tbuckley/cabot-search huggingface dataset:
Aurora-A down-regulates IkappaBα via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival
Authors: Jin-e Yao, Min Yan, Zhong Guan, Chao-bin Pan, Liang-ping Xia, Chuan-xing Li, Li-hui Wang, Zi-jie Long, Yan Zhao, Ming-wei Li, Fei-meng Zheng, Jie Xu, Dong-jun Lin, Quentin Liu
Journal: Molecular Cancer (2009)

Abstract Background The mitotic Aurora-A kinase exerts crucial functions in maintaining mitotic fidelity. As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated. Results Here, we found that Aurora-A overexpression was closely correlated with clinic stage and lymph node metastasis in tongue carcinoma. Aurora-A inhibitory VX-680 suppressed proliferation, induced apoptosis and markedly reduced migration in cancer cells. We further showed that insulin-like growth factor-1, a PI3K physiological activator, reversed VX-680-decreased cell survival and motility. Conversely, wortmannin, a PI3K inhibitor, combined with VX-680 showed a synergistic effect on inducing apoptosis and suppressing migration. In addition, Aurora-A inhibition suppressed Akt activation, and VX-680-induced apoptosis was attenuated by Myr-Akt overexpression, revealing a cross-talk between Aurora-A and PI3K pathway interacting at Akt activation. Significantly, we showed that suppression of Aurora-A decreased phosphorylated Akt and was associated with increased IkappaBα expression. By contrast, Aurora-A overexpression upregulated Akt activity and downregulated IkappaBα, these changes were accompanied by nuclear translocation of nuclear factor-κB and increased expression of its target gene Bcl-xL. Lastly, Aurora-A overexpression induced IkappaBα reduction was abrogated by suppression of Akt either chemically or genetically. Conclusion Taken together, our data established that Aurora-A, via activating Akt, stimulated nuclear factor-κB signaling pathway to promote cancer cell survival, and promised a novel combined chemotherapy targeting both Aurora-A and PI3K in cancer treatment.
In vivo studies of amylose- and ethylcellulose-coated [13C]glucose microspheres as a model for drug delivery to the colon
Authors: J.H Cummings, Snezana Milojevic, Marilyn Harding, W.A. Coward, G.R. Gibson, R. Louise Botham, S.G. Ring, E.P. Wraight, M.A. Stockham, M.C. Allwood, J.M. Newton
Journal: Journal of Controlled Release (1996)
767 HCV-RELATED STEATOSIS AND RISK OF ATHEROSCLEROSIS
Authors: R. Zampino, T. Pasquariello, A. Florio, L. Restivo, C. De Rosa, M.F. Tripodi, L. Rinaldi, A. Marrone, G. Ruggiero, L.E. Adinolfi
Journal: Journal of Hepatology (2008)
Clinical Research Should Not Be Permitted to Escape the Ethical Orbit of Clinical Care
Authors: David Steinberg
Journal: The American Journal of Bioethics (2002)

Miller and Brody’s (2002) argument supporting the use of placebo-controlled clinical trials includes statements that are disturbing, particularly their claim of an “ethically fundamental distinction between clinical research and clinical care.” Clinical research is a branch of clinical medicine that has been accorded dispensations such as the ability to use unapproved drugs and novel therapies. This license comes with obligations such as provision of a clear and detailed statement describing the research, institutional review board approval, and informed consent. Clinical investigators have not, as Miller and Brody seem to contend, been accorded broad immunity from the ethical standards of clinical practice in general. Miller and Brody quite remarkably absolve clinical investigators of responsibility for the consequences of their experiments by advising physicians to avoid “the dual roles of treating physician and investigator.” If a physician treats a patient with either an accepted or an experimental therapy, a physician-patient relationship is established that obliges the physician to care for that patient. It would be a violation of our common notion of responsibility if clinical investigators could administer an experimental therapy and then be absolved of the responsibility to manage the consequences of their intervention. This should particularly be true for clinical investigators who are likely to be using protocols and drugs less familiar to other physicians. Miller and Brody would allow physicians to accept clinical responsibility when their clinical trials pose “only slight risks”; I think they have it backward. It is even more important for a physician to care for a patient when the risks of their interventions are high.
Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls
Authors: A M Jacobi, D M Goldenberg, F Hiepe, A Radbruch, G R Burmester, T Dörner
Journal: Annals of the Rheumatic Diseases (2007)

