tbuckley/cabot-search huggingface dataset:
Structural and electrical ventricular remodeling in rat acute myocarditis and subsequent heart failure
Authors: Y WAKISAKA
Journal: Cardiovascular Research (2004)

We reported that experimental autoimmune myocarditis (EAM) rats showed dramatic changes in ventricular action potential and enhanced arrhythmogenicity in the acute phase, but mechanisms for this are still unclear. To investigate the mechanisms of cardiac remodeling in acute myocarditis and subsequent heart failure, physiological and molecular changes were evaluated along the time course of EAM.Six-week-old Lewis rats were immunized with porcine cardiac myosin. On days 14, 21, 35 and 60 after immunization, histology, hemodynamics and electrophysiological parameters (i.e., effective refractory period (ERP), monophasic action potential duration (MAPD) and PVC inducibility) were evaluated and compared with control rats. After these studies, the expression levels of Kv(+) and L-Ca(2+) channels, ion transporters and BNP expressions in the left ventricle were examined by quantitative real time RT-PCR and Western blot analysis.EAM rats showed acute myocarditis with massive infiltration of the mononuclear cells on days 14 and 21. Subsequently, a chronic dilated cardiomyopathy (DCM)-like structural change was observed on day 60. Hemodynamic parameters were worse in EAM than controls. ERP and MAPD were longer in EAM than controls, with a peak on day 21, which was parallel to PVC inducibility. mRNA levels of Kv4.2, Kv1.5, KChIP2, frequenin and SERCA2a, and the protein levels of Kv4.2 and Kv1.5, were reduced, especially in the acute phase.The initial reduction of Ito-related molecules, such as the expression levels of Kv4.2, 1.5, frequenin and KChIP2, and the prolongation of MAPD are considered to be a key mechanism of ventricular remodeling and cause the characteristic clinical findings in EAM in the acute inflammatory phase and chronic DCM phase.
Anal Carcinoma, Version 2.2012
Authors: Al B. Benson, J. Pablo Arnoletti, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Raza A. Dilawari, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, James W. Fleshman, Charles S. Fuchs, Jean L. Grem, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small, Constantinos T. Sofocleous, Alan P. Venook, Christopher Willett, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2012)

The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings.
Effects of experimental Mycoplasma pulmonis infection on sensory neuropeptides and airway mucosa in the rat
Authors: T Norlander, L Nilsson, C Rivero, T Midvedt, M Lidegran, B Carlsoo, P Stierna
Journal: European Respiratory Journal (1997)

The effect of airway infection on neurogenic inflammation is not known. The present study examines the effect of Mycoplasma pulmonis infection on the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the trigeminal ganglion and in the mucosa of the nose and trachea in rats. We compared germ-free (GF), conventionally raised (CV) and specific pathogen-free (SPF) rats. The concentrations of SP and CGRP in the nasal mucosa were assessed with immunohistochemistry, and their prohormonal transcripts in the trigeminal ganglion were assessed with Northern blot. Mucosa was also processed for light microscopy and electron microscopy. SP-like immunoreactivity was greater in the nasal mucosa of infected animals than in uninfected controls. CGRP-like immunoreactivity was greater in the nasal septum, but not in the nasal turbinate, of infected than uninfected animals. In contrast, no change was evident in the expression levels of the prohormonal transcripts in the trigeminal ganglion. Infected nasal and tracheal mucosa was oedematous and locally infiltrated with inflammatory cells. In the nose of uninfected GF rats, subepithelial lymphoid aggregations were scarce and appeared inactive. We conclude that Mycoplasma pulmonis infection results in increased immunoreactivity of substance P, probably within nerves. There was no clear evidence of increased synthesis of the precursors of substance P and calcitonin gene-related peptide.
Pancreatic protease-activated receptors: friend and foe
Authors: F. Gorelick
Journal: Gut (2007)

PAR2 activation may protect the acinar cell by enhancing secretion, but may still leave you in pain

Two regulatory elements of the exocrine pancreas, one new and one old, may interact to regulate previously undescribed physiological and pathological responses of the pancreas. The new targets are protease-activated receptors (PARs); the old elements are the serine proteases trypsin and tryptase, which are the most potent agonists of these G-protein-coupled receptors.1 The PAR family of G-protein-coupled receptors exhibits a distinct activation mechanism. Limited cleavage of the extracellular domain of PARs by serine proteases uncovers a peptide on the N-terminus that interacts with another extracellular region to activate the receptor. PAR isoforms exhibit a distinct tissue distribution and are selectively activated by specific classes of proteases. For example, the PAR2 isoform that is found in the pancreas on epithelial cells and nerves is selectively activated by trypsin and tryptase. While the role of the PAR2 in health and disease is currently being elucidated, recent studies have suggested that it might participate in pancreatic responses.

