tbuckley/cabot-search huggingface dataset:
Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes?
Authors: Delèvaux I, André M, Colombier M, Albuisson E, Meylheuc F, Bègue Rj, Piette Jc, Aumaître O
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To study the levels of procalcitonin (PCT) in various inflammatory states seen in an internal medicine department and to evaluate the possible discriminative role of PCT in differentiating bacterial infection from other inflammatory processes. <b>Methods:</b> PCT, C reactive protein (CRP), and white blood cell count (WBC) were measured in patients admitted to the department for fever or biological inflammatory syndrome, or both. The serum of 173 consecutive patients was analysed according to the aetiological diagnosis. The patients were divided into two groups: group I (n=60) with documented bacterial or fungal infection; group II (n=113) with abacterial inflammatory disease. <b>Results:</b> PCT levels were &gt;0.5 ng/ml in 39/60 (65%) patients in group I. In group II, three patients with a viral infection had slightly increased PCT levels (0.7, 0.8, and 1.1 ng/ml) as did two others, one with crystal arthritis and the other with vasculitis (0.7 ng/ml in both cases). All other patients in group II had PCT levels &lt;0.5 ng/ml. In this study a value of PCT &gt;0.5 ng/ml was taken as the marker of bacterial infection (sensitivity 65%, specificity 96%). PCT values were more discriminative than WBC and CRP in distinguishing a bacterial infection from another inflammatory process. <b>Conclusion:</b> PCT levels only rose significantly during bacterial infections. In this study PCT levels &gt;1.2 ng/ml were always evidence of bacterial infection and the cue for starting antibiotic treatment.
Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes
Authors: Roberto Piva, Elisa Pellegrino, Michela Mattioli, Luca Agnelli, Luigia Lombardi, Francesco Boccalatte, Giulia Costa, Bruce A. Ruggeri, Mangeng Cheng, Roberto Chiarle, Giorgio Palestro, Antonino Neri, Giorgio Inghirami
Journal: Journal of Clinical Investigation (2006)

Anaplastic large cell lymphomas (ALCLs) represent a subset of lymphomas in which the anaplastic lymphoma kinase (ALK) gene is frequently fused to the nucleophosmin (NPM) gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo and that ALK activity is strictly required for the survival of ALK-positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK-positive ALCL cell lines, abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell-permeable ALK inhibitors. Transcripts derived from the gene expression profiling (GEP) analysis uncovered a reproducible signature, which included a novel group of ALK-regulated genes. Functional RNAi screening on a set of these ALK transcriptional targets revealed that the transcription factor C/EBPbeta and the antiapoptotic protein BCL2A1 are absolutely necessary to induce cell transformation and/or to sustain the growth and survival of ALK-positive ALCL cells. Thus, we proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions.
Role of CFTR in Autosomal Recessive Polycystic Kidney Disease
Authors: KOICHI NAKANISHI, WILLIAM E. SWEENEY, KATHERINE MACRAE DELL, CALVIN U. COTTON, ELLIS D. AVNER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. An extensive body of in vitro data implicates epithelial chloride secretion, mediated through cystic fibrosis transmembrane conductance regulator (CFTR) protein, in generating or maintaining fluid filled cysts in MDCK cells and in human autosomal dominant polycystic kidney disease (ADPKD). In contrast, few studies have addressed the pathophysiology of fluid secretion in cyst formation and enlargement in autosomal recessive polycystic kidney disease (ARPKD). Murine models of targeted disruptions or deletions of specific genes have created opportunities to examine the role of individual gene products in normal development and/or disease pathophysiology. The creation of a murine model of CF, which lacks functional CFTR protein, provides the opportunity to determine whether CFTR activity is required for renal cyst formation in vivo . Therefore, this study sought to determine whether renal cyst formation could be prevented by genetic complementation of the BPK murine model of ARPKD with the CFTR knockout mouse. The results of this study reveal that in animals that are homozygous for the cystic gene ( bpk ), the lack of functional CFTR protein on the apical surface of cystic epithelium does not provide protection against cyst growth and subsequent decline in renal function. Double mutant mice ( bpk -/-; cftr -/-) developed massively enlarged kidneys and died, on average, 7 d earlier than cystic, non-CF mice ( bpk -/-; cftr +/±). This suggests fundamental differences in the mechanisms of transtubular fluid secretion in animal models of ARPKD compared with ADPKD.
Interleukin-2, interleukin-2 receptor and γ-interferon synthesis by peripheral blood mononuclear cells in chronic hepatitis delta virus infection
Authors: Silvio Magrin, Antonio Craxì, Claudio Carini, Paolo Colombo, Francesco Di Blasi, Giovanni Spinelli, Candida Fratazzi, Maria Concetta Messina, Guido Antonelli, Clara Ausiello, Ferdinando Dianzani, Luigi Pagliaro
Journal: Journal of Hepatology (1989)
AP4 is a mediator of epithelial–mesenchymal transition and metastasis in colorectal cancer
Authors: Rene Jackstadt, Simone Röh, Jens Neumann, Peter Jung, Reinhard Hoffmann, David Horst, Christian Berens, Georg W. Bornkamm, Thomas Kirchner, Antje Menssen, Heiko Hermeking
Journal: The Journal of Experimental Medicine (2013)