Objective: B lymphocytes have been implicated in the pathogenesis of lupus and other autoimmune diseases, resulting in the introduction of B cell-directed therapies. Epratuzumab, a humanised anti-CD22 monoclonal antibody, is currently in clinical trials, although its effects on patients’ B cells are not completely understood. Methods: This study analysed the in vivo effect of epratuzumab on peripheral B cell subsets in 12 patients with systemic lupus erythematosus, and also addressed the in vitro effects of the drug by analysing anti-immunoglobulin-induced proliferation of isolated B cells obtained from the peripheral blood of 11 additional patients with lupus and seven normal subjects. Results: Upon treatment, a pronounced reduction of CD27 – B cells and CD22 surface expression on CD27 – B cells was observed, suggesting that these cells, which mainly comprise naïve and transitional B cells, are preferentially targeted by epratuzumab in vivo. The results of in vitro studies indicate additional regulatory effects of the drug by reducing the enhanced activation and proliferation of anti-immunoglobulin-stimulated lupus B cells after co-incubation with CD40L or CpG. Epratuzumab inhibited the proliferation of B cells from patients with systemic lupus erythematosus but not normal B cells under all culture conditions. Conclusions: Epratuzumab preferentially modulates the exaggerated activation and proliferation of B cells from patients with lupus in contrast to normal subjects, thus suggesting that epratuzumab might offer a new therapeutic option for patients with systemic lupus erythematosus, as enhanced B cell activation is a hallmark of this disease.
Case of Carbon-monoxide Poisoning with Complications
Authors: R. C. Jackson, N. V. Bunker, W. J. Elder, P. J. O'Connor
Journal: BMJ (1959)

We are now very near to being able to predict from tests in vitro whether a given sample of red cells will undergo rapid destruction if transfused to a particular patient and, if so, how rapid destruction will be, whether it will involve all or only some of the transfused red cells, whether it will be predominantly intravascular or extravascular, and, if extravascular, whether it will occur predominantly in the liver or the spleen.Further observations, particularly in patients whose serum contains "cold " specific iso-agglutinins, are needed to define still more clearly the relationship between the thermal range of an antibody in vitro and its power to bring about red-cell destruction in vivo.The more academic problem of the relatively slow destruction, in particular subjects, of transfused red cells in the absence of demonstrable antibodies still awaits solution.I wish to thank Professor A. C. Dornhorst for many helpful discussions ; Dr. W. J. Jenkins for permission to use his serological findings in the case referred to in Figs. 18 and 19; Dr. E. E. Pochin for permission to investigate a patient under his care; Miss Marie Cutbush (now Mrs. Crookston), B.Sc., for help with some of the experiments on the removal of sensitized red cells from the circulation; Miss Margaret Polley, B.Sc
Conventional heart rate variability analysis of ambulatory electrocardiographiic recording fails to predict imminent ventricular fibrillation
Authors: Tomas Vybiral, Donald H. Glaeser, Ary L. Goldberger, David R. Rigney, Kenneth R. Hess, Joseph Mietus, James E. Skinner, Marilyn Francis, Craig M. Pratt
Journal: Journal of the American College of Cardiology (1993)
Natural Resistance-Associated Macrophage Protein Is a Cellular Receptor for Sindbis Virus in Both Insect and Mammalian Hosts
Authors: Patrick P. Rose, Sheri L. Hanna, Anna Spiridigliozzi, Nattha Wannissorn, Daniel P. Beiting, Susan R. Ross, Richard W. Hardy, Shelly A. Bambina, Mark T. Heise, Sara Cherry
Journal: Cell Host & Microbe (2011)
A critical improvement of the local thermodilution method for measuring renal blood flow in man
Authors: F. MAGRINI, L. GUO-QUING
Journal: Cardiovascular Research (1982)

