tbuckley/cabot-search huggingface dataset:
Impact of Wait Times on Survival for Women With Uterine Cancer
Authors: Lorraine M. Elit, Erin M. O'Leary, Gregory R. Pond, Hsien-Yeang Seow
Journal: Journal of Clinical Oncology (2013)

Purpose To determine whether wait time from histologic diagnosis of uterine cancer to time of definitive surgery by hysterectomy had an impact on all-cause survival. Patients and Methods Women in Ontario with a confirmed histopathologic diagnosis of uterine cancer between April 1, 2000, and March 31, 2009, followed by surgery were identified in the Ontario Cancer Registry. Survival was calculated by using the Kaplan-Meier method. Factors were evaluated for their prognostic effect on survival by using Cox proportional hazards regression. Wait time was evaluated in a multivariable model after adjusting for other significant factors. Results The final study population included 9,417 women; 51.9% had surgery by a gynecologist, and 69.9% had endometrioid adenocarcinoma. Five-year survival for women with wait times of 0.1 to 2, 2.1 to 6, 6.1 to 12, or more than 12 weeks was 71.1%, 81.8%, 79.5%, and 71.9%, respectively. Wait times of ≤ 2 weeks were adversely prognostic for survival after adjusting for other significant factors in the multivariable model, and patients with wait times of more than 12 weeks had worse survival than those who had wait times between 2.1 and 12.0 weeks. Conclusion To the best of our knowledge, this is the first report in a large population-based cohort demonstrating that longer wait times from diagnosis of uterine cancer to definitive surgery have a negative impact on overall survival.
Crucial Role of the CCL2/CCR2 Axis in Neointimal Hyperplasia After Arterial Injury in Hyperlipidemic Mice Involves Early Monocyte Recruitment and CCL2 Presentation on Platelets
Authors: Andreas Schober, Alma Zernecke, Elisa A. Liehn, Philipp von Hundelshausen, Sandra Knarren, William A. Kuziel, Christian Weber
Journal: Circulation Research (2004)

Monocyte chemoattractant protein-1 (also known as CC chemokine ligand 2 [CCL2]) and its receptor CC chemokine receptor 2 (CCR2) play a central role in the inflammatory response and neointimal formation after vascular injury. In the context of hyperlipidemia, this appears to involve neointimal monocyte infiltration. Hence, we investigated the function of the CCL2/CCR2 axis in early monocyte recruitment to injured arteries. Wire-induced injury of the carotid artery in apoE-/- mice caused a rapid increase of JE/CCL2 protein in the vessel wall peaking at 24 hours after injury, whereas serum JE/CCL2 was increased solely at 6 hours and blood cell-associated levels were unaltered, as demonstrated by enzyme-linked immunosorbent assay. Immunohistochemistry revealed intense staining for JE/CCL2 in smooth muscle cells (SMCs) and in association with platelets adherent to the denuded vessel wall 24 hours after injury. In vitro, exogenous or SMC-derived JE/CCL2 binds to the platelet surface and triggers monocyte arrest on adherent platelets but not on SMCs in flow assays. Accordingly, monocyte arrest in ex vivo perfused apoE-/- carotid arteries isolated 24 hours after injury was profoundly inhibited by pretreatment with a JE/CCL2 antibody. In CCR2-/-/apoE-/- mice, neointimal plaque area was reduced by 47% compared with CCR2+/+/apoE-/- mice. Moreover, CCR2 deletion markedly decreased neointimal macrophage content while expanding SMC content. Vascular JE/CCL2 expressed by SMCs and immobilized by adherent platelets after endothelial denudation is crucial for mediating early monocyte recruitment to injured arteries in hyperlipidemic mice. This mechanism may explain reduced neointimal macrophage infiltration and lesion formation in CCR2-deficient apoE-/- mice.
From SARS to Ebola – 10 years of disease prevention and control at ECDC
Authors: Andrea Ammon
Journal: Eurosurveillance (2015)

Preview this article: From SARS to Ebola – 10 years of disease prevention and control at ECDC, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/20/37/eurosurv-20-30016-1-1.gif
THE INITIATION OF TREATMENT OF UNMANAGEABLE PSYCHOTICS WITH INTRAMUSCULAR ADMINISTRATION OF TRIFLUOPERAZINE COMBINED WITH CHLORPROMAZINE
Authors: JOSEPH MANN
Journal: American Journal of Psychiatry (1963)

