tbuckley/cabot-search huggingface dataset:
Quasispecies of hepatitis C virus in serum and in three different parts of the liver of patients with chronic hepatitis
Authors: Akito Sakai, Shuichi Kaneko, Masao Honda, Eiki Matsushita, Kenichi Kobayashi
Journal: Hepatology (1999)

Hepatitis C virus (HCV) has been known to infect hosts as a quasispecies. Several reports have shown this using serum samples, but there is little information about quasispecies in the liver. In this study, we evaluated quasispecies in serum and in 3 different parts of the liver in 8 patients with varying severity of chronic hepatitis C by calculating nucleotide diversity, entropy, type of substitution and by phylogenetic analysis. Nucleotide diversity of HCV was different in each sample and ranged from 0.37% +/- 0.31% to 4.10% +/- 1.06%. However, the degree of HCV diversity in serum correlated with that in the liver in each patient (P <.01). Common HCV clones were found both in serum and liver samples in all 6 noncirrhotic patients, but all serum clones were different from the clones from the 2 cirrhotic livers. Phylogenetic analysis showed that the degree of genetic diversity of HCV among the 3 liver samples was significantly high in the 4 patients with fibrosis. These genetic compartmentalizations of HCV did not depend on the type of substitution or the viral load of each liver sample. HCV quasispecies within the liver may be closely related to the viral life cycle and the pathogenesis of persistent infection of HCV.
NHS staff should inform patients of negligent acts
Authors: C. Dyer
Journal: BMJ (2003)

Doctors and managers in the NHS will be placed under a statutory “duty of candour” requiring them to tell patients when a negligent act or omission causes harm, under plans for sweeping reform of the clinical negligence system unveiled this week.

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Professor Liam Donaldson's report calls for candour 

Credit: MARK THOMAS

A new NHS “redress scheme” will offer a compensation package of remedial care, apologies, and compensation up to £30 000 ($49 670; €43 170) without the need for litigation, and no-fault compensation for babies with severe birth related neurological damage. The redress scheme, to be administered by a new …

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Computation of regurgitant Effective Orifice Area (EOA) using digital 3-D reconstruction of multithreshold velocities from the flow convergence region: an in vitro study using dynamically changing orifices mimicking mitral valve prolapse
Authors: Xiaokui Li, Jun Li, Jinfeng Xu, Ghada O.M. El-Sedfy, Xiang-Ning Li, David J. Sahn
Journal: Journal of the American College of Cardiology (2002)
Mutant ftsI genes in the emergence of penicillin-binding proteinmediated β-lactam resistance in Haemophilus influenzae in Norway
Authors: D. Skaare, A.-G. Allum, I.L. Anthonisen, A. Jenkins, A. Lia, L. Strand, Y. Tveten, B.-E. Kristiansen
Journal: Clinical Microbiology and Infection (2009)
PROSTATECTOMY, THE METHOD OF CHOICE IN THE MANAGEMENT OF PROSTATIC OBSTRUCTION.
Authors: EUGENE FULLER
Journal: JAMA (1901)

Prostatic hypertrophy, directly or indirectly, is the cause of death in such a large proportion of elderly men that the question of its surgical management is one of the greatest importance. In the case of most individuals who so die at the present time no serious attempt is made to save life. The community at large is not as yet educated beyond the idea of the catheter, and the same, I am sorry to say, can almost be said of the medical profession. A few years ago a person could die of appendicitis in the absence of surgical treatment and no adverse comment would be provoked by the event. Now, however, such a happening is regarded by the sensible portion of the community much as is the death of a person under faith-cure treatment, and no physician who is careful of his reputation fails at least to raise the question
Abstract LB-229: PTEN modulates EGFRvIII-mediated SHP-2 activation and translocation to affect glioblastoma sensitivity to tyrosine kinase inhibitors (TKI)
Authors: Gurpreet Singh Kapoor, Donald M. O'Rourke
Journal: Cancer Research (2010)