A new catheter with a "pig tail" shaped end has been used for renal venous blood outflow measurement by the local thermodilution method. Left and right renal blood flow were measured in nine hypertensive patients with monolateral renal artery stenosis (previously documented by selective renal angiography). Percutaneous introduction and positioning of the "pig tail" catheter in the renal veins was performed without complications. In all cases no deformities in the dilution curves due to: a) contact of the thermistor with the vessel walls; b) shifting baseline during injection; or c) variable and inhomogeneous mixing, were observed. Mean percentage variation of five consecutive renal blood flow determinations was 6% in a flow range from 154 to 718 cm3·min−1. We conclude that the use of "pig tail" catheters represents a critical improvement of the local thermodilution method for measuring renal blood flow.
Adenosine deaminase and terminal deoxynucleotidyl transferase in human lymphomas: An aid to the diagnosis and subclassification of lymphoblastic lymphomas
Authors: Paolo Vezzoni, Roberto Giardini, Roberto Lucchini, Luciano Lombardi, Maria A. Vezzoni, Carlo Besana, Libero Clerici
Journal: American Journal of Hematology (1985)

Abstract Adenosine deaminase (ADA) and terminal deoxynucleotidyl transferase (TdT) activities were determined on 97 biopsic specimens obtained from patients with non‐neoplastic diseases (12 cases), Hodgkin (30 cases), and non‐Hodgkin lymphomas (55 cases). Thirty additional cases were tested only for TdT. TdT was positive in 10 out of 13 lymphoblastic lymphomas (LL) examined and negative in all the other specimens, including the ten cases of the immunoblastic type. Levels of ADA above 350 U/mg of protein were found in 10 out of 12 LL tested, but not in any other specimen. The 3 TdT − LL had high contents of ADA. Therefore, all LL can be detected using both ADA and TdT markers. The 3 TdT − LL had a heterogeneous phenotype and their possible origin is discussed in view of the possibility that they constitute a rare entity distinct from the more common TdT + LL. Very low levels of ADA (below 100 U/mg of protein) were found in chronic lymphocytic leukemia and immunocytoma, and in Burkitt's lymphoma. In other B‐cell non‐Hodgkin lymphomas, intermediate values between 100 and 350 U were often found, and this finding could be relevant to the different cellular origin of the various B‐cell neoplasias. We conclude that ADA distribution in solid lymphoid tumors reflects the cellular origin of these neoplasias. Adenosine deaminase alone and in combination with TdT can be useful in the diagnosis and classification of childhood lymphomas in which the immature hystotypes predominate.
Ventriculo-atrial Conduction in Man
Authors: BRUCE N. GOLDREYER, J. THOMAS BIGGER
Journal: Circulation (1970)

Transvenous electrodes were placed in the right atrium and ventricle of 50 patients with heart disease and arrhythmias. The ventricles were paced at several rates, each in excess of the sino-atrial rate. An atrial electrogram and surface electrocardiogram were recorded simultaneously in each patient; utilizing strict criteria, the incidence with which 1:1 ventriculo-atrial conduction (VAC) could be elicited in these patients was assessed. These patients were divided into two groups-26 patients with normal A-V conduction comprised group 1, and 24 patients with prolonged A-V conduction, group 2. VAC was demonstrated in 89% of group 1 patients but in only 8% of the group 2 patients. The difference in the incidence of 1:1 VAC between the two groups was statistically significant ( P &lt; 0.01). The presence or absence of 1:1 VAC could not be related to type of heart disease, medication, presence of acute myocardial infarction, or presence of intraventricular conduction defect. Altering the paced ventricular rate or introducing stimulated ventricular premature depolarization in group 1 patients could produce any degree of VAC impairment. During such maneuvers, ventricular reciprocal beats (ventricular echoes) and ventricular reciprocal rhythms were observed.
A Totally Automated Psychological Test
Authors: Wendell M. Swenson
Journal: JAMA (1965)

