tbuckley/cabot-search huggingface dataset:
Characterization of prostaglandin E2 receptors and their role in PGE2-induced VEGF expression in prostate cancer cells
Authors: Xingya Wang, Russell D. Klein
Journal: Cancer Research (2005)

756  There is strong evidence that prostaglandins (PG) synthesized by cyclooxygenase enzymes (COX-1 and COX-2) play a significant role in the development of cancer. In prostate cancers, PGs have been reported to be elevated, and the use of COX inhibitors (primarily aspirin) have been associated with a decreased risk of developing prostate cancer. However, COX inhibitors are criticized for causing gastrointestinal side effects and other potential risks. PGE2 is the most abundant PG in the prostate and has been shown to induce expression of angiogenic factors including VEGF. Thus, inhibition of downstream effectors of PGE2, such as PGE2 membrane receptors (EP1-4), may be an attractive new strategy for prostate cancer prevention and therapy. The objective of the current study was to characterize EP receptor expression in seven human prostate cell lines and the TRAMP mouse model of prostate cancer and to identify which EP receptors are involved in PGE2-induced VEGF synthesis. EP1 is not detectable in any of the seven human prostate cell lines (PWR-1E, RWPE-1, RWPE-2, 22RV1, PC-3, LNCaP and DU145) or in TRAMP prostate tissues by immunoblotting. EP2 is expressed in all of the cell lines with different intensity by immunoblotting. Interestingly, the non-tumorigenic RWPE-1 cell line expresses significant lower EP2 than the tumorigenic RWPE-2 cells. DU145 and LNCaP have much higher EP2 expression compared to PC-3 cells. In addition, we detected high expression of EP2 by immunoblotting and IHC staining in TRAMP prostate tissue. The expression of EP3 was only detected in PC-3, LNCaP and DU145 cells. EP4 is expressed in all the cell lines with PC-3, 22RV1 and DU145 having the highest level of EP4 compared to other cell lines. Correlating with their EP2 expression, but not other receptors, the basal level of VEGF secreted in 24 hrs is high in DU145 (1653.4pg/ml) and LNCaP (825.8pg/ml) cells, but very low in PC-3 cells (45.1pg/ml). RWPE-2 cells, which have higher EP2 than RWPE-1 cells, secreted almost 5 fold more VEGF compared to RWPE-1 cells (212.3pg/ml vs. 45.6pg/ml). In addition, treatment of these five cell lines with PGE2 (0, 1nM, 10nM, 100nM, 1μM, 10μM) dose-dependently stimulated VEGF secretion. Interestingly, PC-3, which has the lowest endogenous VEGF, had the greatest response to PGE2 stimulation, with an increase of VEGF of 29% (1nM), 50% (10nM), 65% (100nM), 82% (1μM) and 131% (10μM). Cay 10399, an EP2 agonist, also dose-dependently up-regulated VEGF expression in PC-3 cells. We conclude that PGE2 stimulates VEGF production in prostate epithelial cells, and this is most likely mediated by EP2 and possibly EP4 receptors. Supported by KO7 CA091865 from the NCI.
Recent Advances: Clinical pharmacology and therapeutics
Authors: A. Breckenridge
Journal: BMJ (1995)

so, in close cooperation with the medical team, as the minor is at risk of appreciable harm if treatment or feeding, or both, are not enforced.We thank the families and young people involved.We also thank the solicitors for the hospital and those from the London Borough of Camden's legal team working for the social services department for their help in managing the cases described and advising on legal points in the paper.
A guide to science reading.
Authors: Hilary J. Deason
Journal: JAMA (1963)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Renal Function, Congestive Heart Failure, and Amino-Terminal Pro-Brain Natriuretic Peptide Measurement
Authors: Saif Anwaruddin, Donald M. Lloyd-Jones, Aaron Baggish, Annabel Chen, Daniel Krauser, Roderick Tung, Claudia Chae, James L. Januzzi
Journal: Journal of the American College of Cardiology (2005)
Abstract 2780: A First-in-Class Oligonucleotide Drug-Antidote Pair Efficiently Modulates Factor IXa Activity in Human Subjects - A Nascent Platform for Antidote-Controlled Periprocedural Anticoagulation
Authors: Mark Y Chan, Mauricio G Cohen, Christopher P Rusconi, John H Alexander, Shelley K Myles, Laura G Aberle, Min Lin, Chiara Melloni, Ross M Tonkens, Robert A Harrington, Richard C Becker
Journal: Circulation (2007)