Previous findings by Nguyen et al 2 could be relevant to the effects of pancreatic PAR2 under physiological and pathological conditions. They showed that activation of the pancreatic ductal cell PAR2 by trypsin results in activation of electrolyte secretion. The enhanced chloride secretion was mediated by PAR2-dependent increases in cellular calcium. This study suggests that if activated trypsin was released from the pancreatic acinar cells (which might occur even with physiological stimulation), it could stimulate fluid and electrolyte secretion from small duct cells and help clear activated enzymes from the pancreatic duct. It could also function as a back-up mechanism should the major mechanism of ductal secretion, cystic fibrosis transmembrane conductance regulator, fail. This study found that PAR2 was localised to the basolateral membrane, and trypsin generated by …
Survival Effects of Postmastectomy Adjuvant Radiation Therapy Using Biologically Equivalent Doses: A Clinical Perspective
Authors: Val Gebski, Marivic Lagleva, Anthony Keech, John Simes, Allan O. Langlands
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Postmastectomy radiation therapy reduces locoregional recurrence among women with operable breast cancer, but whether it improves survival has been controversial. We reanalyzed the results from 36 unconfounded trials (i.e., addition of radiation therapy was the sole discriminant between treatments being compared) that were identified in previous meta-analyses, which provided 38 comparisons. Methods: We used three predefined treatment categories for individual patient data: 1) a biologically equivalent dose (BED) of 40–60 Gy in 2-Gy fractions with an appropriate target volume, 2) an inadequate or excessive dose of radiation therapy, and 3) an inappropriate target volume. Effects of radiation therapy on 5-year and 10-year survival in each of the treatment categories were estimated from a cohort of 13 199 patients from the published rates or, if these were unavailable, from the published survival curves. We also used this categorization to reanalyze data from Early Breast Cancer Trialists' Collaborative Group (EBCTCG) postmastectomy studies. At 10 years, 16 (84%) of the 19 comparisons in our study coincided with those reported by the EBCTCG. All statistical tests were two-sided. Results: Twenty-five of the 38 available comparisons had used optimal and complete radiotherapy (i.e., category 1). Of these 25 comparisons, 17 had 5-year data, and these data showed that adjuvant radiation therapy was associated with a 2.9% absolute increase in survival (odds ratio [OR] of death = 0.87, 95% confidence interval [CI] = 0.79 to 0.96; P = .006). Thirteen category 1 trials had data at 10 years, and these data showed that adjuvant radiation therapy was associated with a statistically significant 6.4% absolute increase in survival (OR of death = 0.78, 95% CI = 0.70 to 0.85; P <.001). No statistically significant change in survival was observed among category 2 (OR of death = 0.91, 95% CI = 0.75 to 1.11) or 3 (OR of death = 0.97, 95% CI = 0.61 to 1.55) trials. Among the 33 EBCTCG studies, odds of local recurrence were reduced more among category 1 trials (80% lower) than among category 2 (70% lower) or 3 (64% lower) trials ( Pheterogeneity <.001). Odds of all-cause death were also lower among category 1 trials (13% lower) than among category 2 (3% lower) or 3 (26% higher) trials ( Pheterogeneity = .01). Conclusions: Adjuvant radiation therapy with an optimal BED and target volume was statistically significantly associated with improved survival for up to 10 years.
THE RELATION OF THE KREBS CYCLE TO VIRAL SYNTHESIS
Authors: W. W. Ackermann
Journal: The Journal of Experimental Medicine (1951)