Abstract EGFRvIII, a constitutively active truncated mutant of epidermal growth factor receptor (EGFR), has been associated with increase neoplastic transformation and poor overall survival (OS). An earlier report showed that expression of EGFRvIII in gliomas provides resistance to chemotherapy. Co-expression of EGFRvIII and PTEN in a small subset of recurrent GBMs has been shown to increase sensitivity to tyrosine kinase inhibitors (TKI), including Erlotinib (tarceva) and Geftinib. However, the exact mechanism of EGFRvIII and PTEN interaction in response to TKI is still unresolved. Our recent reports showed that SHP-2 PTPase and its phosphatase activity are required for the EGFRvIII-mediated transformation. The aim of the present work was to investigate the molecular interaction between EGFRvIII/SHP-2 activation complex and PTEN in response to tarceva treatment and its effect on glioblastoma transformation. Our recent report demonstrated an increased SHP-2 phosphorylation in U87MG. EGFRvIII (PTEN-deficient) when compared to PTEN-intact LN229.EGFRvIII cells. In the present study, we show that tarceva treatment abolished EGFRvIII, EGFR, SHP-2 and Erk1/2, but Src family kinase (SFK), phosphorylation in LN229.EGFRvIII cells at all time intervals ranging from 30 minutes to 6 hours. On the contrary, phosphorylation of EGFRvIII, Src and Erk1/2 in U87MG. EGFRvIII cells was inhibited in early time points, but was restored in 2 to 6 hours. Surprisingly, phosphorylation of SHP-2 at Tyr542 residue was unaffected by tarceva treatment, but EGFR phosphorylation was inhibited in a time-dependent manner. PTEN deficiency resulted in resistance to tarceva treatment as assessed by MTT proliferation and soft agar transformation assays. Immunofluorescent labeling of U87MG. EGFRvIII cells with anti-phospho-SHP-2 (Tyr542) antibody showed perinuclear localization of SHP-2, whereas LN229.EGFRvIII cells exhibited membrane staining of phosphorylated SHP-2 (Tyr542). Our results showed that tarceva increased perinuclear SHP-2 Tyr542 in U87MG. EGFRvIII cells. Interestingly, stable expression of PTEN in U87MG. EGFRvIII cells conferred relocalization of phospho-SHP-2 to the membrane, a phenotype resembling LN229.EGFRvIII cells. Moreover, PTEN-expressing U87MG. EGFRvIII clones grew slower and showed a partially untransformed phenotype. These results suggest that SHP-2 is downstream effectors of PTEN and that PTEN deficiency may lead to SHP-2 activation and perinuclear localization by EGFRvIII, which may results in increased resistance to TKIs. Therefore, targeting SHP-2 may provide a new and effective therapeutic approach for treatment of glioblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-229.
Acoustic Assessment of the Physical Integrity of Bjo¨rk-Shiley Convexo-Concave Heart Valves
Authors: J.J. Dow, Terry D. Plemons, Kent Scarbrough, Hugh Reeder, Mike Hovenga, David W. Wieting, James G. Chandler
Journal: Circulation (1997)