The basic helix-loop-helix transcription factor AP4/TFAP4/AP-4 is encoded by a c-MYC target gene and displays up-regulation concomitantly with c-MYC in colorectal cancer (CRC) and numerous other tumor types. Here a genome-wide characterization of AP4 DNA binding and mRNA expression was performed using a combination of microarray, genome-wide chromatin immunoprecipitation, next-generation sequencing, and bioinformatic analyses. Thereby, hundreds of induced and repressed AP4 target genes were identified. Besides many genes involved in the control of proliferation, the AP4 target genes included markers of stemness (LGR5 and CD44) and epithelial–mesenchymal transition (EMT) such as SNAIL, E-cadherin/CDH1, OCLN, VIM, FN1, and the Claudins 1, 4, and 7. Accordingly, activation of AP4 induced EMT and enhanced migration and invasion of CRC cells. Conversely, down-regulation of AP4 resulted in mesenchymal–epithelial transition and inhibited migration and invasion. In addition, AP4 induction was required for EMT, migration, and invasion caused by ectopic expression of c-MYC. Inhibition of AP4 in CRC cells resulted in decreased lung metastasis in mice. Elevated AP4 expression in primary CRC significantly correlated with liver metastasis and poor patient survival. These findings imply AP4 as a new regulator of EMT that contributes to metastatic processes in CRC and presumably other carcinomas.
Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation
Authors: E. D. Wildschut, M. N. Hanekamp, N. J. Vet, R. J. Houmes, M. J. Ahsman, R. A. A. Mathot, S. N. de Wildt, D. Tibboel
Journal: Intensive Care Medicine (2010)

In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO.Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms.Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred.This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes.
The tumour suppressor Ras-association domain family protein 1A (RASSF1A) regulates TNF-α signalling in cardiomyocytes
Authors: Tamer M.A. Mohamed, Min Zi, Sukhpal Prehar, Arfa Maqsood, Riham Abou-Leisa, Loan Nguyen, Gerd P. Pfeifer, Elizabeth J. Cartwright, Ludwig Neyses, Delvac Oceandy
Journal: Cardiovascular Research (2014)

