tbuckley/cabot-search huggingface dataset:
Both Protein Kinase A and Exchange Protein Activated by cAMP Coordinate Adhesion of Human Vascular Endothelial Cells
Authors: Stuart J. Netherton, Jayda A. Sutton, Lindsay S. Wilson, Rhonda L. Carter, Donald H. Maurice
Journal: Circulation Research (2007)

cAMP regulates integrin-dependent adhesions of vascular endothelial cells (VECs) to extracellular matrix proteins, their vascular endothelial cadherin-dependent intercellular adhesions, and their proliferation and migration in response to growth and chemotactic factors. Previously, we reported that cAMP-elevating agents differentially inhibited migration of human VECs isolated from large vascular structures (macro-VECs, human aortic endothelial cells [HAECs]) or small vascular structures (micro-VECs, human microvascular endothelial cells [HMVECs]) and that cAMP hydrolysis by phosphodiesterase (PDE)3 and PDE4 enzymes was important in coordinating this difference. Here we report that 2 cAMP-effector enzymes, namely protein kinase (PK)A and exchange protein activated by cAMP (EPAC), each regulate extracellular matrix protein-based adhesions of both macro- and micro-VECs. Of interest and potential therapeutic importance, we report that although specific pharmacological activation of EPAC markedly stimulated adhesion of micro-VECs to extracellular matrix proteins when PKA was inhibited, this treatment only modestly promoted adhesion of macro-VECs. Consistent with an important role for cAMP PDEs in this difference, PDE3 or PDE4 inhibitors promoted EPAC-dependent adhesions in micro-VECs when PKA was inhibited but not in macro-VECs. At a molecular level, we identify multiple, nonoverlapping, PKA- or EPAC-based signaling protein complexes in both macro- and micro-VECs and demonstrate that each of these complexes contains either PDE3B or PDE4D but not both of these PDEs. Taken together, our data support the concept that adhesion of macro- and micro-VECs is differentially regulated by cAMP and that these differences are coordinated through selective actions of cAMP at multiple nonoverlapping signaling complexes that contain PKA or EPAC and distinct PDE variants.
Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells
Authors: Kan Cao, John J. Graziotto, Cecilia D. Blair, Joseph R. Mazzulli, Michael R. Erdos, Dimitri Krainc, Francis S. Collins
Journal: Science Translational Medicine (2011)

Shown previously to extend longevity in animals, the drug rapamycin might serve as a treatment for a human premature aging syndrome.
The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation
Authors: T Lion, F Watzinger, S Preuner, H Kreyenberg, M Tilanus, R de Weger, J van Loon, L de Vries, H Cavé, C Acquaviva, M Lawler, M Crampe, A Serra, B Saglio, F Colnaghi, A Biondi, J J M van Dongen, M van der Burg, M Gonzalez, M Alcoceba, G Barbany, M Hermanson, E Roosnek, C Steward, J Harvey, F Frommlet, P Bader
Journal: Leukemia (2012)
Association of variants in genes encoding for macrophage-related functions with clinical outcome in patients with locoregional gastric cancer
Authors: Y. Sunakawa, S. Stremitzer, S. Cao, W. Zhang, D. Yang, T. Wakatsuki, Y. Ning, S. Yamauchi, S. Stintzing, A. Sebio, R. El-khoueiry, S. Matsusaka, A. Parekh, A. Barzi, M. Azuma, M. Watanabe, W. Koizumi, H.-J. Lenz
Journal: Annals of Oncology (2014)
Effects of Intracoronary CD34 <sup>+</sup> Stem Cell Transplantation in Nonischemic Dilated Cardiomyopathy Patients
Authors: Bojan Vrtovec, Gregor Poglajen, Luka Lezaic, Matjaz Sever, Dragoslav Domanovic, Peter Cernelc, Aljaz Socan, Sonja Schrepfer, Guillermo Torre-Amione, François Haddad, Joseph C. Wu
Journal: Circulation Research (2012)

CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance.We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response.Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39).Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.
The feedback regulation of angiotensinogen production by components of the renin-angiotensin system.
Authors: H C Herrmann, V J Dzau
Journal: Circulation Research (1983)