For decades the general medical practitioner has been aware of the large psychiatric or psychological component in his medical patients. What the physician specifically lacks, however, is a fund of patient-given information necessary for his prober evaluation of emotional conflict and possibly of major psychological problems. Usually this kind of information is available only to the psychiatric specialties, and the physician or internist has neither the time nor the inclination to obtain or organize the information necessary for the evaluation of these problems. An attempt to meet this need has been made.<sup>1</sup> No doubt one of the most valuable structured personality inventories available today is the Minnesota Multiphasic Personality Inventory<sup>2</sup>commonly identified as the MMPI. It embodies a series of 550 behavioral descriptive statements to which the patient responds true or false. These statements are grouped into several general categories for each of the basic scales. Responses of
A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma
Authors: Oliver Patschan, Gottfrid Sjödahl, Gunilla Chebil, Kristina Lövgren, Martin Lauss, Sigurdur Gudjonsson, Petter Kollberg, Pontus Eriksson, Mattias Aine, Wiking Månsson, Mårten Fernö, Fredrik Liedberg, Mattias Höglund
Journal: European Urology (2015)
The Metrics of Clinical Trials
Authors: James Wright, Lee Fairclough, Janet Manzo, Lynda Phippard, Bobbi Smuck, Joanne Lacourciere
Journal: Journal of Clinical Oncology (2005)

suppurative superinfection.Our approach to management was two-fold: In addition to a 5-day course of oral clindamycin (600 mg twice daily), the fistula was rinsed twice a day with 5 mL of a Eucalyptus-based oil mixture (KielMix-PT 70; Klonemax, Central Tilba, Australia).After 3 days, the patient's malodour had completely resolved.The patient was discharged home after 14 days.Oil therapy was continued postdischarge, and administered daily by his wife, a former nurse.After 2 and a half weeks, clinical signs of superinfection in terms of inflammation and purulence were markedly reduced.The fistula appeared clean, and there was evidence of healing by secondary intention: a layer of fibrin had formed, deep in the fistula.After 6 weeks of the essential oil regimen and no further antibiotics, the fistula had completely closed.This is not the usual course of events for ulcers associated with cancers of the head and neck.The oil therapy did not retard the growth of the tumor, and by the eighth week it had grown along the path of the former fistula to the skin surface.Despite this, the offensive smell that had prompted his presentation to the emergency department did not recur.His quality of life had been improved by the use of the essential oils, and he was able to live at home with his family for the next 10 weeks until he died.We have now treated more than 30 patients with a similar regimen of topical essential oils.Adverse effects are uncommon and are usually limited to minor irritation at the time of application.The beneficial effects, however, have been quite pronounced.We are in the process of planning a randomized controlled trial to confirm our observations.
Abraham Lincoln and the Marfan Syndrome
Authors: H. Schwartz
Journal: JAMA (1964)

The Marfan syndrome was found in a male descendant of Mordecai Lincoln II, great-great-grandfather of Abraham Lincoln. The common ancestry of the patient and the 16th president appears to establish genealogically that Lincoln's unusual morphological characteristics were manifestations of the genetically determined arrangement of connective tissue described by Marfan in 1896.
P138 Baseline Hypoxemia Predicts Survival in Patients with Idiopathic Pulmonary Arterial Hypertension Without Patent Foramen Ovale
Authors: A Nair, J Fuller, R Crackett, M Day, J Lordan, A Fisher, P Corris
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> The relevance of hypoxemia in patients with Idiopathic pulmonary arterial hypertension (IPAH) without Patent Foramen Ovale (PFO) on haemodynamics and survival is not well described. The aim of this study is to ascertain the severity and prevalence of hypoxemia in patients with IPAH without PFO, and its impact on survival. <h3>Methods</h3> This is a single centre registry evaluation from 2001–2010 of patients attending the National Pulmonary Vascular Treatment Centre for Northern England. Outcomes were prospectively recorded on database following comprehensive assessment and confirmation with right heart catheterisation. PFO was excluded using bubble contrast ECHO. Data on arterial blood gas (ABG), lung function and radiology were obtained from case notes/hospital reporting systems. Patients initiated on targeted therapy were followed up at 3–4 month intervals. <h3>Results</h3> ABG data was available for a cohort of 44 IPAH patients. 28(58%) were women. Mean age (SD) was 55.6(16.6) years, mean (SE) for Mean PAP 47(1.7) mm Hg, CI 2.18(0.09) L/min/m2, 6MWD 266(22) metres, PaO2 9.04(0.25) kPa, SPO2% 93(0.3), FEV1% 81.1(2.8), DLCO% 61.4(3.4). Mild Hypoxemia was seen in7(16%), Moderate Hypoxemia in 26(59%), Severe Hypoxemia in 11 (25%) patients respectively. There were significant differences in survival between groups (logrank P value 0.0012, Figure 1). Mean survival (95% CI) in mild, moderate and severe hypoxemia groups were 12.3 years (9.1 to 15.4), 6.84(4.8 to 8.8), and 2.8(1.6 to 3.9) years respectively. There were no correlations between PaO2 and haemodynamic measurements (RAP/CI/PVR)/FEV1/FC. A modest correlation r. 32 was observed between PaO2 and 6MWD, (P0.04). <h3>Conclusion</h3> Baseline Hypoxemia is an independent predictor of survival whilst on targeted therapy and moderate hypoxemia is prevalent in the absence of PFO/lung disease in IPAH.
Second Cancers in patients With Chronic Lymphocytic Leukemia
Authors: L. B. Travis, R. E. Curtis, B. F. Hankey, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1992)