Background: Safe and active reversibility of anticoagulation is highly desirable. Factor IXa, critical for rapid thrombin generation on platelet surfaces, is a novel target for regulating coagulation. The REG1 System comprises RB006 (drug) and RB007 (antidote). RB006, a ribonucleic acid aptamer, selectively binds and inhibits IXa. RB007, the complementary oligonucleotide antidote, binds to RB006 by Watson-Crick base pairing, neutralizing its anti-factor IXa activity. Methods: To explore the feasiblity of testing the REG1 system in catheter-based intervention trials, we analyzed data from 2 randomized dose-escalation studies of REG1: phase 1a with 84 healthy subjects and phase 1b with 50 patients with stable coronary artery disease taking aspirin and/or clopidogrel. Results: An intravenous (IV) bolus of RB006 produced a similar dose-dependent activated partial thromboplastin time (aPTT) increase in both populations; a weight-adjusted dose of 1mg/kg RB006 consistently achieved 100% factor IXa inhibition (figure 1 ), a level effectively eliminating artifical surface thrombosis in animal models. IV bolus RB007 in a 2:1 antidote:drug ratio reversed the aPTT to &lt;10% above the upper limit of normal within a median of 1 min (IQR 1–2), with no rebound increase up to 7 days. Despite dual antiplatelet use in 19 subjects, no major bleeding or other serious adverse events occurred. Conclusions: These exploratory data support the safe regulation of coagulation with a factor IXa-specific drug-antidote system. The pharmacodynamic response elicted by a 1mg/kg RB006 dose and 2:1 antidote:drug ratio appears suitable for catheter-based intervention studies. Figure 1. Relative APTT and % Factor IXa inhibition versus RB008 Dose (mg/kg)
Abstract 19614: Formation of 3D Cardiac Tissues From Human Pluripotent Stem Cells Using a Highly Reproducible, One-Step Encapsulation Approach
Authors: Petra Kerscher, Alexander J Hodge, Joonyul Kim, Irene C Turnbull, Dror Seliktar, Christopher J Easley, Kevin D Costa, Elizabeth A Lipke
Journal: Circulation (2014)

Human induced pluripotent stem cells (hiPSCs) provide great potential for improving drug testing, facilitating myocardial repair, and investigating heart development. Currently, SC derived cardiomyocytes (CMs) are pre-differentiated from hiPSCs, dissociated, and combined with a biomaterial to form 3D cardiac tissues. This demands additional cell-handling, results in a high level of cell loss, and disrupts pre-existing cell-cell junctions. Here we describe a one-step approach to directly encapsulate and differentiate hiPSCs into 3D cardiac tissues. HiPSCs were combined with poly(ethylene glycol)-fibrinogen and photocrosslinked to form 200 μm thick tissues. Encapsulated hiPSCs (day -3) were cultured in their pluripotent state for three days where they proliferated. On day 0, cardiac differentiation was initiated. Tissues showed areas of contractions starting on day 7, resulting in synchronously contracting tissues which retained their function over three months. Sarcomeric α-actinin and gap junction protein connexin 43 (Cx43) were expressed by day 10; aligned sarcomeres (day 30) and mature gap junctions (Fig. 1a) developed over time. CM maturation increased significantly from day 10 to day 30, as quantified by the ratio of β over α myosin heavy chain gene expression; Cx43 expression increased from 0.5±0.3 (day 20) to 1.0±0.1 (day 30). Additionally, day 15 CMs showed 1:1 correspondence to electrical stimuli of up to 2 Hz. Finally, TEM of day 130 tissues showed structural features of mature CMs, including Z-bands, T-tubules, and intercalated discs (Fig. 1b). In summary, this one-step encapsulation approach successfully produces highly reproducible 3D cardiac tissues with mature and functional features. Furthermore, these physiologically relevant CMs can be used to produce printed microislands, macrotissues, spheroids, or single CMs, based on the desired downstream application.

Fig. 1. 3D encapsulation of hiPSCs produce functional cardiac tissues.

