tbuckley/cabot-search huggingface dataset:
Autocrine/Paracrine Platelet-Derived Growth Factor Regulates Proliferation of Neural Progenitor Cells
Authors: Anna Erlandsson, Karin Brännvall, Sigrun Gustafsdottir, Bengt Westermark, Karin Forsberg-Nilsson
Journal: Cancer Research (2006)

Abstract Growth factors play an important role in regulating neural stem cell proliferation and differentiation. This study shows that platelet-derived growth factor (PDGF) induces a partial differentiation of neural stem/progenitor cells (NSPCs) in the absence of other mitogens in vitro. NSPCs thus acquire an immature morphology and display markers for both neurons and glia. In addition, these cells do not readily mature in the absence of further stimuli. When NSPC cultures treated with PDGF were exposed to additional differentiation factors, however, the differentiation proceeded into neurons, astrocytes, and oligodendrocytes. We find that NSPC cultures are endowed with an endogenous PDGF-BB production. The PDGF-BB expression peaks during early differentiation and is present both in cell lysates and in conditioned medium, allowing for autocrine as well as paracrine signaling. When the NSPC-derived PDGF was inhibited, progenitor cell numbers decreased, showing that PDGF is involved in NSPC expansion. Addition of a PDGF receptor (PDGFR) inhibitor resulted in a more rapid differentiation. Neurons and oligodendrocytes appeared earlier and had more elaborate processes than in control cultures where endogenous PDGFR signaling was not blocked. Our observations point to PDGF as an inducer of partial differentiation of NSPC that also sustains progenitor cell division. Such an intermediate stage in stem cell differentiation is of relevance for the understanding of brain tumor development because autocrine PDGF stimulation is believed to drive malignant conversion of central nervous system progenitor cells. (Cancer Res 2006; 66(16): 8042-8)
Combination of malaria vector control interventions in pyrethroid resistance area in Benin: a cluster randomised controlled trial
Authors: Vincent Corbel, Martin Akogbeto, Georgia B Damien, Armel Djenontin, Fabrice Chandre, Christophe Rogier, Nicolas Moiroux, Joseph Chabi, Bio Banganna, Gil G Padonou, Marie-Claire Henry
Journal: The Lancet Infectious Diseases (2012)
Rhinoviruses delayed the circulation of the pandemic influenza A (H1N1) 2009 virus in France
Authors: J.S. Casalegno, M. Ottmann, M. Bouscambert Duchamp, V. Escuret, G. Billaud, E. Frobert, F. Morfin, B. Lina
Journal: Clinical Microbiology and Infection (2010)
Reversal of DNA hypomethylation by folic acid supplements: possible role in colorectal cancer prevention
Authors: J C Mathers
Journal: Gut (2005)

Low folate intake may predispose to a greater risk of colorectal cancer

The deranged gene expression that is causal for colorectal cancer (CRC) development results from unrepaired genomic damage which accumulates in successive generations of mucosal cells and which provides the neoplasm with a growth and/or survival advantage. Such damage includes disabling mutations in tumour suppressor (TS) genes and facilitates inappropriate expression of oncogenes. Approximately 25 years ago, evidence began to appear that changes in methylation status of DNA might be responsible for changes in gene expression. The potential importance of aberrant DNA methylation in tumorigenesis was signalled when, on 6 January 1983, Nature carried an article by Feinberg and Vogelstein1 reporting the first evidence of hypomethylation of some genes in tumours compared with “normal” tissue from the same individuals. That same year, Gama-Sosa and colleagues2 used high performance liquid chromatography to demonstrate that metastatic tumours had a significantly lower content of 5-methylcytosine than did benign neoplasms or normal tissues. Somewhat surprisingly, site specific hypermethylation of particular genes, including the classical TS the retinoblastoma gene, was observed a few years later (see Feinberg and Tycko3 for an excellent review). It is now clear that global genomic hypomethylation and hypermethylation of specific genes coexist in the same tumours but whether the genesis of the two phenomena is related remains uncertain.