Reports to date have provided widely divergent estimates of the risk of second malignant neoplasms in patients with chronic lymphocytic leukemia (CLL), ranging from cancer deficits to excesses of twofold to threefold.Our purpose was to estimate the risk of second primary cancers following CLL, utilizing population-based tumor registries, and to determine whether site-specific excesses might be associated with type of initial treatment for CLL.We analyzed data for 9456 patients diagnosed with CLL as a first primary cancer between 1973 and 1988, who were reported to one of nine tumor registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and who survived 2 or more months. SEER files were searched for invasive primary malignancies that developed at least 2 months after the initial CLL diagnosis.Compared with the general population, CLL patients demonstrated a significantly increased risk of developing all second cancers (840 observed; observed-to-expected ratio [O/E] = 1.28; 95% confidence interval [CI] = 1.19-1.37). Significant excesses were noted for cancers of the lung (O/E = 1.90), brain (O/E = 1.98), and eye (intraocular melanoma) (O/E = 3.97) as well as malignant melanoma (O/E = 2.79) and Hodgkin's disease (O/E = 7.69). Cancer risk, which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis.CLL patients are at a significantly increased risk of developing a second malignant neoplasm. The pattern of cancer excesses suggests a susceptibility state permitting the development of selected second malignancies in patients with CLL, perhaps because of shared etiologic factors, immunologic impairment, and/or other influences. Although our results do not suggest a strong treatment effect, more detailed studies of second tumors in CLL are needed to investigate the role of radiation therapy and chemotherapy.
Sézary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3
Authors: N Booken, A Gratchev, J Utikal, C Weiß, X Yu, M Qadoumi, M Schmuth, N Sepp, D Nashan, K Rass, T Tüting, C Assaf, E Dippel, R Stadler, C-D Klemke, S Goerdt
Journal: Leukemia (2007)
An Atlas of Hemodynamics of the Cardiovascular System.
Authors: Harry A. Bliss
Journal: JAMA (1963)

Modem devices for detecting pressure and sound in the cardiovascular system have added much to our understanding of normal and abnormal heart action. In this volume the authors describe their own observations of these phenomena, mainly in dogs with experimental valvular heart disease. The effects of acute valvular lesions on pressure pulses simultaneously recorded from several cardiac chambers occupies most of the first half of the book, while other topics, principally intracardiac pressure pulses in experimentally produced arrhythmias, are dealt with in the remaining pages. Intracardiac and external phonocardiograms frequently are related to events in the pressure tracings. A few angiocardiograms also are included. The illustrations carry the burden of the book's message. Each takes up a full page opposite a descriptive block of text in which the causes, hemodynamic consequences, clinical manifestations, and therapy of the lesions are discussed. Since the pressure recordings were obtained with manometric systems free
RV FRACTIONAL AREA CHANGE AT 6 MONTHS BUT NOT AT PRE-IMPLANT IS ASSOCIATED WITH LATE INDICES OF FUNCTIONAL CAPACITY AND RENAL FUNCTION: A CASE FOR THE IMPORTANCE OF LATE RV DYSFUNCTION IN LONG TERM MCS
Authors: Jesus Rame, Edo Birati, Vimal Ramjee, Eva Laverty-Wilson, Ted Plappert, Joseph Donnelly, Joyce Wald, Pavan Atluri, Y. Joseph Woo, Michael Acker, James Kirkpatrick
Journal: Journal of the American College of Cardiology (2014)