The in vivo generation of angiotensin appears to be dependent on both plasma renin and angiotensinogen concentrations. Much less is known about the control of hepatic angiotensinogen synthesis and release, as compared to that of renin. In this study, we examined the feedback regulation of angiotensinogen synthesis and release by various components of the renin-angiotensin system, using an in vitro rat liver slice system. Livers were removed for study from rats which were subjected to various systemic infusions or physiological perturbations. Infusion of angiotensin II has been reported to increase angiotensinogen release rate. However, infusion of angiotensin I (with simultaneous suppression of plasma renin by antirenin antibody infusion and angiotensin II production by captopril administration) had no effect on the angiotensinogen release rate. Direct infusion of renin in rats treated with captopril resulted in further suppression of the angiotensinogen release rate, compared with those given captopril alone. We postulate that renin (or des-angiotensin I-angiotensinogen) inhibits the angiotensinogen release rate, whereas angiotensin II stimulates it. Angiotensin I has no effect on angiotensinogen release rate. This hypothesis was evaluated further in rats with various physiological states. Indeed, when conditions were such that the renin-angiotensin system was completely suppressed, such as binephrectomy and antirenin antibody infusion, angiotensinogen release rate was markedly stimulated. When angiotensin II production was prevented by captopril treatment, angiotensinogen release rate declined. This appeared to be the case for all states of sodium balance. Thus, angiotensinogen release rate is subject to a complex feedback control by other components of the renin-angiotensin system.
Large‐Scale Fabrication of Free‐Standing, Micropatterned Silica Nanotubes Via a Hybrid Hydrogel‐Templated Route
Authors: Song Chen, Xuetao Shi, Shanmugavel Chinnathambi, Nobutaka Hanagata
Journal: Advanced Healthcare Materials (2013)

Free-standing, micropatterned silica nanotube membranes are in situ fabricated using a micropatterned silica-coated collagen hybrid hydrogel as template. They are substrate-free, and not only maintained their micropatterned microstructure well, but also exhibited strong cell contact guidance ability to direct cell alignment and differentiation, indicating their good potential for biomedical applications.
Subtracting “ought” from “is”: Descriptivism versus normativism in the study of human thinking
Authors: Shira Elqayam, Jonathan St. B. T. Evans
Journal: Behavioral and Brain Sciences (2011)

Abstract We propose a critique of normativism , defined as the idea that human thinking reflects a normative system against which it should be measured and judged. We analyze the methodological problems associated with normativism, proposing that it invites the controversial “is-ought” inference, much contested in the philosophical literature. This problem is triggered when there are competing normative accounts (the arbitration problem), as empirical evidence can help arbitrate between descriptive theories, but not between normative systems. Drawing on linguistics as a model, we propose that a clear distinction between normative systems and competence theories is essential, arguing that equating them invites an “is-ought” inference: to wit, supporting normative “ought” theories with empirical “is” evidence. We analyze in detail two research programmes with normativist features – Oaksford and Chater's rational analysis and Stanovich and West's individual differences approach – demonstrating how, in each case, equating norm and competence leads to an is-ought inference. Normativism triggers a host of research biases in the psychology of reasoning and decision making: focusing on untrained participants and novel problems, analyzing psychological processes in terms of their normative correlates, and neglecting philosophically significant paradigms when they do not supply clear standards for normative judgement. For example, in a dual-process framework, normativism can lead to a fallacious “ought-is” inference, in which normative responses are taken as diagnostic of analytic reasoning. We propose that little can be gained from normativism that cannot be achieved by descriptivist computational-level analysis, illustrating our position with Hypothetical Thinking Theory and the theory of the suppositional conditional. We conclude that descriptivism is a viable option, and that theories of higher mental processing would be better off freed from normative considerations.
Types of ovarian activity in women and their significance: the continuum (a reinterpretation of early findings)
Authors: J. B. Brown
Journal: Human Reproduction Update (2010)