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Targeting mutant nucleophosmin (NPM)1 induces differentiation and loss of clonogenic survival of human AML cells.
Authors: Bryan Herger, Pravina Fernandez, Warren Fiskus, Rekha Rao, Kapil Bhalla
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4084 

NPM1 is a nucleolar phosphoprotein that functions as a molecular chaperone for both proteins and nucleic acids and is capable of histone and nucleosome assembly. NPM1 is involved in regulating the activity of p53 and p14ARF, such that cells lacking NPM1 show decreased p14ARF. NPM1 maps to 5q35 locus, which is often deleted in myelodysplastic syndrome (MDS). NPM1-/- mice are embryonically lethal, while NPM1+/- mice develop hematologic syndrome with features of human MDS. NPM1 shuttles between nucleus and cytoplasm, but when mutated, it is aberrantly localized to the cytoplasm in 35% of patients with AML. Mutant (m) NPM1 contains a 4-base insert that results in a frame-shifted mutant protein with extra C-terminal residues that encode a nuclear export signal (NES), causing mNPM1 to remain in the cytoplasm. The role of the mutant, cytosolic NPM1 in the pathogenesis of AML remains to be fully elucidated. First, in the present studies, among 15 AML patient samples evaluated by RT-PCR analyses specific for mutant sequences, 4 had FLT3 internal tandem duplications (ITD), of which 2 had mNPM1. This was determined to be cytosolic by sub-cellular fractionation and immunoblot analysis and by immunofluorescent localization. As compared to control siRNA treatment, knockdown of NPM1 by siRNA specific to NPM1 (> 75%) over 72 hours induced p21 levels, cell-cycle G1 phase accumulation, and significant inhibition of clonogenic survival only of OCI-AML3 (p < 0.004) (which have mutant cytosolic and unmutated, WT, nuclear NPM1) but not of HL-60 cells (which only have WT NPM1). NPM1 knockdown by siRNA also induced differentiation in approximately 50% of OCI-AML3 but not HL-60 cells, as determined by Wright staining and morphologic evaluation. In contrast, ATRA (1.0 uM) and DMSO (1.2%) induced differentiation of both cell types. OCI-AML3 cells co-express HOXA9 and MEIS1 proteins, which are known to be leukemogenic in mouse myeloid cells. MEIS1 is also known to transactivate FLT3 tyrosine kinase in AML progenitor cells. Notably, NPM1 knockdown by siRNA depleted HOXA9 and MEIS1 mRNA and protein expressions in OCI-AML3 cells. HL-60 cells do not express either protein. NPM1 siRNA did not induce significant apoptosis or loss of cell viability determined by trypan blue uptake assay. Treatment of OCI-AML3 cells with leptomycin B (5 nM for 48 hours), an inhibitor of the NES receptor CRM1/exportin, shifted the localization of mNPM1 from the cytosol to nucleus and depleted the levels of HOXA9 in OCI-AML3 cells. Mutant nucleophosmin could prove to be a useful therapeutic target in certain AML cases. Collectively, these findings suggest that attenuating mNPM1 levels or reversing the aberrant cytosolic localization on mNPM1 may be a promising anti-AML treatment strategy, especially for AML that co-express FLT3-ITD and mNPM1.
The diagnosis of latent tuberculosis infection in children with new immunologic tests
Authors: Anna Starshinova, Irina Dovgaliuk, Natalia Korneva, Olga Yakunova, Piotr Yablonskiy
Journal: European Respiratory Journal (2013)

It is commonly known that due to widely used vaccination by BCG the diagnostic value of tuberculin skin test (TT) is not high in the assessment of latent tuberculosis infection in children as BCG vaccination modifies susceptibility to tuberculin. The implementation of new immunological tests allows revealing latent tuberculosis in children more efficiently.

Objectives: to diagnose latent tuberculosis infection in children with different susceptibility to TT with new immunological tests (Diaskintest ® and QuantiFERON-TB Gold).

Materials and methods: at children department of Saint-Petersburg Institute of Phthisiopulmonology 77 patients aged from 3 to 14 years with positive TT were examined during 2010-2012. All children were vaccinated by BCG. Diagnostic complex included: Diaskintest ® (DST) – immunological skin test, QuantiFERON-TB Gold (QFT-G), and multislice computer tomography (MCT).

Results: examined children were divided into groups by different susceptibility to tuberculin by TT: in 27.3% (21) - low reaction in TT (≤ 10MM) (I group), in 63.6% (49) – moderate reaction in TT (10-15 MM) (II group), and in 9.1% high reaction (>15MM) (III group). In none of the cases specific tuberculosis changes in intrathoracic lymphatic nodes and lung tissue were observed by MCT. DST positive test was observed: in the I group in 19.1% (4), in II – 26.5% (13), in III – 71.4% (5). Results of QFT-G were similar to DST: in I group - was in 28.6% (6), in II – 24.5% (12), in III – 85.7% (6).