Background Several lines of evidence indicate a two-stage failure mode for the Bjo¨rk-Shiley convexo-concave (C/C) heart valve, in which one of the two outlet strut legs separates from the flange before the other, potentially providing an opportunity to identify and prophylactically replace failure-prone valves. Radiographic single leg separation (SLS) detection, although successful, is subjective and skill intensive, implying a need for both an objective preliminary screen and subsequent corroboration of the radiographic findings. Methods and Results We developed a time-windowed, power density analysis of C/C valve closing sounds to detect the vibrational resonance that characterizes the presence of an intact outlet strut in clinically functioning, 29-mm-flange size C/C valves. Recordings from more than 800 patients enrolled in radiographic SLS detection studies were analyzed, and the assessment algorithm was evaluated through a blinded test of 32 study valves for which the true status became known consequent to an autopsy or surgical explantation. Valves were objectively scored on a 0-to-1 scale, with 1 being assuredly intact and scores of &lt;0.50 indicating a probable SLS. All except five valves (incorrectly designated probable SLS) were classified correctly, for a sensitivity of 1.00 (95% confidence interval, 0.79 to 1.00) and a specificity of 0.69 (0.41 to 0.89). Conclusions This level of accuracy is sufficient to serve as an effective preliminary screen, potentially allowing a threefold concentration of SLS prevalence among the C/C valves of patients undergoing radiographic assessment. The value of acoustic classification in avoiding unnecessary operations prompted by false-positive radiographs is less certain.
820-3 Nonhigh-density lipoprotein cholesterol per national cholesterol education panel and advanced lipoprotein analysis: Correlation and relationship to premature coronary artery disease
Authors: Kwame Osei Akosah, Ana Mari Schaper, Vicki Lynn McHugh, Sharon Ione Barnhart, Patricia A Perlock, Troy Anthony Haider, Michelle Ann Mathiason
Journal: Journal of the American College of Cardiology (2004)
COMMENT BY DR. GOULD.
Authors: Geo. M. Gould
Journal: JAMA (1902)

Philadelphia, Nov. 6, 1902. <h3>To the Editor:</h3> —In reference to the courteous note of Dr. Hale I would say that in my opinion: The best method of retinoscopy, when carried out by the most expert, is not trustworthy when subjective methods are possible with intelligent people. No method of retinoscopy is accurate, not even the best one, except under cycloplegia. The Germans do not use cycloplegia. The only use of retinoscopy advocated in my paper was for children. The Germans do not refract little children of from 2 to 6 years of age. The great value of refraction is to diagnose and correct astigmatism. The Germans do not diagnose, correct or care for astigmatism, at least in those minor degrees, which produce the greatest eyestrain. The method of retinoscopy used by the Germans is the old-fashioned one of Cuignet, which is utterly inaccurate and untrustworthy. The new method of Thorington,
Global Screening of Human Cord Blood Proteomes for Biomarkers of Toxic Exposure and Effect
Authors: David R. Colquhoun, Lynn R. Goldman, Robert N. Cole, Marjan Gucek, Malini Mansharamani, Frank R. Witter, Benjamin J. Apelberg, Rolf U. Halden
Journal: Environmental Health Perspectives (2008)

Exposures of pregnant women to natural and manmade chemicals can lead to negative health effects in the baby, ranging from low birth weight to developmental defects. In some cases, diseases were postulated to have their basis in toxic exposure in utero or in early childhood. Therefore, an understanding of fetal responses to environmental exposures is essential. To that end, cord blood is a readily accessible biofluid whose proteomic makeup remains mostly unexplored when compared with that of adults.Our goal was an initial global assessment of the fetal serum proteome and for the identification of protein biomarkers indicative of toxic in utero exposures related to maternal cigarette smoking.Drawing from a repository of 300 samples, we selected umbilical cord blood sera from 12 babies born to six smokers and six nonsmokers and analyzed both sample pools by tandem mass spectrometry in conjunction with isobaric tags (iTRAQ) for protein quantification.We identified 203 proteins, 17 of which were differentially expressed between the cigarette smoke-exposed and control populations. Most of the identified candidate biomarkers were biologically plausible, thereby underscoring the feasibility of screening neonates with global proteomic techniques for biomarkers of exposure and early biological effects triggered by in utero chemical exposures.This validation study provides an initial view of the proteome of human cord blood sera; it demonstrates the feasibility of identifying therein by use of proteomics, biomarkers of environmental, toxic exposures.
Use of Electroanatomic Mapping to Delineate Transseptal Atrial Conduction in Humans
Authors: Franz X. Roithinger, Jie Cheng, Arne SippensGroenewegen, Randall J. Lee, Leslie A. Saxon, Melvin M. Scheinman, Michael D. Lesh
Journal: Circulation (1999)