A combined intramuscular administration of trifluoperazine with chlorpromazine was used in 36 highly psychotic male patients aged 15 to 51. Remarkable improvement was observed within from 1 to 3 days of treatment, depending on the degree of disturbance. There were only 2 patients who needed a higher or a lower dosage, respectively, the average being 2 mg. of trifluoperazine and 50 mg. of chlorpromazine. The advantages of the intramuscular combination of these drugs are 1. An almost immediate response to the medication; 2. Shortening or elimination of seclusion or restraining periods; 3. Shortening of the initial phase of hospitalization; 4. Speeding of the patient's readiness for intensive psychotherapy and oral medication; 5. Benefit to other patients who are not subjected to witnessing severely-disturbed behavior of others; 6. Lessening of anxiety and nursing problems for attending personnel in the ward.
A Novel Mechanism by which Hepatocyte Growth Factor Blocks Tubular Epithelial to Mesenchymal Transition
Authors: Junwei Yang, Chunsun Dai, Youhua Liu
Journal: Journal of the American Society of Nephrology (2004)

Hepatocyte growth factor (HGF) is a potent antifibrotic cytokine that blocks tubular epithelial to mesenchymal transition (EMT) induced by TGF-beta1. However, the underlying mechanism remains largely unknown. This study investigated the signaling events that lead to HGF blockade of the TGF-beta1-initiated EMT. Incubation of human kidney epithelial cells HKC with HGF only marginally affected the expression of TGF-beta1 and its type I and type II receptors, suggesting that disruption of TGF-beta1 signaling likely plays a critical role in mediating HGF inhibition of TGF-beta1 action. However, HGF neither affected TGF-beta1-induced Smad-2 phosphorylation and its subsequent nuclear translocation nor influenced the expression of inhibitory Smad-6 and -7 in tubular epithelial cells. HGF specifically induced the expression of Smad transcriptional co-repressor SnoN but not Ski and TG-interacting factor at both mRNA and protein levels in HKC cells. SnoN physically interacted with activated Smad-2 by forming transcriptionally inactive complex and overrode the profibrotic action of TGF-beta1. In vivo, HGF did not affect Smad-2 activation and its nuclear accumulation in tubular epithelium, but it restored SnoN protein abundance in the fibrotic kidney in obstructive nephropathy. Hence, HGF blocks EMT by antagonizing TGF-beta1's action via upregulating Smad transcriptional co-repressor SnoN expression. These findings not only identify a novel mode of interaction between the signals activated by HGF receptor tyrosine kinase and TGF-beta receptor serine/threonine kinases but also illustrate the feasibility of confining Smad activity as an effective strategy for blocking renal fibrosis.
Abstract 18009: Chronic Spinal Cord Stimulation Preserves Cardiac Sympathetic Responses and Normalizes Noradrenergic Gene Expression in Stellate Ganglion in a Canine Heart Failure Model
Authors: Jeffrey L Ardell, Cherie E Bond, Elizabeth M Southerland, Donald B Hoover, Eric Beaumont
Journal: Circulation (2013)

Background: Myocardial infarction (MI) leads to adverse remodeling of the heart and cardiac neuronal hierarchy, both contributing to the development of heart failure (HF). Our previous work demonstrated that thoracic spinal cord stimulation (SCS) improved parasympathetic efferent function and survival in a canine model of HF induced by MI and mitral regurgitation (MR). The objective of this study was to determine whether SCS also had beneficial effects on the sympathetic element of the cardiac neuronal hierarchy. Methods: A HF model was created in 15 canines by performing sequential surgeries to generate MI and then MR. SCS electrodes and generators were implanted during the first surgery. Seven of the MI/MR animals received SCS (T1-T5; 20 Hz, 200 μsec, 90% of motor threshold) starting one week after MR induction. Generators were not activated in the sham SCS group (n=8). Canines were anesthetized for terminal experiments to record cardiac responses to stellate ganglion stimulation and then to collect the stellate ganglia for RNA analysis by Q-PCR. Results: MI/MR blunted the chronotropic and inotropic responses to stimulation of the right or left stellate ganglia. Treatment with reactive SCS significantly improved functional responses to right or left stellate stimulation. For example, right stellate stimulation evoked the following percent changes in sham SCS vs SCS: Cardiac output, 20.6±3.8 vs 66.2±9.2; LV +dp/dt, 38.3±10.2 vs 112.8±13.1; and LV -dp/dt, 13.8±8.3 vs 72.6±12.1 (P&lt;0.05 for all). RNA analysis of stellate ganglia showed that the sham SCS group had significantly increased expression of tyrosine hydroxylase and vesicular monoamine transporter 2 and decreased expression of α2 adrenergic receptor mRNA compared to the SCS treatment group and an acute control group (n=8). Conclusion: Chronic MI/MR results in impaired functional sympathetic control of cardiac function and corresponding molecular changes in the stellate ganglion reflective of excessive and adverse sympathetic activation. Therapeutic SCS ameliorates adverse changes in sympathetic function and gene expression in canines with MI/MR.
MicroRNA Dissects Out Dangerous Pancreatic Cysts from All the Rest
Authors: Ryan M. Thomas, Jason B. Fleming
Journal: Clinical Cancer Research (2012)