Conclusions: Thus both immunological tests are recommended in diagnostic complex of latent tuberculosis infection in children.
Abstract P2-01-14: Pre-operative axillary staging results in over-treatment in some breast cancer patients
Authors: Andrew Pieri, Henry Cain, Sebastian Aspinall
Journal: Cancer Research (2015)

Abstract Introduction Following a diagnosis of breast cancer, pre-operative ultrasound staging of the axilla is recommended. Patients found to have metastatic disease on biopsy or FNA can proceed directly to axillary clearance (ALNC) at the time of their breast tumour excision. However, although ultrasound staging is a sensitive test to detect axillary disease, it does not differentiate between low and high volume nodal metastasis. Recent evidence suggests that, in selected patients with low volume axillary disease following SLNB, completion ALNC may be safely omitted. This has been reflected in the recently updated ASCO guidelines. In light of this current trend towards axillary conservation, some patients undergoing ALNC after positive axillary staging may be over-treated. The aims of this study is to establish the nodal burden of patients undergoing ALNC following positive axillary staging and to compare the nodal burden of those patients with those undergoing completion ALNC after a positive SLNB. Methods Data was collected prospectively over 12 months from nine hospitals within the North of England Cancer Network. Age, tumour characteristics, breast operation, axillary staging results, axillary operation(s) and nodal results were recorded. Results A total of 1010 patients with breast cancer underwent pre-operative axillary staging. 215 patients (21%) had an ALNC. Of these, 115 (53%) cases underwent a primary ALNC after positive staging. The remaining 100 (47%) patients had a completion ALNC following a positive SLNB. The nodal burden for patients undergoing ALNC is shown in the table below: Total number of positive nodesALNC after positive stagingALNC after positive SLNB n patients% patientsn patients% patients087001322847472131124243121011114111044≥539341414Totals115 100 Analysis of the data revealed that tumour size was a significant predictor of low volume axillary disease (i.e. &amp;lt;3 nodes positive) [p=0.02, Mann-Whitney test]. Conclusion In this study, 46% of patients undergoing ALNC after positive staging had low volume disease (2 or less positive nodes). In the context of recent evidence if these patients had undergone a SLNB following the positive pre-operative staging they may have avoided a completion ALNC. This study demonstrates tumour size to be a significant predictor of low volume axillary disease and thus may be an important factor to consider alongside pre-operative staging when selecting patients who may be better managed by a SLNB rather than proceeding directly to ALNC. Citation Format: Andrew Pieri, Henry Cain, Sebastian Aspinall. Pre-operative axillary staging results in over-treatment in some breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-14.
P0387 : Identification of optimal cut-offs in alpha-fetoprotein and the “AFP Score” to maximise the accuracy of selection of liver transplant candidates with hepatocellular carcinoma
Authors: I.A. Rowe, E. Tsochatzis, M. Shah, D. Haldar, D. Houlihan, S. Davies, E. Godfrey, S. Shetty, J. O’Beirne, H. Mergental, C. Duvoux, A. Burroughs, M. Hoare, T. Shah
Journal: Journal of Hepatology (2015)
Understanding liver immunology using intravital microscopy
Authors: Pedro Elias Marques, André Gustavo Oliveira, Lynne Chang, Heitor Affonso Paula-Neto, Gustavo Batista Menezes
Journal: Journal of Hepatology (2015)

The liver has come a long way since it was considered only a metabolic organ attached to the gastrointestinal tract. The simultaneous ascension of immunology and intravital microscopy evidenced the liver as a central axis in the immune system, controlling immune responses to local and systemic agents as well as disease tolerance. The multiple hepatic cell populations are organized in a vascular environment that promotes intimate cellular interactions, including initiation of innate and adaptive immune responses, rapid leukocyte recruitment, pathogen clearance and production of a variety of immune mediators. In this review, we focus on the advances in liver immunology supported by intravital microscopy in diseases such as isquemia/reperfusion, acute liver injury and infections.
Abstract 14725: Effect of SAR236553/REGN727 Fully Human Monoclonal Anti-Proprotein Convertase Subtilisin/Kexin Type 9 Antibody on Plasma Lipoprotein(a) Concentrations: Pooled Analysis from Three Phase 2 Studies (NCT:01266876; 01288469; 01288443)
Authors: Daniel Gaudet, Dean Kereiakes, James McKenney, Eli Roth, Corinne Hanotin, Dan Gipe, Yunling Du, Anne-Catherine Ferrand, Henry Ginsberg, Evan Stein
Journal: Circulation (2012)