Laird4 has argued that cancer may be as much a disease of misdirected epigenetics as it is of genetic mutations. Epigenetics describes non-coding changes to the genome which are transmitted through mitosis and alter gene expression. Although changes in other epigenetic markings, especially in post translational modifications of histones, are likely to be of considerable significance in tumour pathogenesis, much of the work to date has focussed on DNA methylation. Approximately 1% of DNA bases in the …
Identification of a Met-Binding Peptide from a Phage Display Library
Authors: Ping Zhao, Tessa Grabinski, Chongfeng Gao, R. Scot Skinner, Troy Giambernardi, Yanli Su, Eric Hudson, James Resau, Milton Gross, George F. Vande Woude, Rick Hay, Brian Cao
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Aberrant c-Met expression has been implicated in most types of human cancer. We are developing Met-directed imaging and therapeutic agents. Experimental Design: To seek peptides that bind specifically to receptor Met, the Met-expressing cell lines S114 and SK-LMS-1 were used for biopanning with a random peptide phage display library. Competition ELISA, fluorescence-activated cell sorting analysis, an internalization assay, and a cell proliferation assay were used to characterize a Met-binding peptide in vitro. To evaluate the utility of the peptide as a diagnostic agent in vivo, 125I-labeled peptide was injected i.v. into nude mice bearing s.c. xenografts of the Met-expressing and hepatocyte growth factor (HGF)/scatter factor–expressing SK-LMS-1/HGF, and total body scintigrams were obtained between 1 and 24 h postinjection. Results: One Met-binding peptide (YLFSVHWPPLKA), designated Met-pep1, reacts with Met on the cell surface and competes with HGF/scatter factor binding to Met in a dose-dependent manner. Met-pep1 is internalized by Met-expressing cells after receptor binding. Met-pep1 inhibits human leiomyosarcoma SK-LMS-1 cell proliferation in vitro. In SK-LMS-1 mouse xenografts, tumor-associated activity was imaged as early as 1 h postinjection and remained visible in some animals as late as 24 h postinjection. Conclusions: Met-pep1 specifically interacts with Met: it is internalized by Met-expressing cells and inhibits tumor cell proliferation in vitro; it is a potential diagnostic agent for tumor imaging.
Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma
Authors: Jose A. Martinez-Climent, Esperanza Vizcarra, Dolors Sanchez, David Blesa, Isabel Marugan, Isabel Benet, Françesc Sole, Francisca Rubio-Moscardo, Maria J. Terol, Joan Climent, Elena Sarsotti, Mar Tormo, Enrique Andreu, Marta Salido, Maria A. Ruiz, Felipe Prosper, Reiner Siebert, Martin J. S. Dyer, Javier Garcı́a-Conde
Journal: Blood (2001)
A CONSIDERATION OF SOME EXPERIENCES WITH ELECTRIC SHOCK TREATMENT IN MENTAL DISEASES, WITH SPECIAL REGARD TO VARIOUS PSYCHOSOMATIC PHENOMENA AND TO CERTAIN ELECTROTECHNICAL FACTORS
Authors: W. SULZBACH, K. J. TILLOTSON, V. GUILLEMIN, G. F. SUTHERLAND
Journal: American Journal of Psychiatry (1943)