BACKGROUNDThere are many types of ovarian activity that occur in women. This review provides information on the relationship between the hormone values and the degree of biological response to the hormones including the frequency and degree of uterine bleeding. The continuous process is termed the ‘Continuum’ and is thus similar to other processes in the body.
Identification of Molecular Pathway Aberrations in Uterine Serous Carcinoma by Genome-wide Analyses
Authors: Elisabetta Kuhn, Ren-Chin Wu, Bin Guan, Gang Wu, Jinghui Zhang, Yue Wang, Lei Song, Xiguo Yuan, Lei Wei, Richard B.S. Roden, Kuan-Tin Kuo, Kentaro Nakayama, Blaise Clarke, Patricia Shaw, Narciso Olvera, Robert J. Kurman, Douglas A. Levine, Tian-Li Wang, Ie-Ming Shih
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundUterine cancer is the fourth most common malignancy in women, and uterine serous carcinoma is the most aggressive subtype. However, the molecular pathogenesis of uterine serous carcinoma is largely unknown. We analyzed the genomes of uterine serous carcinoma samples to better understand the molecular genetic characteristics of this cancer.
Musculoskeletal ultrasound: taking sports medicine to the next level
Authors: Kimberly G Harmon, Francis G O'Connor
Journal: British Journal of Sports Medicine (2010)

Ultrasound (US) technology is rapidly revolutionising the way medicine is practiced at the point of care. US is currently utilised as an integral tool in multiple non-radiologic specialties including emergency medicine, anaesthesia, neurology, general surgery, endocrinology, physical medicine, rheumatology, paediatrics and family medicine.1,–,5 In primary care, in particular, US instruction is routinely incorporated in residency training to facilitate prenatal care in the office, assist in vascular access in the in-patient setting and manage the trauma patient in the emergency room.6 7 The incorporation of some component of US training in the education of medical students and residents in the United States is now considered routine.

Musculoskeletal (MSK) US has largely been ignored in North America for the past 25 years in favour of MRI. The last 5 years, however, has seen a renaissance for MSK US in North America as we strive to catch up to our European colleagues. The re-emergence of MSK US has been driven by technological advances which have made the instruments affordable, portable and practical for the office setting. US can be a cost-effective diagnostic tool in the evaluation of the patient with MSK pain8,–,10 and this has opened up new opportunities for both diagnostic and therapeutic interventions performed at the point of care.

The rush to utilise new technology, however, has created concerns. Who should use US? What type of training is required? How should …
Effect of Reducing Interns' Weekly Work Hours on Sleep and Attentional Failures
Authors: Steven W. Lockley, John W. Cronin, Erin E. Evans, Brian E. Cade, Clark J. Lee, Christopher P. Landrigan, Jeffrey M. Rothschild, Joel T. Katz, Craig M. Lilly, Peter H. Stone, Daniel Aeschbach, Charles A. Czeisler
Journal: New England Journal of Medicine (2004)

Knowledge of the physiological effects of extended (24 hours or more) work shifts in postgraduate medical training is limited. We aimed to quantify work hours, sleep, and attentional failures among first-year residents (postgraduate year 1) during a traditional rotation schedule that included extended work shifts and during an intervention schedule that limited scheduled work hours to 16 or fewer consecutive hours.
Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer
Authors: David O. Wilson, Joel L. Weissfeld, Arzu Balkan, Jeffrey G. Schragin, Carl R. Fuhrman, Stephen N. Fisher, Jonathan Wilson, Joseph K. Leader, Jill M. Siegfried, Steven D. Shapiro, Frank C. Sciurba
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