A further study has been made of the relationship of reactions of the Krebs cycle to the propagation of influenza virus. By the administration of sublethal doses of sodium fluoroacetate which were found to increase the concentration of citrate in the mouse lung, it was possible to demonstrate a blocking of the citric acid cycle in that organ. Further, the intraperitoneal administration of these concentrations of fluoroacetate was found to inhibit markedly the propagation of influenza, Type A, virus in the lungs of mice. The inhibition was observed when the fluoroacetate was administered 15 minutes, 6 hours, or 12 hours after the mice were inoculated with virus. This effect was also demonstrable when the concentration of the viral inoculum was varied over a range of virus titers from 10(3.5) to 10(6.5). Sodium fluoroacetate was found to have no effect in vitro on the infectivity or hemagglutinating property of the virus. The significance of these findings with regard to chemotherapy and to the mechanism of viral synthesis is described.
Prediction of the clinical course of COPD using the old and the new GOLD classification
Authors: Peter Lange, Jacob Louis Marott, Morten Dahl, Truls Sylvan Ingebrigtsen, Jørgen Vestbo, Børge Nordestgaard
Journal: European Respiratory Journal (2012)

Using data from The Copenhagen General Population Study and The Copenhagen City Heart Study comprising more than 50,000 individuals, we identified 6,628 persons older than 40 years of age with spirometrically defined COPD (FEV 1 /FVC ratio below 0.7 and no asthma). These individuals were subdivided according to the GOLD 2007 into stages 1, 2 3 and 4 (based on spirometry only) and according to the GOLD 2011 (using spirometry, mMRC-dyspnea scale and the number of exacerbations in the previous year) into stages A, B, C and D. They were followed for the subsequent year with regard to important COPD outcomes.   Conclusions:   1. The distribution of the individuals according to the two stratifications differs considerably  2. With regard to prediction of exacerbations, the A-D GOLD 2011 classification performes well  3. Compared with the group D, the lack of symptoms in group C is, not surprisingly, associated with lower frequency of treament with inhaled medications, but also with a sligthly higher frequency of exacerbations  4. Presence of dyspnea and a low level of FEV 1  are both predictors of high risk of hospitalisation/casualty ward visit due to COPD, whereas dyspnea seems to be a better predictor of all cause mortality than FEV 1 .
STUDIES ON THE AGENT OF INFECTIOUS HEPATITIS
Authors: Miles E. Drake, Charles Ward, Joseph Stokes, Werner Henle, George C. Medairy, Françoise Mangold, Gertrude Henle
Journal: The Journal of Experimental Medicine (1952)

At the onset of an epidemic in a closed institution about one-fourth of the inmates were skin-tested. During the year following the skin test, 5 cases of hepatitis with jaundice were recorded among 320 skin-tested individuals with unknown histories, one in the 144 skin test-positive, and 4 in the 176 skin test-negative subjects. In contrast 112 cases occurred among the 825 non-skin-tested individuals. Thus, the incidence of jaundice in the skin-tested group was 1.6 per cent as against 13.6 per cent in the non-skin-tested individuals. Possible explanations for this observation have been discussed.
Non-invasive cardiac stress testing before elective major non-cardiac surgery: population based cohort study
Authors: D. N Wijeysundera, W S. Beattie, P. C Austin, J. E Hux, A. Laupacis
Journal: BMJ (2010)