Malignant transformation of pancreatic cysts occurs in only a fraction of patients. The diagnostic dilemma is identifying which cysts pose a cancerous threat. Cyst fluid has been analyzed in a variety of ways to answer this question but the microRNA (miRNA) profile of the fluid may finally hold the answer.
Identification of <i>SFRP1</i> as a Candidate Mediator of Stromal-to-Epithelial Signaling in Prostate Cancer
Authors: Margaret S. Joesting, Steve Perrin, Brian Elenbaas, Stephen E. Fawell, Jeffrey S. Rubin, Omar E. Franco, Simon W. Hayward, Gerald R. Cunha, Paul C. Marker
Journal: Cancer Research (2005)

Abstract Genetic changes in epithelial cells initiate the development of prostatic adenocarcinomas. As nascent tumors grow and undergo progression, epithelial tumor cells are intimately associated with stromal cells. Stromal cells within the tumor microenvironment acquire new properties, including the capacity to promote phenotypic and genetic progression in adjacent epithelial cells. Affymetrix microarrays were used to identify 119 genes differentially expressed between normal-derived and carcinoma-derived prostatic stromal cells. These included 31 genes encoding extracellular proteins that may act as stromal-to-epithelial paracrine signals. Further investigation of one of these genes, secreted frizzled related protein 1 (SFRP1), revealed that its expression parallels prostatic growth with high expression during prostatic development, low expression in the adult prostate, and elevated expression in prostatic tumor stroma. In addition, as prostatic epithelial cells progressed to a tumorigenic state under the influence of tumor stroma, SFRP1 became overexpressed in the progressed epithelial cells. To further understand the roles of SFRP1 in the prostate, we tested the affects of increased SFRP1 levels on prostatic tissues and cells. Treatment of developing prostates with SFRP1 in culture led to increased organ growth. Treatment of a human prostatic epithelial cell line with SFRP1 led to increased proliferation, decreased apoptosis, and decreased signaling through the Wnt/β-catenin pathway in vitro and increased proliferation in vivo. These data suggest that overexpression of SFRP1 by prostatic tumor stroma may account for the previously reported capacity of prostatic tumor stroma to provide a pro-proliferative paracrine signal to adjacent epithelial cells.
Cellular Uptake Mechanisms of <sup>99m</sup> TcN-NOET in Cardiomyocytes From Newborn Rats
Authors: Laurent Riou, Catherine Ghezzi, Olivier Mouton, Jean-Paul Mathieu, Roberto Pasqualini, Michel Comet, Daniel Fagret
Journal: Circulation (1998)