Background: Lipoprotein (a) [Lp(a)], an LDL-like lipoprotein with apolipoprotein (a) covalently bound to the existing apoB protein, increases the risk of CV disease. Only apheresis and high- dose n...
Abstract 1534: Diabetes Mellitus Is An Independent Predictor Of Mortality In Defibrillator Recipients
Authors: Carol Chen-Scarabelli, Tiziano M Scarabelli
Journal: Circulation (2007)

Background: Previous studies have shown an increased morbidity and mortality risk in patients with diabetes mellitus (DM) undergoing percutaneous coronary interventions and cardiac surgery. However, the impact of DM on mortality in patients with implantable cardioverter defibrillators (ICDs) is unknown. Aim: to investigate whether DM was associated with increased mortality risk in patients with ICDs Methods: A retrospective review of all ICD patients followed within a consecutive 2.5 year period was performed. Baseline characteristics and mortality data were compared between DM and non-DM patients. Mann Whitney test was used to analyze the differences between the means, and multivariate logistic regression analysis was performed to identify independent predictors of mortality. Results: A total of 336 patients with ICDs (including 141 patients with DM and 195 without DM) were studied. The mean age was 66.8 ± 9.6 years in the overall population, with no significant difference in baseline characteristics between the 2 groups, except for beta-blocker therapy, creatinine, and estimated glomerular infiltration rate (EGFR). Use of beta-blockers was greater in the non-DM group (92.8% vs 84.4%, p=0.02). Renal function was worse in the DM group, as documented by a higher serum creatinine (1.6 ± 0.8 mg/dl in DM vs 1.38 ± 0.74 mg/dl in non-DM, p = 0.003) and a lower EGFR (55.9 ± 22.9 ml/min/1.73m 2 vs 63.5 ± 19.9 ml/min/1.73m 2 , p=0.0005). Although the incidence of VT was not significantly different between the two groups, there was a significantly higher mortality in the DM group (27.7% vs 11.3% in non-DM, p=0.0002). On multivariate stepwise logistic regression analysis, DM was a significant independent predictor of mortality (OR 2.38, 95% CI 1.3– 4.36, p =0.005). Conclusion: DM is an independent predictor of mortality in ICD patients. Prevention of DM, as well as early diagnosis and intervention, should be emphasized in order to reduce the growing epidemic of type 2 DM and its associated complications.
Abstract 17445: Transmurally Differentiated Measurements of Myocardial ATP Hydrolysis Rate in Vivo
Authors: Albert Jang, Weina Cui, Pengyuan Zhang, Jianyi Zhang
Journal: Circulation (2014)

Difficulty in measuring myocardial Pi has been a major barrier in elucidating the speculation that decreased reserve of myocardial ATP turnover rate contributes to the progression of LV, a subject still of much debate. Recently, a novel method of extracting the ATP hydrolysis rate forgoing Pi measurement was introduced (Xiong et al, Circ 2013). This study is an extension to compare the transmural distribution of forward creatine kinase (CK) reaction (kPCr→ATP) and ATP turnover rate (kATP→Pi) in the LV myocardium of normal swine (N = 10). Bioenergetics was measured utilizing one-dimension chemical shift imaging (1D-CSI) magnetic resonance 31P spectroscopy (MRS) at 9.4T. Three sets of magnetization saturation (MST) measurements; 1D-CSI, 1D-CSI with ATP saturation and 1D-CSI with PCr-Pi double saturation (FOV 4cm, nPE = 17, nt = 12), were acquired. The kPCr→ATP and kATP→Pi of the epi and endo layers are given by: kPCr→ATP = (Mc,PCr/Ms,PCr - 1)/T1,PCrnom kATP→Pi = (Mc,ATP/Ms,ATP - 1)/T1,ATPnom - Mo,ATP/Mo,ATP...
The firing of Brother George
Authors: R. Smith
Journal: BMJ (1999)

News p 213 

The American Medical Association damaged itself and medical journals when last week it sacked George Lundberg, the editor of its journal JAMA . Lundberg, who had edited JAMA for 17years, was sacked for fast tracking publication of a study showing that many American college students do not think of oral sex as “having sex.” The study, in the issue of 20January, was fast tracked because of its relevance …
A European survey of diagnostic methods and testing protocols for Clostridium difficile
Authors: F. Barbut, M. Delmée, J.S. Brazier, J.C. Petit, I.R. Poxton, M. Rupnik, V. Lalande, C. Schneider, P. Mastrantonio, R. Alonso, E. Kuipjer, M. Tvede
Journal: Clinical Microbiology and Infection (2003)