Tumour necrosis factor-α (TNF-α) plays a key role in the regulation of cardiac contractility. Although cardiomyocytes are known to express the TNF-α receptors (TNFRs), the mechanism of TNF-α signal transmission is incompletely understood. The aim of this study was to investigate whether the tumour suppressor Ras-association domain family protein 1 isoform A (RASSF1A) modulates TNF-α signalling in cardiomyocytes.We used RASSF1A knockout (RASSF1A(-/-)) mice and wild-type (WT) littermates in this study. Acute stimulation with a low dose of TNF-α (10 µg/kg iv) increased cardiac contractility and intracellular calcium transients' amplitude in WT mice. In contrast, RASSF1A(-/-) mice showed a blunted contractile response. Mechanistically, RASSF1A was essential in the formation of the TNFR complex (TNFRC), where it functions as an adaptor molecule to facilitate the recruitment of TNFR type 1-associated death domain protein and TNFR-associated factor 2 to form the TNF-α receptor complex. In the absence of RASSF1A, signal transmission from the TNF-α receptor complex to the downstream effectors, such as cytoplasmic phospholipase A2 and protein kinase A, was attenuated leading to the reduction in the activation of calcium handling molecules, such as L-type Ca(2+) channel and ryanodine receptors.Our data indicate an essential role of RASSF1A in regulating TNF-α signalling in cardiomyocytes, with RASSF1A being key in the formation of the TNFRC and in signal transmission to the downstream targets.
Guidelines for Infection Control in Intravenous Therapy
Authors: Donald A. Goldmann, Dennis G. Maki, Frank S. Rhame, Allen B. Kaiser, James H. Tenney, John V. Bennett
Journal: Annals of Internal Medicine (1973)

Infusion-associated septicemia is an appreciable hazard to the more than 8 million patients who receive intravenous therapy in U.S. hospitals each year. Rigorous infection control measures are necessary if the risk of sepsis is to be reduced. Based on CDC studies and a critical review of previously published investigations, guidelines are proposed for the prevention and management of infections caused by intravenous therapy.
Behavioural and social correlates of sedentary time in young people
Authors: E M F van Sluijs, A Page, Y Ommundsen, S J Griffin
Journal: British Journal of Sports Medicine (2008)

Objective In this study, behavioural and social correlates of objectively measured sedentary time in young people were identified. Design Cross-sectional analysis of data from the European Youth Heart Study (EYHS). Setting Schools in Denmark, Estonia, Portugal and Norway. Participants Respondents were invited using a twostage cluster sampling procedure. Analyses include 2107 children (9–10 years old) and adolescents (14–15 years old). Assessment of independent variables Seven behavioural and 15 social variables assessed by parental and computerised child questionnaires. Main outcome measure Sedentary activity as assessed by accelerometry (10 min blocks at &lt;200 counts/min). Analyses were stratified by country, and interactions with grade and sex were investigated. Results Adolescents were more sedentary than children (335.4 (90.4 min/day) vs 217.2 (75.6 min/day), p&lt;0.001). Patterns of associations differed across countries. High computer use and no television viewing before school in Norway, and being sedentary during school breaks in Estonia were positively associated with sedentary time. No behavioural variables were associated with sedentary time in the Danish and Portuguese models. Socioeconomic position was positively associated with sedentary time in Portugal and Estonia, father's body mass index negatively in the Estonian model. Norwegian participants with a game console at home and Portuguese participants with a television in their bedroom were more sedentary. Conclusions A single strategy aimed at reducing sedentary behaviour is unlikely to be effective across Europe as the target populations and behaviours of focus differ between countries. Targeting high socioeconomic groups in Portugal and Estonia or focusing on reducing computer use in Norway might be effective intervention strategies to reduce overall sedentary time.
Novel <i>Cytosine Deaminase</i> Fusion Gene Enhances the Effect of Radiation on Breast Cancer in Bone by Reducing Tumor Burden, Osteolysis, and Skeletal Fracture
Authors: Michael Goblirsch, Pawel Zwolak, Margaret L. Ramnaraine, Weihong Pan, Christine Lynch, Parham Alaei, Denis R. Clohisy
Journal: Clinical Cancer Research (2006)

