presented, overall, lower CAC values. Conclusions: Among this sample of apparently healthy Brazilian adults, we did observe significant differences in CAC prevalence by ethnicity, sex, and age. In contrast with MESA, the difference regarding the amount of CAC between men and women were smaller, suggesting an increased risk of Brazilian women compared to US women.
Definition of a natural killer NKR-P1A+/CD56-/CD16- functionally immature human NK cell subset that differentiates in vitro in the presence of interleukin 12.
Authors: I M Bennett, O Zatsepina, L Zamai, L Azzoni, T Mikheeva, B Perussia
Journal: The Journal of Experimental Medicine (1996)

Human natural killer (NK) cell differentiation from immature lineage negative (Lin-) umbilical cord blood cells was examined in vitro. Cells expressing differentiation antigens of mature NK cells (CD56, CD16, CD2, CD8, NKR-P1A) were generated from Lin- cells cultured with interleukin (IL)-2 and a murine bone marrow stromal cell line expressing the human membrane-bound form of stem cell factor. Two subsets of NK cells were identified in these cultures: one expressed both NKR-P1A and CD56 and, in variable proportions, all other NK cell differentiation antigens; the second subset expressed only NKR-P1A and, unlike the former, was not cytotoxic. Neither subset expressed interferon (IFN)-gamma mRNA even after stimulation with phorbol di-ester and Ca2+ ionophore, but both expressed tumor necrosis factor alpha mRNA and the cytotoxic granule-associated proteins TIA-1, perforin, and serine esterase-1. After 10-d culture with IL-2, IL-12, and irradiated B lymphoblastoid cells, approximately 45% of the NKR-P1A+/ CD56- cells became CD56+, and the same cultures contained cells capable of cytotoxicity and of IFN-gamma production. These results indicate that NKR-P1A expression in the absence of other NK cell markers defines an intermediate, functionally immature stage of NK cell differentiation, and that effector functions develop in these cells, concomitantly with CD56 expression, in the presence of IL-12. These cells likely represent the counterpart of a CD3-/NKR-P1A+/ CD56-/CD16- cell subset that, as shown here, is present both in adult and neonatal circulating lymphocytes.
MICU1 Controls Both the Threshold and Cooperative Activation of the Mitochondrial Ca2+ Uniporter
Authors: György Csordás, Tünde Golenár, Erin L. Seifert, Kimberli J. Kamer, Yasemin Sancak, Fabiana Perocchi, Cynthia Moffat, David Weaver, Sergio de la Fuente Perez, Roman Bogorad, Victor Koteliansky, Jeffrey Adijanto, Vamsi K. Mootha, György Hajnóczky
Journal: Cell Metabolism (2013)
MID-TERM CLINICAL OUTCOME OF CATANIA™ CORONARY STENT SYSTEM WITH NANOTHIN POLYZENE®-F IN A REAL WORLD UNSELECTED POPULATION: PRELIMINARY RESULTS: I2 POSTER CONTRIBUTIONS
Authors: Alessio La Manna, Alessandra Sanfilippo, Sergio Monaco, Maria Elena Di Salvo, Irene Cascone, Daniele Giacoppo, Piera Capranzano, Davide Capodanno, Corrado Tamburino
Journal: Journal of the American College of Cardiology (2010)
Effect of pirfenidone, a novel antifibrotic agent, on PDGF-induced intracellular signaling in rat hepatic stellate cells
Authors: A. Di Sario, E. Bendia, G. Svegliati Baroni, S. Saccomanno, R. Ridolfi, U. Ugili, L. Trozzi, A.M. Jezequel, A. Benedetti
Journal: Journal of Hepatology (2000)
Positive selection of T cells: rescue from programmed cell death and differentiation require continual engagement of the T cell receptor.
Authors: P Kisielow, A Miazek
Journal: The Journal of Experimental Medicine (1995)