Bis[N-ethoxy,N-ethyl(dithiocarbamato)]nitrido Tc (V) (TcN-NOET) is a new technetium complex proposed as a tracer of myocardial perfusion. However, its cellular uptake mechanisms are unknown, although membrane localization on rat heart preparations and preferential binding to polymorphonuclear neutrophils (PMNs) have been reported. Because of the central role of calcium in PMN actions, a relationship was hypothesized between this ion flux and TcN-NOET cellular uptake.The mechanisms of cellular uptake of TcN-NOET were investigated in newborn rat cardiomyocytes by study of the effect of calcium channel modulators on tracer binding. Nifedipine had no effect on tracer uptake at 1 minute. However, verapamil 0.1 micromol/L and diltiazem 0.5 micromol/L induced a 40% decrease in uptake. Conversely, Bay K 8644 0.25 micromol/L increased TcN-NOET uptake by 73%. Alterations in other membrane ion transports failed to modify tracer uptake, indicating the specificity of the relationship between TcN-NOET uptake and calcium channels. Kinetic studies indicated that cellular net accumulation of the tracer was slow (t1/2=28.5 minutes) and retention was prolonged (84% of initial activity retained after 120 minutes of washout). The energy dependence of TcN-NOET uptake was investigated after 60 minutes of metabolic inhibition by iodoacetic acid plus rotenone. The ATP decrease was not associated with reduction in tracer uptake at 1 minute (114.9+/-21.9% of control, P=NS).The decrease in uptake observed with verapamil and diltiazem, the increase with Bay K 8644, and the lack of effect with nifedipine suggest that TcN-NOET binds to L-type calcium channels in the open configuration, without entering cardiomyocytes. The kinetics of TcN-NOET accumulation and retention are slow, and the mechanism for cellular uptake is not energy-dependent. From a clinical point of view, the effect of concurrent treatment by calcium inhibitors on myocardial binding of TcN-NOET should be taken into account.
Large-scale Analysis of <i>PDGFRA</i> Mutations in Melanomas and Evaluation of Their Sensitivity to Tyrosine Kinase Inhibitors Imatinib and Crenolanib
Authors: Jie Dai, Yan Kong, Lu Si, Zhihong Chi, Chuanliang Cui, Xinan Sheng, Lili Mao, Siming Li, Bin Lian, Ruifeng Yang, Shujing Liu, Xiaowei Xu, Jun Guo
Journal: Clinical Cancer Research (2013)

Platelet-derived growth factor receptor α (PDGFRA) is a target for tyrosine kinase inhibitor (TKI)-based targeted therapy. Dysregulation of PDGFRA has been reported in many cancers. However, PDGFRA mutations in melanomas have not been well studied. We analyzed the genetic mutations of PDGFRA in Chinese patients with melanoma and determined the inhibitory potency of TKIs, such as imatinib and crenolanib, on mutant PDGFRA.Of note, 351 melanoma tissue samples were examined for genetic mutations in exons 12, 14, and 18 of PDGFRA. Activities of mutations in response to imatinib and crenolanib were analyzed by Western blotting of tyrosine-phosphorylated PDGFRA and cell proliferation assays.PDGFRA mutations were observed in 4.6% (16 of 351) of melanomas, and these mutations were mainly detected in acral and mucosal melanomas. PDGFRA mutations seem to be mutually exclusive with KIT mutations, but may coexist with BRAF and NRAS mutations. The genetic mutations of PDGFRA were unrelated to the age, thickness, and ulceration status of primary melanomas. Thirteen mutations were not reported before, and five (P577S, V658A, R841K, H845Y, and G853D) of them resulted in strong autophosphorylation of PDGFRA. Crenolanib showed higher potency than imatinib in inhibiting the kinase activity of PDGFRA. Except that V658A mutation was imatinib-resistant, all the other mutations were sensitive to both imatinib and crenolanib.PDGFRA mutations are detected in a small population of melanoma patients. Our study suggests that patients with melanoma harboring certain PDGFRA mutations may benefit from imatinib and crenolanib treatment.
S54 Neural Respiratory Drive Measured Using Parasternal Intercostal Muscle Electromyography In Patients With Interstitial Lung Disease
Authors: A. Kaaba, C. Jolley, v. MacBean, C. Reilly, S. Birring, J. Moxham, G. Rafferty
Journal: Thorax (2014)