To study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population.We studied lung cancer related to radiographic emphysema and spirometric airflow obstruction in tobacco-exposed persons who were screened for lung cancer using chest computed tomography (CT).Subjects completed questionnaires, spirometry, and low-dose helical chest CT. CT scans were scored for emphysema based on National Emphysema Treatment Trial criteria. Multiple logistic regressions estimated the independent associations between various factors, including radiographic emphysema and airflow obstruction, and subsequent lung cancer diagnosis.Among 3,638 subjects, 57.5, 18.8, 14.6, and 9.1% had no, trace, mild, and moderate-severe emphysema, and 57.3, 13.6, 22.8, and 6.4% had no, mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] I), moderate (GOLD II), and severe (GOLD III-IV) airflow obstruction. Of 3,638 subjects, 99 (2.7%) received a lung cancer diagnosis. Adjusting for sex, age, years of cigarette smoking, and number of cigarettes smoked daily, logistic regression showed the expected lung cancer association with the presence of airflow obstruction (GOLD I-IV, odds ratio [OR], 2.09; 95% confidence interval [CI], 1.33-3.27). A second logistic regression showed lung cancer related to emphysema (OR, 3.56; 95% CI, 2.21-5.73). After additional adjustments for GOLD class, emphysema remained a strong and statistically significant factor related to lung cancer (OR, 3.14; 95% CI, 1.91-5.15).Emphysema on CT scan and airflow obstruction on spirometry are related to lung cancer in a high-risk population. Emphysema is independently related to lung cancer. Both radiographic emphysema and airflow obstruction should be considered when assessing lung cancer risk.
Autologous and Allogeneic Stem-Cell Transplantation As Salvage Treatment of Acute Promyelocytic Leukemia Initially Treated With All-<i>Trans</i>-Retinoic Acid: A Retrospective Analysis of the European Acute Promyelocytic Leukemia Group
Authors: S. de Botton, A. Fawaz, S. Chevret, H. Dombret, X. Thomas, M. Sanz, A. Guerci, J. San Miguel, J. de la Serna, A.M. Stoppa, O. Reman, A. Stamatoulas, M. Fey, J.Y. Cahn, J.J. Sotto, J.H. Bourhis, A. Parry, C. Chomienne, L. Degos, P. Fenaux
Journal: Journal of Clinical Oncology (2004)

To retrospectively determine the outcome of acute promyelocytic leukemia (APL) patients who underwent autologous or allogeneic stem-cell transplantation (SCT) during second complete remission.Of 122 relapsing patients included in two successive multicenter APL trials who achieved hematological second complete remission (generally after a salvage regimen of all-trans-retinoic acid [ATRA] combined with chemotherapy), 73 (60%) received allogeneic (n = 23) or autologous (n = 50) SCT.Seven-year relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS) in the autologous SCT group were 79.4%, 60.6%, and 59.8%, respectively, with a transplant-related mortality (TRM) of 6%. Of the 28 and two patients autografted with negative and positive, respectively, reverse transcriptase-polymerase chain reaction before auto SCT, three (11%) and one relapsed, respectively. In the allogeneic SCT group, 7-year RFS, EFS, and OS were 92.3%, 52.2%, and 51.8%, respectively, with 39% TRM. OS was significantly better in the autologous SCT group than in the allogeneic SCT group (P = .04), whereas RFS and EFS did not differ significantly (P = .19 and P = .11, respectively). In patients not receiving transplantation, 7-year RFS, EFS, and OS were 38%, 30.4%, and 39.5%, respectively.These retrospective data suggest that autologous SCT is very effective in APL relapsing after treatment with ATRA if performed in molecular remission. Allogeneic SCT yields few relapses, but it is associated with high TRM when performed after salvage with very intensive chemotherapy. Salvage with arsenic trioxyde, which has lower toxicity, should further improve the outcome of relapsing APL, especially before allogeneic SCT.
Buccal Mucosa Cells as <i>In vivo</i> Model to Evaluate Gefitinib Activity in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Maura Loprevite, Marcello Tiseo, Maurizio Chiaramondia, Marzia Capelletti, Cecilia Bozzetti, Beatrice Bortesi, Nadia Naldi, Rita Nizzoli, Patrizia Dadati, Annalisa Kunkl, Daniela Zennaro, Costanza Lagrasta, Nicoletta Campanini, Elena Spiritelli, Roberta Camisa, Francesco Grossi, Guido Rindi, Vittorio Franciosi, Andrea Ardizzoni
Journal: Clinical Cancer Research (2007)