1. The properties of electrical currents, which basically determine the stimulatory efficiency are: type of current, amperage and length of time stimulus is applied. The threshold cannot be computed accurately in terms of voltage, due to variations in impedance. 2. An instrument for electric shock therapy which utilizes these principles has been briefly described. 3. The experiences during use of this instrument for convulsive therapy in 55 patients have been discussed in regard to physio-pathological, and psycho-somatic observations.
Automatic Implantable Cardioverter-defibrillators
Authors: William M. Smith, Raymond E. Ideker
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Ventricular fibrillation, a loss of synchronus electrical activity in the heart which leads to hemodynamic collapse, is a leading cause of death. Because of the devastating personal and societal effects of this phenomenon, the automatic cardioverter-defibrillator has been developed for automatic detection and termination of the arrhythmia and is in widespread clinical use. Advances in circuits, leads, waveforms, and signal processing along with increased knowledge of the mechanisms of fibrillation have led to continuing improvements in this device, extending its use to many patients. A device has also been developed for the automatic or semiautomatic treatment of atrial fibrillation, an arrhythmia less life-threatening than ventricular fibrillation, but still a serious health problem. Continued improvement of these devices and the development of qualitatively new approaches hold great promise for exciting therapeutic advances in this area.
Inhibition of Neutrophil Extracellular Trap Formation after Stem Cell Transplant by Prostaglandin E<sub>2</sub>
Authors: Racquel Domingo-Gonzalez, Giovanny J. Martínez-Colón, Alana J. Smith, Carolyne K. Smith, Megan N. Ballinger, Meng Xia, Susan Murray, Mariana J. Kaplan, Gregory A. Yanik, Bethany B. Moore
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Autologous and allogeneic hematopoietic stem cell transplant (HSCT) patients are susceptible to pulmonary infections, including bacterial pathogens, even after hematopoietic reconstitution. We previously reported that murine bone marrow transplant (BMT) neutrophils overexpress cyclooxygenase-2, overproduce prostaglandin E2 (PGE2), and exhibit defective intracellular bacterial killing. Neutrophil extracellular traps (NETs) are DNA structures that capture and kill extracellular bacteria and other pathogens.Objectives: To determine whether NETosis was defective after transplant and if so, whether this was regulated by PGE2 signaling.Methods: Neutrophils isolated from mice and humans (both control and HSCT subjects) were analyzed for NETosis in response to various stimuli in the presence or absence of PGE2 signaling modifiers.Measurements and Main Results: NETs were visualized by immunofluorescence or quantified by Sytox Green fluorescence. Treatment of BMT or HSCT neutrophils with phorbol 12-myristate 13-acetate or rapamycin resulted in reduced NET formation relative to control cells. NET formation after BMT was rescued both in vitro and in vivo with cyclooxygenase inhibitors. Additionally, the EP2 receptor antagonist (PF-04418948) or the EP4 antagonist (AE3–208) restored NET formation in neutrophils isolated from BMT mice or HSCT patients. Exogenous PGE2 treatment limited NETosis of neutrophils collected from normal human volunteers and naive mice in an exchange protein activated by cAMP- and protein kinase A–dependent manner.Conclusions: Our results suggest blockade of the PGE2–EP2 or EP4 signaling pathway restores NETosis after transplantation. Furthermore, these data provide the first description of a physiologic inhibitor of NETosis.
Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP)
Authors: Nancy R Cook, Jeffrey A Cutler, Eva Obarzanek, Julie E Buring, Kathryn M Rexrode, Shiriki K Kumanyika, Lawrence J Appel, Paul K Whelton
Journal: BMJ (2007)

<b>Objective</b> To examine the effects of reduction in dietary sodium intake on cardiovascular events using data from two completed randomised trials, TOHP I and TOHP II. <b>Design </b>Long term follow-up assessed 10-15 years after the original trial. <b>Setting </b>10 clinic sites in 1987-90 (TOHP I) and nine sites in 1990-5 (TOHP II). Central follow-up conducted by post and phone. <b>Participants</b> Adults aged 30-54 years with prehypertension. <b>Intervention</b> Dietary sodium reduction, including comprehensive education and counselling on reducing intake, for 18 months (TOHP I) or 36-48 months (TOHP II). <b>Main outcome measure</b> Cardiovascular disease (myocardial infarction, stroke, coronary revascularisation, or cardiovascular death). <b>Results</b> 744 participants in TOHP I and 2382 in TOHP II were randomised to a sodium reduction intervention or control. Net sodium reductions in the intervention groups were 44 mmol/24 h and 33 mmol/24 h, respectively. Vital status was obtained for all participants and follow-up information on morbidity was obtained from 2415 (77%), with 200 reporting a cardiovascular event. Risk of a cardiovascular event was 25% lower among those in the intervention group (relative risk 0.75, 95% confidence interval 0.57 to 0.99, P=0.04), adjusted for trial, clinic, age, race, and sex, and 30% lower after further adjustment for baseline sodium excretion and weight (0.70, 0.53 to 0.94), with similar results in each trial. In secondary analyses, 67 participants died (0.80, 0.51 to 1.26, P=0.34). <b>Conclusion</b> Sodium reduction, previously shown to lower blood pressure, may also reduce long term risk of cardiovascular events.
Facilitation of the L-type calcium current in rabbit sino-atrial cells: effect on cardiac automaticity
Authors: Matteo E. Mangoni, Pierre Fontanaud, Penelope J. Noble, Denis Noble, Henri Benkemoun, Joel Nargeot, Sylvain Richard
Journal: Cardiovascular Research (2000)