<h3>Introduction</h3> Forced vital capacity (FVC) and gas transfer (TLCO) are often used to assess disease severity and monitor progression in patients with interstitial lung disease (ILD). Difficulty in performing the required manoeuvres, particularly in severe disease, and inherent measurement variability makes detection of clinically important changes difficult using these parameters. There is, therefore, a need for new biomarkers in this patient group. Neural respiratory drive (NRD) reflects the load on the respiratory system and the capacity of the respiratory muscles. Parasternal intercostal muscle electromyography (EMGpara) provides a non-invasive measure of NRD which relates to disease severity and breathlessness in obstructive lung diseases. Measurements of EMGpara in ILD could potentially quantify overall disease severity. <h3>Aim</h3> The aim of the study was to investigate the relationships between EMGpara, lung function, breathlessness, functional status and quality of life (QoL) in ILD. <h3>Method</h3> EMGpara was measured in 45 patients with a range of fibrotic lung diseases using surface electrodes placed in the second intercostal spaces bilaterally. Mean peak root mean square EMGpara per breath was calculated and expressed as a percentage of maximum EMGpara (EMGpara%max). The neural respiratory drive index (NRDI) was derived by multiplying EMGpara%max by the respiratory rate. Spirometry and lung gas transfer were performed and the composite physiologic index (CPI) calculated. Six minute walk test (6MWT) and 4 metre gait speed (4MGS) were used to determine functional status. Health-related quality of life was assessed with the King’s Brief Interstitial Lung Disease (K-BILD) and the St George’s Respiratory Questionnaires (SGRQ). The Baseline Dyspnea Index (BDI) was used to grade breathlessness. <h3>Results</h3> NRDI correlated significantly with VC%predicted (r = -0.36, p = 0.018) and the CPI (r = 0.40, p = 0.01) No significant correlations were found between EMGpara or NRDI and breathlessness, QoL or functional status. <h3>Conclusion</h3> EMGpara is a feasible measure in ILD. EMGpara correlates with prognostic markers suggesting potential value as a biomarker integrating important pathophysiological changes in lung mechanics in fibrotic ILDs. The lack of association with QoL measures and BDI requires further investigation.
Nephrin Dissociates from Actin, and Its Expression Is Reduced in Early Experimental Membranous Nephropathy
Authors: Huaiping Yuan, Emiko Takeuchi, Gregory A. Taylor, Margaret McLaughlin, Dennis Brown, David J. Salant
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. These studies examined the expression of the podocyte slit diaphragm protein nephrin and its association with actin at the onset of proteinuria in passive Heymann nephritis (PHN), a rat model of human membranous nephropathy. Four days after immunization, 58% of PHN rats had mild proteinuria. At that time, most slit diaphragms were still visible on electron microscopy; however, in those locations where the deposits encroached on the filtration slits, the slit diaphragms were either displaced or absent. On day 7, the PHN rats were severely proteinuric, and most slit diaphragms were either absent, displaced, or replaced by occluding-type junctions. Immunofluorescence microscopy with antibodies to the external and cytoplasmic domains of nephrin showed a progressive loss of staining and a change in the distribution of nephrin from an interrupted linear pattern in normal controls to a more dispersed and clustered pattern in PHN. In contrast, the intensity of staining for ZO-1 and CD2-associated protein (CD2AP), two other proteins that are located on the cytoplasmic face of the slit diaphragm, was undiminished. Immunogold electron microscopy confirmed the progressive disappearance of nephrin from podocyte foot processes and retention of CD2AP. Glomeruli and glomerular cell membranes were extracted sequentially with Triton X-100, followed by DNase I or potassium iodide to depolymerize actin. Western blot analysis of the extracts showed a progressive decline of total nephrin on days 4 and 7 of PHN as well as a reduction in the actin-associated fraction. These findings show that nephrin partly dissociates from actin at the onset of podocyte injury in PHN. This is accompanied by a progressive loss of nephrin from the podocyte foot processes and prominent changes in the morphology of the slit diaphragms. These events may underlie the loss of podocyte barrier function in membranous nephropathy.
Consciousness versus states of being conscious
Authors: Ernst Pöppel
Journal: Behavioral and Brain Sciences (1997)

States of being conscious (S) can be defined on the basis of temporal information processing. A high-frequency mechanism provides atemporal system states with periods of approximately 30 msec to implement the functional connection of distributed activities allowing the construction of primordial events; a low frequency mechanism characterized by automatic temporal integration sets up temporal windows with approximately 3 seconds duration. This integration mechanism can be used to define S. P-consciousness and A-consciousness as conceived of by Block can be mapped onto these neuronal mechanisms.
Validation of EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)
Authors: Raphaèle Seror, Elke Theander, Johan G Brun, Manel Ramos-Casals, Valeria Valim, Thomas Dörner, Hendrika Bootsma, Athanasios Tzioufas, Roser Solans-Laqué, Thomas Mandl, Jacques-Eric Gottenberg, Eric Hachulla, Kathy L Sivils, Wan-Fai Ng, Anne-Laure Fauchais, Stefano Bombardieri, Guido Valesini, Elena Bartoloni, Alain Saraux, Matija Tomsic, Takayuki Sumida, Susumu Nishiyama, Roberto Caporali, Aike A Kruize, Cristina Vollenweider, Philippe Ravaud, Claudio Vitali, Xavier Mariette, Simon J Bowman
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To validate the two recently developed disease activity indexes for assessment of primary Sjögren9s syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). <h3>Methods</h3> A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjögren9s Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores. <h3>Results</h3> Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r=0.59; ESSRPI with PGA: r=0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores. <h3>Conclusions</h3> ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.