<b>Objective</b> To determine the association of non-invasive cardiac stress testing before elective intermediate to high risk non-cardiac surgery with survival and hospital stay. <b>Design</b> Population based retrospective cohort study. <b>Setting </b>Acute care hospitals in Ontario, Canada, between 1 April 1994 and 31 March 2004. <b>Participants</b> Patients aged 40 years or older who underwent specific elective intermediate to high risk non-cardiac surgical procedures. <b>Interventions</b> Non-invasive cardiac stress testing performed within six months before surgery. <b>Main outcome measures</b> Postoperative one year survival and length of stay in hospital. <b>Results</b> Of the 271 082 patients in the entire cohort, 23 991 (8.9%) underwent stress testing. After propensity score methods were used to reduce important differences between patients who did or did not undergo preoperative stress testing and assemble a matched cohort (n=46 120), testing was associated with improved one year survival (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.99; P=0.03) and reduced mean hospital stay (difference −0.24 days, 95% CI −0.07 to −0.43; P&lt;0.001). In an analysis of subgroups defined by Revised Cardiac Risk Index (RCRI) class, testing was associated with harm in low risk patients (RCRI 0 points: HR 1.35, 95% CI 1.05 to 1.74), but with benefit in patients who were at intermediate risk (RCRI 1-2 points: 0.92, 95% CI 0.85 to 0.99) or high risk (RCRI 3-6 points: 0.80, 95% CI 0.67 to 0.97). <b>Conclusions </b>Preoperative non-invasive cardiac stress testing is associated with improved one year survival and length of hospital stay in patients undergoing elective intermediate to high risk non-cardiac surgery. These benefits principally apply to patients with risk factors for perioperative cardiac complications.
Corneal Ectasia After Excimer Laser Keratorefractive Surgery: Histopathology, Ultrastructure, and Pathophysiology
Authors: Daniel G. Dawson, J. Bradley Randleman, Hans E. Grossniklaus, Terrence P. O'Brien, Sander R. Dubovy, Ingo Schmack, R. Doyle Stulting, Henry F. Edelhauser
Journal: Ophthalmology (2008)
Randomized Comparison of Distal Protection With a Filter-Based Catheter and a Balloon Occlusion and Aspiration System During Percutaneous Intervention of Diseased Saphenous Vein Aorto-Coronary Bypass Grafts
Authors: Gregg W. Stone, Campbell Rogers, James Hermiller, Robert Feldman, Patrick Hall, Robert Haber, A. Masud, Patrick Cambier, Ron P. Caputo, Mark Turco, Richard Kovach, Bruce Brodie, Howard C. Herrmann, Richard E. Kuntz, Jeffrey J. Popma, Steve Ramee, David A. Cox
Journal: Circulation (2003)

The high rate of periprocedural complications resulting from atherothrombotic embolization after percutaneous intervention in diseased saphenous vein grafts is reduced by distal microcirculatory protection using a balloon occlusion and aspiration system. Whether filter-based catheters, which offer the inherent advantages of maintained perfusion and ease of use, are as effective for this purpose has not been established.A total of 651 patients undergoing percutaneous intervention of 682 saphenous vein graft lesions were prospectively randomized to distal protection with the filter-based FilterWire EX versus the GuardWire balloon occlusion and aspiration system. Device success was 95.5% and 97.2% with the FilterWire EX and GuardWire, respectively (P=0.25). Postprocedural measures of epicardial flow and angiographic complications were similar between the 2 groups, although bailout IIb/IIIa inhibitors were required slightly less frequently in the FilterWire EX group (0% versus 1.5%, P=0.03). The primary end point, the composite incidence of death, myocardial infarction, or target vessel revascularization at 30 days, occurred in 9.9% of FilterWire EX patients and 11.6% of GuardWire patients (difference [95% CI]=-1.7% [-6.4%, 3.1%]; P for superiority=0.53, P for noninferiority=0.0008).Distal protection with the FilterWire EX may be safely used as an adjunct to percutaneous intervention of diseased saphenous vein grafts and, compared with distal protection with the GuardWire balloon occlusion and aspiration system, results in similar rates of major adverse cardiac events at 30 days.
Effects of unconditional and conditional cash transfers on child health and development in Zimbabwe: a cluster-randomised trial
Authors: Laura Robertson, Phyllis Mushati, Jeffrey W Eaton, Lovemore Dumba, Gideon Mavise, Jeremiah Makoni, Christina Schumacher, Tom Crea, Roeland Monasch, Lorraine Sherr, Geoffrey P Garnett, Constance Nyamukapa, Simon Gregson
Journal: The Lancet (2013)
Application of Transcription Factor “Decoy” Strategy as Means of Gene Therapy and Study of Gene Expression in Cardiovascular Disease
Authors: Ryuichi Morishita, Jitsuo Higaki, Naruya Tomita, Toshio Ogihara
Journal: Circulation Research (1998)

Abstract —Recent progress in molecular biology has provided new techniques for inhibiting target gene expression. In particular, the application of DNA technology, such as antisense strategy to regulate the transcription of disease-related genes in vivo, has important therapeutic potential. Recently, transfection of cis -element double-stranded oligodeoxynucleotides (ODNs), referred to as “decoy” ODNs, has been reported to be a powerful tool in a new class of anti-gene strategies for gene therapy and in the study of transcriptional regulation. Transfection of double-stranded ODNs corresponding to the cis sequence will result in the attenuation of authentic cis - trans interaction, leading to the removal of trans factors from the endogenous cis elements with subsequent modulation of gene expression. This “decoy” strategy is not only a novel strategy for gene therapy as an anti-gene strategy but also a powerful tool for the study of endogenous gene regulation in vivo as well as in vitro. In this article, we reviewed (1) the mechanisms and (2) the potential applications of decoy strategy.
Regulation of Cardiac L-Type Calcium Channels by Protein Kinase A and Protein Kinase C
Authors: Timothy J. Kamp, Johannes W. Hell
Journal: Circulation Research (2000)