Objective: The L-type Ca2+ current (ICa,L) contributes to the generation and modulation of the pacemaker action potential (AP). We investigated facilitation of ICa,L in sino-atrial cells. Methods: Facilitation was studied in regularly-beating cells isolated enzymatically from young albino rabbits (0.8–1 kg). We used the whole-cell patch-clamp technique to vary the frequency of the test depolarizations evoked at −10 mV or the conditioning diastolic membrane potential prior to the test pulse. Results: High frequencies (range 0.2–3.5 Hz) slowed the decay kinetics of ICa,L evoked from a holding potential (HP) of −80 mV in 68% of cells resulting in a larger Ca2+ influx during the test pulse. The amount of facilitation increased progressively between 0.2 and 3.0 Hz. When the frequency was changed from 0.1 to 1 Hz, the averaged increase in the time integral of ICa,L was 27±7% (n = 22). Application of conditioning voltages between −80 and −50 mV induced similar facilitation of ICa,L in 73% of cells. The maximal increase of Ca2+ entry occurred between −60 and −50 mV, and was on average 38±14% for conditioning prepulses of 5 s in duration (n = 15). Numerical simulations of the pacemaker activity showed that facilitation of ICa,L promotes stability of sino-atrial rate by enhancing Ca2+ entry, thus establishing a negative feedback control against excessive heart rate slowing. Conclusion: Facilitation of ICa,L is present in rabbit sino-atrial cells. The underlying mechanism reflects modulation of ICa,L decay kinetics by diastolic membrane potential and frequency of depolarization. This phenomenon may provide an important regulatory mechanism of sino-atrial automaticity.
Review of Adherence-Related Issues in Adolescents and Young Adults With Cancer
Authors: Phyllis Butow, Susan Palmer, Ahna Pai, Belinda Goodenough, Tim Luckett, Madeleine King
Journal: Journal of Clinical Oncology (2010)

Purpose This review aims to provide a broad overview of the issues and clinical challenges of nonadherence in adolescents and young adults (AYAs) with cancer. Nonadherence can reduce treatment efficacy, which places the patient at higher risk of relapse, adverse effects, and poor outcomes. Design A review of the English-speaking literature between 1980 and 2008 was conducted to identify relevant publications, which were supplemented by reference and author searches. Results Definition and measurement of adherence varies. Most studies have not clearly delineated an AYA age group (ie, 15-25 years) and have been dominated by leukemia and lymphoma samples. Estimates for nonadherence in this population range from 27% to 60%, with openness of family relationships and support found to predict adherence. Strategies to avoid, assess, and manage nonadherence are presented. Conclusion Overall, the evidence base for adherence and strategies to promote it in AYAs with cancer is woefully lacking. There is a need for high-quality studies that target clinically important questions, randomized controlled trials of theoretically based interventions, and development and evaluation of training programs for oncology staff in the special issues faced by AYAs with cancer.
Differential cyclophosphamide sensitivity of precursor cells in allogeneic and H-2 restricted cytotoxic responses.
Authors: M Hurme
Journal: The Journal of Experimental Medicine (1979)

Spleen cells from cyclophosphamide-treated mice responded in vitro to allogeneic stimulator cells but not to TNP-coupled syngeneic spleen cells. Similarly, cells from female mice, primed in vivo with syngeneic male cells, could not respond in vitro to male spleen cell stimulation if the mice were pretreated with cyclophosphamide. These results suggest that the precursor cells for H-2-restricted cytotoxic responses belong to a different T-cell subpopulation than the precursor cells for allogeneic responses.
Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing
Authors: Simon R Harris, Ian N Clarke, Helena M B Seth-Smith, Anthony W Solomon, Lesley T Cutcliffe, Peter Marsh, Rachel J Skilton, Martin J Holland, David Mabey, Rosanna W Peeling, David A Lewis, Brian G Spratt, Magnus Unemo, Kenneth Persson, Carina Bjartling, Robert Brunham, Henry J C de Vries, Servaas A Morré, Arjen Speksnijder, Cécile M Bébéar, Maïté Clerc, Bertille de Barbeyrac, Julian Parkhill, Nicholas R Thomson
Journal: Nature Genetics (2012)
Novel Mechanism of Apoptosis Resistance in Cancer Mediated by Extracellular PAR-4
Authors: Ravshan Burikhanov, Tripti Shrestha-Bhattarai, Shirley Qiu, Nidhi Shukla, Nikhil Hebbar, Subodh M. Lele, Craig Horbinski, Vivek M. Rangnekar
Journal: Cancer Research (2012)