To evaluate the role of pretreatment and posttreatment expression in buccal mucosa cells of signal transduction proteins activated by epidermal growth factor receptor, including phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated mitogen-activated protein kinase (p-MAPK), and phosphorylated AKT (p-AKT), in predicting gefitinib activity in advanced non-small cell lung cancer patients. Expression of the same proteins was also assessed on corresponding tissue samples for comparison. Moreover, EGFR gene mutations and copy number were analyzed.Protein expression was evaluated by standard immunocytochemistry in buccal smears, obtained by scraping immediately before and after 2 weeks of gefitinib treatment, and in the available archival tumor specimens. EGFR gene mutations were evaluated by direct sequencing and gene copy number was determined by fluorescence in situ hybridization. Data were correlated with gefitinib toxicity and objective response.Fifty-eight patients with pretreated advanced non-small cell lung cancer were enrolled and nine of these patients (15%) showed an objective response to gefitinib (including two complete responses). Toxicity (P = 0.025) and baseline p-AKT expression in buccal mucosa cells (P = 0.061) showed a potential predictive role. On the contrary, the probability of achieving an objective response was not affected by pretreatment expression of EGFR, p-EGFR, and p-MAPK, either in buccal mucosa or in tumor tissue. Responders showed a nonstatistically significant trend toward a more pronounced reduction in the expression of p-EGFR, p-MAPK, and p-AKT after gefitinib treatment. Among responders, five of six (83%) tumors showed EGFR gene mutation, whereas none of the tumors from patients with stable or progressive disease did (P < 0.001).Epithelial cells obtained from buccal mucosa may be used to assess the pharmacodynamic effect of EGFR-targeted agents, and pretreatment p-AKT expression may be a possible predictive biomarker of in vivo gefitinib activity.
Serum type III procollagen peptide concentration in cryptogenic fibrosing alveolitis and its clinical relevance.
Authors: J M Kirk, E D Bateman, P L Haslam, G J Laurent, M Turner-Warwick
Journal: Thorax (1984)

The serum concentrations of a metabolite produced during synthesis type III collagen, type III procollagen peptide (PCP), were measured in patients with cryptogenic fibrosing alveolitis, and the results were related to the course of the disease and its response to treatment. The mean PCP concentration was significantly higher for patients untreated at the time of sampling than for an age and sex matched control group (p less than 0.001). Seventeen of these patients subsequently started treatment and their response to treatment was assessed by measurement of changes in the transfer coefficient (KCO) and forced vital capacity (FVC) at six months and one year later. Those patients showing a response to treatment, indicated by an increase in the percentage predicted KCO or FVC of more than 10% one year after starting treatment, had a significantly higher mean PCP concentration (p less than 0.01 and p less than 0.001 respectively) than patients with stable or deteriorating physiological indices. When the PCP concentrations of these patients were compared with repeat measurements three to six months after the commencement of treatment 14 out of 17 showed a decrease in PCP levels. This percentage change in PCP concentrations correlated significantly with the change in the percentage predicted KCO and FVC at 12 months after the commencement of treatment (p less than 0.01). These results suggest that measurement of PCP concentrations in patients with cryptogenic fibrosing alveolitis may be useful in the assessment of response to treatment.
Independent regulation of Ca2+ entry and release from internal stores in activated B cells.
Authors: E W Gelfand, S L MacDougall, R K Cheung, S Grinstein
Journal: The Journal of Experimental Medicine (1989)

Addition of crosslinking antibody to B lymphocytes results in a rapid rise in cytoplasmic-free Ca2+ ([Ca2+]i) due to release of Ca2+ from internal stores and uptake of Ca2+ across the plasma membrane. Inositol 1,4,5-trisphosphate is believed to mediate the release of internal Ca2+ stores and has also been proposed to mediate extracellular Ca2+ entry. We have compared the properties of these two pathways for Ca2+ mobilization by dissociating the [Ca2+]i changes in ligand-activated human B cells after loading of the cells with the Ca2+ chelator BAPTA. In the present paper we show that: (a) the sustained increase in [Ca2+]i is due to increased unidirectional influx of external [Ca2+]i; (b) entry of extracellular Ca2+, but not release of internal stores, is sensitive to the transmembrane potential; and (c) entry of extracellular Ca2+, but not release of internal stores, is inhibited by increasing [Ca2+]i. These findings suggest that the permeation pathways mediating the translocation of Ca2+ across the plasma membrane and endoplasmic reticulum membrane are not identical.