Positive selection of T cells is a complex developmental process generating long-lived, functionally mature CD4+CD8- and CD4-CD8+ cells from short-lived, immature CD4+CD8+ precursors. The process is initiated in the thymus by interaction of the alpha beta TCR with molecules encoded by the MHC, occurs without cell division, and involves rescue from programmed cell death (PCD), as well as induction of differentiation and maturation of selected precursors. It is unclear whether development of small, positively selected CD4+CD8+ thymocytes (characterized by up-regulated levels of TCR and CD69 molecules) depends on further interactions with MHC molecules and, if so, whether such interactions are required for survival, for maturation, or for both. The involvement of the TCR and/or CD4/CD8 coreceptors in transmitting additional signals is also unknown. We have examined these questions by analyzing survival and differentiation of early (CD4+CD8+TCRhi) and later (CD4-CD8+TCRhi) postselection stages of thymocytes from normal and bcl-2 transgenic mice expressing transgenic, class I MHC-restricted TCR, upon intrathymic transfer into recipients that lacked ligands either for both the TCR and CD8 coreceptor, or for the TCR only. The results provide direct evidence that induction of differentiation of CD4+CD8+ thymocytes by recognition of MHC molecules does not rescue them from PCD and is insufficient to activate the entire maturation program. Both processes require continual engagement of the TCR by positively selecting MHC molecules that, at least in the case of class I MHC-restricted CD4-CD8+ T cells, cannot be substituted by the engagement of coreceptor alone.
The Pneumococcal Vaccine
Authors: Robert H. Pantell
Journal: JAMA (1979)

A new polyvalent pneumococcal vaccine (Pneumovax) was released in February 1978. In an effort to chronicle the dissemination of the vaccine to high-risk patients, we prospectively followed up a single clinic population and conducted a telephone survey of three neighborhood health centers, two private practices, and a university hematology clinic. Three months after notification of the vaccine arrival, physicians in the prospectively chronicled clinic had immunized six of 12 patients with sickle cell disease, five of 80 patients with chronic obstructive pulmonary disease, three of 225 patients with diabetes, and three of 45 patients older than 80 years. Immunization policy in the other clinics surveyed varied greatly. As an attempt to curb low-prevalence, high-severity illness in a small target population, the pneumococcal vaccine presents a new set of problems in the systematic implementation of an immunization. (<i>JAMA</i>241:2272-2274, 1979)
Expression of discoidin domain receptor 1 tyrosine kinase on the human bronchial epithelium
Authors: O. Sakamoto, M. Suga, T. Suda, M. Ando
Journal: European Respiratory Journal (2001)

Discoidin domain receptor 1 (DDR1) tyrosine kinases constitute a novel family of receptors characterized by a unique structure in the ectodomain (discoidin-I domain). The DDR1 ligand is the extracellular matrix protein collagen. To identify receptor tyrosine kinases (RTKs) involved in control of growth and differentiation of human bronchial epithelial (HBE) cells, a polymerase chain reaction-based search for RTKs in HBE cells was performed. DDR1 was the most abundant clone identified. Northern analysis detected a 3.6 kb DDR1 messenger ribonucleic acid (mRNA) expressed in HBE cells and transformed HBE lines, BET-1A and BEAS-2B. In addition, fluorescence-activated cell sorter (FACS) analyses using an anti-DDR1 antibody showed that DDR1 was expressed on HBE cells and two HBE lines. Immunohistochemical staining using human bronchial tissue demonstrated that DDR1 was mainly expressed at the basolateral cell surface of the bronchial epithelium. Furthermore, immunostaining of type IV collagen, a major component of the basement membrane, clearly showed that the basement membrane was closely attached to the basal surface of the bronchial epithelium. Since collagen binds to and activates discoidin domain receptor 1 tyrosine kinase, colocalization of discoidin domain receptor 1 and its ligand type IV collagen demonstrates a potential interaction of discoidin domain receptor 1 on the bronchial epithelium with type IV collagen. Further study of this interaction may define the functional significance of the collagen-discoidin domain receptor 1 signalling pathway in health and in disease.
PLASTICITY OF THE SPINAL NEURAL CIRCUITRY AFTER INJURY
Authors: V. Reggie Edgerton, Niranjala J.K. Tillakaratne, Allison J. Bigbee, Ray D. de Leon, Roland R. Roy
Journal: Annual Review of Neuroscience (2004)

Motor function is severely disrupted following spinal cord injury (SCI). The spinal circuitry, however, exhibits a great degree of automaticity and plasticity after an injury. Automaticity implies that the spinal circuits have some capacity to perform complex motor tasks following the disruption of supraspinal input, and evidence for plasticity suggests that biochemical changes at the cellular level in the spinal cord can be induced in an activity-dependent manner that correlates with sensorimotor recovery. These characteristics should be strongly considered as advantageous in developing therapeutic strategies to assist in the recovery of locomotor function following SCI. Rehabilitative efforts combining locomotor training pharmacological means and/or spinal cord electrical stimulation paradigms will most likely result in more effective methods of recovery than using only one intervention.
The Clinical Utility of a Published Nomogram to Predict Aminoglycoside Nephrotoxicity
Authors: Y. W. Francis Lam
Journal: JAMA (1986)