Abstract —Voltage-dependent L-type Ca 2+ channels are multisubunit transmembrane proteins, which allow the influx of Ca 2+ ( I Ca ) essential for normal excitability and excitation-contraction coupling in cardiac myocytes. A variety of different receptors and signaling pathways provide dynamic regulation of I Ca in the intact heart. The present review focuses on recent evidence describing the molecular details of regulation of L-type Ca 2+ channels by protein kinase A (PKA) and protein kinase C (PKC) pathways. Multiple G protein–coupled receptors act through cAMP/PKA pathways to regulate L-type channels. β-Adrenergic receptor stimulation results in a marked increase in I Ca , which is mediated by a cAMP/PKA pathway. Growing evidence points to an important role of localized signaling complexes involved in the PKA-mediated regulation of I Ca , including A-kinase anchor proteins and binding of phosphatase PP2a to the carboxyl terminus of the α 1C (Ca v 1.2) subunit. Both α 1C and β 2a subunits of the channel are substrates for PKA in vivo. The regulation of L-type Ca 2+ channels by Gq-linked receptors and associated PKC activation is complex, with both stimulation and inhibition of I Ca being observed. The amino terminus of the α 1C subunit is critically involved in PKC regulation. Crosstalk between PKA and PKC pathways occurs in the modulation of I Ca . Ultimately, precise regulation of I Ca is needed for normal cardiac function, and alterations in these regulatory pathways may prove important in heart disease.
Inhibition of Na+-Dependent Transporters in Cystine-Loaded Human Renal Cells
Authors: Ibrahim C[COMBINING CEDILLA]Cetinkaya, Eberhard Schlatter, Jochen R. Hirsch, Peter Herter, Erik Harms, Robert Kleta
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Cystinosis is the most common cause of the renal Fanconi syndrome in children, leading to severe electrolyte disturbances and growth failure. A defective lysosomal transporter, cystinosin, results in intralysosomal accumulation of cystine. Loading cells with cystine dimethyl ester (CDME) is the only available model for this disease. This model was used to present electrophysiologic studies on immortalized human kidney epithelial (IHKE-1) cells that had been derived from the proximal tubule with the slow whole-cell patch clamp technique. Basal membrane voltages (Vm) of IHKE-1 cells were −30.7 ± 0.4 mV (n = 151). CDME concentration-dependently altered Vm with an initial depolarization (2.7 ± 0.2 mV;n = 76; 1 mM CDME) followed by a more pronounced hyperpolarization (−9.9 ± 1.0 mV;n = 49). Three Na+-dependent transporters were examined. Alanine (1 mM) depolarized IHKE-1 cells by 17.6 ± 0.7 mV (n = 59), and phosphate (1.8 mM) depolarized by 9.7 ± 1.1 mV (n = 18). Acidification of IHKE-1 cells with propionate (20 mM) resulted in a depolarization of Vm by 7.1 ± 0.3 mV (n = 21) followed by a repolarization by 2.9 ± 0.3 mV/min (n = 17), reflecting Na+/H+-exchanger activity. Acute addition of 1 mM CDME did not alter the alanine- and propionate-induced changes in Vm, but it reduced the phosphate-induced depolarization by 37 ± 9% (n = 10). Incubation with 1 mM CDME reduced the activity of all three transporters. Depolarizations by alanine and phosphate and the repolarization after propionate were inhibited by 57 ± 4% (n =30), 45 ± 9% (n = 9), and 78 ± 15% (n = 8), respectively. In conclusion, this study demonstrates that CDME acutely alters Vm of IHKE-1 cells and that at least three Na+-dependent transporters are inhibited, the Na+-phosphate cotransporter most sensitively. This might suggest that phosphate depletion and dissipation of the Na+-gradient are involved in the development of the Fanconi syndrome of cystinosis.