Abstract Background: Painful breast carcinoma metastases in bone are a common manifestation of malignant disease. Eradication of these tumors can be evasive, and as a result, skeletal morbidity increases with disease progression. Experimental Design: The treatment potential of cytosine deaminase (CD) gene therapy combined with radiation treatment was evaluated in vitro and in vivo using a 4T1 murine breast carcinoma model. 4T1 carcinoma cells were transduced with a fusion gene encoding the extracellular and transmembrane domains of the human nerve growth factor receptor and the cytoplasmic portion of the yeast CD gene (NGFR-CDy). Results and Conclusions: CD-expressing tumor cells (4TCDy) were highly sensitive to treatment by 5-fluorocytosine prodrug (P &amp;lt; 0.0001). 5-Fluorocytosine treatment of 4TCDy, but not 4T1 cells, enhanced the effects of radiation in vitro (P &amp;lt; 0.0001). 5-Fluorocytosine prodrug treatment also increased the therapeutic potential of radiation in vivo. Mice with 4TCDy intrafemoral tumors showed increased effectiveness of radiation based on improved reductions in tumor size, reductions in tumorigenic osteolysis, and a decrease in skeletal fractures (P &amp;lt; 0.01).
Measurements of Exhaled Nitric Oxide with the Single-Breath Technique and Positive Expiratory Pressure in Infants
Authors: JOHANNES H. WILDHABER, GRAHAM L. HALL, STEPHEN M. STICK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The aim of this study was to adapt the single-breath technique with positive expiratory pressure to measure exhaled nitric oxide (eNO) in infants. We hypothesized that exhaled eNO was greater in wheezy than in healthy infants. We studied 30 infants (16 wheezy and 14 healthy). The forced expiratory volume in 0.5 s (FEV0.5) was determined with the raised volume rapid thoracic compression technique, and eNO was measured during constant expiratory flow with a rapid-response chemiluminescence analyzer. After passive inflation to a preset pressure of 20 cm H2O, thoracic compression with an inflatable jacket caused forced expiration to occur through a face-mask with an expiratory flow resistor attached. During the forced expiration, the jacket pressure was increased to maintain a constant driving mouth pressure and hence a constant expiratory flow (50 ml/s). The mean level of eNO in the wheezy infants (31.8 ppb) was significantly higher than the level in healthy infants (18.8 ppb) (p = 0.03). A family history of atopy in parents was associated with increased eNO levels (p < 0.001) independent of age, sex, weight, length, wheezing, and FEV0.5. We conclude that the single-breath technique with positive expiratory pressure is a feasible method for measuring eNO in infants. Levels of eNO were significantly higher in wheezy infants and in those with a family history of atopy.
Erythropoietin and Erythropoietin Receptor Coexpression Is Associated with Poor Survival in Stage I Non–Small Cell Lung Cancer
Authors: Pierre Saintigny, Benjamin Besse, Patrice Callard, Anne-Claire Vergnaud, Sébastien Czernichow, Magali Colombat, Philippe Girard, Pierre Validire, Jean-Luc Breau, Jean-François Bernaudin, Jean-Charles Soria
Journal: Clinical Cancer Research (2007)

This study was designed to evaluate the prognostic effect of erythropoietin (EPO) and EPO receptor (EPO-R) expression in stage I non-small cell lung cancer (NSCLC) patients.EPO and EPO-R expression in 158 tumor samples from resected stage I NSCLC was evaluated using immunohistochemistry and tissue array technology.EPO-R and EPO were highly expressed in 20.9% and 35.4% of tumors, respectively. High EPO-R expression compared with negative or low-level expression was associated with a poor 5-year disease-specific survival (60.6% versus 80.8%; P = 0.01, log-rank test). High EPO expression compared with negative and low-level expression was associated with a trend toward a poor 5-year disease-specific survival (69.6% versus 80.4%; P = 0.13, log-rank test). A high level of EPO-R and EPO coexpression was associated with a poor 5-year disease-specific survival compared with other groups of patients (50.0% versus 80.0% survival at the end of follow-up; P = 0.005, log-rank test). In multivariate analysis for disease-specific survival, high-level EPO-R and EPO coexpression was an independent prognostic factor for disease-specific survival (hazard ratio, 2.214; 95% confidence interval, 1.012-4.848; P = 0.046).These results establish the pejorative prognostic value of EPO and EPO-R expression in early-stage resected NSCLC and suggest a potential paracrine and/or autocrine role of endogenous EPO in NSCLC aggressiveness.
Autologous graft-versus-host disease–like syndrome after an alemtuzumab-containing conditioning regimen and autologous stem cell transplantation for chronic lymphocytic leukemia
Authors: Thorsten Zenz, Matthias Ritgen, Peter Dreger, Alexander Kröber, Thomas F. Barth, Richard Schlenk, Sebastian Böttcher, Michael J. Hallek, Michael Kneba, Donald Bunjes, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2006)
Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery
Authors: Y Huang
Journal: Cardiovascular Research (2003)