Moore and colleagues recently published a nomogram for predicting the risk of aminoglycoside nephrotoxicity. This study was undertaken to evaluate the clinical usefulness of this nomogram. The nephrotoxicity risk scores of 61 patients were determined using parameters suggested by Moore et al. Thirteen patients (21%) could not be scored because their initial creatinine clearances exceeded the upper limit of the nomogram. Six patients (9.8%) developed nephrotoxicity (defined as a ≥50% decrease in creatinine clearance). In five of these patients in whom risk scores could be determined, the scores were estimated at 14% or less. Twenty patients had risk scores of 10% or more (four patients, ≥50%) without developing nephrotoxicity. These results demonstrate that this nomogram may have limited clinical application in predicting patients likely to develop aminoglycoside nephrotoxicity. (<i>JAMA</i>1986;255:639-642)
Early and late nasal symptom response to allergen challenge
Authors: H. Grønborg, H. Bisgaard, F. Rømeling, N. Mygind
Journal: Allergy (1993)

We challenged 30 pollen‐sensitive volunteers with allergen, recorded symptoms and signs over a 10‐h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment with the glucocorticosteroid budesonide (200 μg twice daily) for 14 d and with placebo in a double‐blind, cross‐over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose‐blowings, and of a sustained nasal blockage These symptoms did not have a well‐defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72% reduction; P &lt;0.01), a moderate effect on discharge (37% reduction; P &lt;0.01), and a slight effect on blockage (17% reduction of nasal inspiratory peak flow rate; P &lt;0.02). The degree of inhibition of the rechallenge response was similar to the effect on the initial early response. The effect on the late response was very pronounced for all symptoms and signs (97% reduction of sneezes 76% reduction of nose‐blowings, 96% reduction of blockage; P &lt;0.01). In conclusion, we found it difficult in the individual subject to identify a well‐defined late symptom response by criteria similar to those employed to characterize the late response in the bronchi. The effect of budesonide was more marked on sneezing than on blockage, and the drug was considerably more effective on the late response than on the early response.
Metabolic dependence of red cell deformability
Authors: Robert I. Weed, Paul L. LaCelle, Edward W. Merrill
Journal: Journal of Clinical Investigation (1969)

The contribution of the metabolic state of human erythrocytes to maintenance of cellular deformability was studied during and after in vitro incubation in serum for periods up to 28 hr. An initial loss of membrane deformability became apparent between 4 and 6 hr when cellular adenosine triphosphate (ATP) levels were approximately 70% of initial values. Membrane deformability then remained stable between 6 and 10 hr. After 10 hr, when cellular ATP had decreased to < 15% of initial values, progressive parallel changes occurred in red cell calcium which increased 400% by 24 hr and in the viscosity of red cell suspensions which had risen 500-750% at 24 hr. A further progressive decrease in membrane deformability also occurred and was reflected by a 1000% increase in negative pressure required to deform the membrane. Red cell filterability decreased to zero as the disc-sphere shape transformation ensued. These changes were accompanied by an increase in ghost residual hemoglobin and nonhemoglobin protein. Regeneration of ATP in depleted cells by incubation with adenosine produced significant reversal of these changes, even in the presence of ouabain. Introduction of calcium into reconstituted ghosts prepared from fresh red cells mimicked the depleted state, and introduction of ATP, ethylenediamine tetraacetate (EDTA), and magnesium into depleted cells mimicked the adenosine effects in intact depleted cells. ATP added externally to 24-hr depleted cells was without effect. Simultaneous introduction of EDTA, ATP, or magnesium along with calcium into reconstituted ghosts prevented the marked decrease in deformability produced by calcium alone. Incorporation of adenosine diphosphate (ADP), nicotinamide adenine dinucleotide (NAD), NAD phosphate (NADP), NADP, reduced form (NADPH), glutatione, reduced form (GSH), inosine triphosphate (ITP), guanosine triphosphate (GTP), and uridine triphosphate (UTP) was without effect. These data suggest that a major role of ATP in maintenance of red cell viability relates to preservation of red cell membrane deformability. It is proposed that the changes seen in the physical properties of ATP-depleted erythrocytes represent ATP-calcium-dependent sol-gel changes occurring at the interface between the membrane and the cell interior, and that the sol-gel balance determines membrane deformability.
Transgenic and Knockout Models of Neuropsychiatric Disordersedited by Gene S. Fisch, Ph.D., and Jonathan Flint, M.D., M.R.C.Psych. Totowa, N.J., Humana Press, 2006, 312 pp., $145.00.
Authors: KAREN E. STEVENS
Journal: American Journal of Psychiatry (2008)
Engineering a Prostate-Specific Membrane Antigen–Activated Tumor Endothelial Cell Prodrug for Cancer Therapy
Authors: Samuel R. Denmeade, Annastasiah M. Mhaka, D. Marc Rosen, W. Nathaniel Brennen, Susan Dalrymple, Ingrid Dach, Claus Olesen, Bora Gurel, Angelo M. DeMarzo, George Wilding, Michael A. Carducci, Craig A. Dionne, Jesper V. Møller, Poul Nissen, S. Brøgger Christensen, John T. Isaacs
Journal: Science Translational Medicine (2012)