Abstract Tumor suppressor PAR-4 acts in part by modulating sensitivity to apoptosis, but the basis for its activity is not fully understood. In this study, we describe a novel mechanism of antiapoptosis by NF-κB, revealing that it can block PAR-4–mediated apoptosis by downregulating trafficking of the PAR-4 receptor GRP78 from the endoplasmic reticulum to the cell surface. Mechanistic investigations revealed that NF-κB mediated this antiapoptotic mechanism by upregulating expression of UACA, a proinflammatory protein in certain disease settings. In clinical specimens of cancer, a strong correlation existed between NF-κB activity and UACA expression, relative to normal tissues. UACA bound to intracellular PAR-4 in diverse cancer cells, where it prevented translocation of GRP78 from the endoplasmic reticulum to the cell surface. This pathway of antiapoptosis could be inhibited by suppressing levels of NF-κB or UACA expression, which enhanced endoplasmic reticulum stress and restored GRP78 trafficking to the cell surface, thereby sensitizing cancer cells to apoptosis by extracellular PAR-4 or GRP78 agonistic antibody. In summary, our results identify a novel intracellular pathway of apoptosis mediated by NF-κB through UACA elevation, which by attenuating endoplasmic reticulum stress and GRP78 translocation to the cell surface can blunt the sensitivity of cancer cells to apoptosis. Cancer Res; 73(2); 1011–9. ©2012 AACR.
Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study
Authors: Kenneth J O'Byrne, Ulrich Gatzemeier, Igor Bondarenko, Carlos Barrios, Corinna Eschbach, Uwe M Martens, Yevhen Hotko, Cornelius Kortsik, Luis Paz-Ares, Jose R Pereira, Joachim von Pawel, Rodryg Ramlau, Jae-Kyung Roh, Chih-Teng Yu, Christopher Stroh, Ilhan Celik, Armin Schueler, Robert Pirker
Journal: The Lancet Oncology (2011)
Diagnosing occupational asthma: how, how much, how far?: Table 1
Authors: G. Moscato, J-L. Malo, D. Bernstein
Journal: European Respiratory Journal (2003)

Diagnosing occupational asthma is still a challenge because it is based on a stepwise approach in which the depth of investigative means may vary depending on resources. The authors herewith review the existing investigative means from the approach of outlining controversies and queries. There is no validated clinical questionnaire for diagnosing occupational asthma. Immunological investigation is limited by the lack of standardised extracts for skin-prick testing and specific immunoglobulin E assessments. Criteria for interpretation of changes in peak expiratory flow rates and bronchial responsiveness to pharmacological agents are still open to discussion. It is worth improving the methodology of specific inhalation challenges, either in the laboratory or in the workplace, to facilitate more extensive use of these tests. Validation of new means that assess airway inflammation, such as exhaled nitric oxide and induced sputum, needs to be performed. There is a need to increase the use of these diagnostic tests because the diagnosis is still too often based on “clinical impression”.
Autophagic Survival in Resistance to Histone Deacetylase Inhibitors: Novel Strategies to Treat Malignant Peripheral Nerve Sheath Tumors
Authors: Gonzalo Lopez, Keila Torres, Juehui Liu, Belinda Hernandez, Eric Young, Roman Belousov, Svetlana Bolshakov, Alexander J. Lazar, John M. Slopis, Ian E. McCutcheon, David McConkey, Dina Lev
Journal: Cancer Research (2010)

Histone deacetylase inhibitors (HDACi) show promise as cancer therapeutics; however, the full scope of their utility remains unknown. Here we report findings that strongly rationalize clinical evaluation of HDACis in malignant peripheral nerve sheath tumors (MPNST), a class of highly aggressive, therapeutically resistant, and commonly fatal malignancies that occur sporadically or in patients with the inherited neurofibromatosis type-1 (NF1) syndrome. We evaluated the effects of the chemical HDACis PCI-24781, suberoylanilide hydroxamic acid, and MS-275 on a panel of human NF1-associated and sporadic MPNSTs in vitro and in vivo. A subset of MPNSTs was found to be highly sensitive to HDACis, especially to PCI-24781. All cell lines in this group were NF1-associated. Significant proapoptotic effects were noted in vitro and in vivo and were independent of p53 mutational status. In contrast, as a group the sporadic-MPNST cells were markedly resistant to HDACi treatment. HDACis were found to induce productive autophagy in MPNST cells. Genetic and/or pharmacologic autophagy blockade resulted in significant HDACi-induced apoptosis in cells defined as resistant or sensitive, leading to abrogated growth of primary tumors and lung metastases in tumor xenograft assays. Among autophagy-associated genes expressed in response to HDACi, the immunity-related GTPase family, M was validated as a critical target in mediating HDACi-induced autophagy and enhanced apoptosis. Taken together, our findings strongly support the evaluation of HDACi currently in clinical trials as an important new therapeutic strategy to treat MPNST, including in combination with autophagy blocking combination regimens in particular for patients with sporadic MPNST.