Urocortin possesses cardioprotective properties against the damaging effects of ischemia/reperfusion injury. Our previous study demonstrated that urocortin can induce both endothelium-dependent and -independent coronary relaxation. However, the mechanisms thereby urocortin triggers endothelium-independent relaxation have not been investigated. The present study aimed to examine the role of cyclic AMP and Ca(2+)-activated K(+) channels in the relaxant response to urocortin in the isolated endothelium-denuded rat left anterior descending coronary arteries.Changes in vessel tension were measured by using a force transducer built in a Multi Myograph System.In 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619)-contracted rings, urocortin-induced relaxation (pD(2): 8.40+/-0.04) was significantly reduced by cyclic AMP-dependent protein kinase (PKA) inhibitors, Rp-cAMPS triethylamine (Rp-cAMPS) and KT 5720. Treatment with the large-conductance Ca(2+)-activated K(+) channel blockers, iberiotoxin or tetraethylammonium ions (TEA(+)) attenuated urocortin-induced relaxation; this effect was abolished in the presence of 200 nmol/l KT 5720. In contrast, apamin (small-conductance Ca(2+)-activated K(+) channel blocker), glibenclamide (ATP-sensitive K(+) channel blocker), or BaCl(2) (inwardly rectifier K(+) channel blocker) had no effect. Urocortin-induced relaxation was reduced in rings contracted with increasing concentrations of extracellular K(+) (35 and 50 mmol/l). Treatment with TEA(+) or Rp-cAMPS inhibited the relaxant effect of urocortin in 35 mmol/l K(+)-contracted rings. Combined treatment with TEA(+) and Rp-cAMPS had no additional effect. Similarly, forskolin produced significantly less relaxant response in 50 mmol/l K(+)-contracted than U46619-contracted rings. Forskolin-induced relaxation was attenuated by pretreatment with 3 mmol/l TEA(+).Urocortin relaxed the rat coronary artery in substantial part via activation of the vascular Ca(2+)-activated K(+) channels and this effect appears to be primarily mediated through PKA-dependent intracellular mechanisms.
Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer
Authors: M.T.W. Teo, L. Dyrskjøt, J. Nsengimana, C. Buchwald, H. Snowden, J. Morgan, J.B. Jensen, M.A. Knowles, G. Taylor, J.H. Barrett, M. Borre, T.F. Ørntoft, D.T. Bishop, A.E. Kiltie
Journal: Annals of Oncology (2014)

Muscle-invasive bladder cancer (MIBC) can be cured by radical radiotherapy (RT). We previously found tumour MRE11 expression to be predictive of survival following RT in MIBC, and this was independently validated in a separate institute. Here, we investigated germline MRE11A variants as possible predictors of RT outcomes in MIBC, using next-generation sequencing (NGS).
THE RELATION OF DOSE OF BACTERIA TO GROUP INFECTION
Authors: Arthur L. Bloomfield, Augustus R. Felty
Journal: The Journal of Experimental Medicine (1924)

A study has been made of the peritoneal reaction in mice after injection of different bacteria in graded dose. Organisms were employed to which the animals were fairly resistant. Under these conditions it was found that as the dosage was decreased a more or less critical point was reached below which infection failed to be initiated. The possible clinical bearings of this observation are discussed.
HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen
Authors: Jerald P. Radich, Ted Gooley, William Bensinger, Thomas Chauncey, Reginald Clift, Mary Flowers, Paul Martin, John Slattery, Debbie Sultan, Frederick R. Appelbaum
Journal: Blood (2003)