A prostate-specific membrane antigen–activated prodrug selectively kills cancer cells and is being tested in patients with advanced cancer.
Growth and differentiation of conducting airway epithelial cells in culture
Authors: R Wu, YH Zhao, MM Chang
Journal: European Respiratory Journal (1997)

The development of routine techniques for the isolation and in vitro maintenance of conducting airway epithelial cells in a differentiated state provides an ideal model to study the factors involved in the regulation of the expression of mucociliary differentiation. Several key factors and conditions have been identified. These factors and conditions include the use of biphasic culture technique to achieve mucociliary differentiation, the use of such stimulators as the thickness of collagen gel substratum, the calcium level, and vitamin A, and such inhibitors as the growth factors, epidermal growth factor and insulin, and steroid hormones, for mucous cell differentiation. Using the defined culture medium, the life cycle of the mucous cell population in vitro has been investigated. It was demonstrated that the majority of the mucous cell population in primary cultures is not involved in the replication of deoxyribonucleic acid (DNA). However, the mucous cell type is capable of self-renewal in culture, and this reproduction is vitamin A dependent. Furthermore, differentiation from nonmucous to mucous cell type can be demonstrated by adding back a positive regulator such as vitamin A to the "starved" culture. Cell kinetics data suggest that vitamin A-dependent mucous cell differentiation in culture is a DNA replication-independent process, and the process is inhibited by transforming growth factor-beta1.
Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler sonographic screening in a large family
Authors: Elisabetta Buscarini, Luigi Buscarini, Cesare Danesino, Mauro Piantanida, Giuseppe Civardi, Pietro Quaretti, Sandro Rossi, Michele Di Stasi, Matteo Silva
Journal: Journal of Hepatology (1997)
A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma.
Authors: M S Ernstoff, S Nair, R R Bahnson, L M Miketic, B Banner, W Gooding, R Day, T Whiteside, T Hakala, J M Kirkwood
Journal: Journal of Clinical Oncology (1990)

This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously.
Fluorescence Resonance Energy Transfer–Based Sensor Camui Provides New Insight Into Mechanisms of Calcium/Calmodulin-Dependent Protein Kinase II Activation in Intact Cardiomyocytes
Authors: Jeffrey R. Erickson, Ruchi Patel, Amanda Ferguson, Julie Bossuyt, Donald M. Bers
Journal: Circulation Research (2011)

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a key mediator of intracellular signaling in the heart. However, the tools currently available for assessing dynamic changes in CaMKII localization and activation in living myocytes are limited.We use Camui, a novel FRET-based biosensor in which full-length CaMKII is flanked by CFP and YFP, to measure CaMKII activation state in living rabbit myocytes.We show that Camui and mutant variants that lack the sites of CaMKII autophosphorylation (T286A) and oxidative regulation (CM280/1VV) serve as useful biosensors for CaMKIIδ activation state. Camui (wild-type or mutant) was expressed in isolated adult cardiac myocytes, and localization and CaMKII activation state were determined using confocal microscopy. Camui, like CaMKIIδ, is concentrated at the z-lines, with low baseline activation state. Camui activation increased directly with pacing frequency, but the maximal effect was blunted with the T286A, consistent with frequency-dependent phosphorylation of CaMKII at T286 mainly at high-frequency and high-amplitude Ca transients. Camui was also activated by 4 neurohormonal agonists. Angiotensin II and endothelin-1 activated Camui, largely through an oxidation-dependent mechanism, whereas isoproterenol- and phenylephrine-mediated mechanisms had a significant autophosphorylation-dependent component.Camui is a novel, nondestructive tool that allows spatiotemporally resolved measurement of CaMKII activation state in physiologically functioning myocytes. This represents a first step in using Camui to elucidate key mechanistic details of CaMKII signaling in live hearts and myocytes.