Background —Interaction between wave fronts in the right and left atrium may be important for maintenance of atrial fibrillation, but little is known about electrophysiological properties and preferential routes of transseptal conduction. Methods and Results —Eighteen patients (age 44±12 years) without structural heart disease underwent right atrial electroanatomic mapping during pacing from the distal coronary sinus (CS) or the posterior left atrium. During distal CS pacing, 9 patients demonstrated a single transseptal breakthrough near the CS os, 1 patient in the high right atrium near the presumed insertion of Bachmann’s bundle and 1 patient near the fossa ovalis. The mean activation time from stimulus to CS os was 48±15 ms compared with 86±15 ms to Bachmann’s bundle insertion ( P &lt;0.01) and 59±23 ms to the fossa ovalis ( P =NS and P &lt;0.01, respectively). During left atrial pacing, the earliest right atrial activation was near Bachmann’s bundle in 5 and near the fossa ovalis in 4 patients. The activation time from stimulus to CS os was 70±15 ms compared with 47±16 ms to Bachmann’s bundle ( P &lt;0.01) and 59±25 ms to the fossa ovalis ( P =NS). Whereas the total septal activation time was not significantly different during CS pacing compared with left atrial pacing (41±16 versus 33±17 ms), the total right atrial activation time was longer during CS pacing (117±49 versus 79±15 ms; P &lt;0.05). Conclusions —Three distinct sites of early right atrial activation may be demonstrated during left atrial pacing. These sites are in accord with anatomic muscle bundles and may have relevance for maintenance of atrial flutter or fibrillation.
Identification of serine protease as a major allergen of <i>Curvularia lunata</i>
Authors: R. Gupta, V. Sharma, S. Sridhara, B. P. Singh, N. Arora
Journal: Allergy (2004)

Background: Several proteins from Curvularia lunata have been identified as important fungal allergens. It will be worthwhile to study the functional aspects of these allergens. The present study aimed at purifying a major allergen and determining its biological function. Methods: Concanavalin A and Superdex 75 were used to purify Cur l 1 major allergen from C. lunata . Cur l 1 activity was determined qualitatively and quantitatively. Serine protease inhibitors and specific substrate was used to determine the biological function of the protein. Results: Concanavalin A‐bound fraction showed five allergenic proteins, which on Superdex G‐75 purification gave a homogenous Cur l 1 protein. Cur l 1 showed IgE reactivity with 80% of the C. lunata hypersensitive patient's sera indicating it to be a major allergen. It showed protease activity on different substrates. Cur l 1's amino terminal sequence, GLTQKSAPWGLGADTIVAVELDSY, showed homology with the alkaline serine protease precursor. Phenylmethylsulfonylfluoride, pefabloc, aprotinin and leupeptin inhibited 70–80% enzymatic activity of Cur l 1 and no inhibition was observed with ethylenediaminetetraacetic acid (EDTA). A dose‐dependent hydrolysis of N α ‐benzoyl‐ l ‐arginine ethyl ester‐hydrochloride, a specific serine protease substrate was obtained with Cur l 1. Conclusion: A major glycoprotein allergen Cur l 1 was purified to homogeneity from C. lunata . Amino terminal sequence and biochemical assays identified it as a serine protease.
Keep politics out of it
Authors: Fiona Godlee
Journal: BMJ (2005)

Are complementary and alternative medicines cost effective? Patients are increasingly voting with their feet, despite having to pay out of their own pockets, so governments and health plans must decide whether these treatments should be provided alongside conventional health care. The much leaked and now somewhat improved Smallwood report concludes that they should be funded, arguing that they will help patients and save money. In their editorial (p 856) Trevor Thompson and Gene Feder are perplexed about some aspects of the report—in particular the inclusion of asthma as one of the “effectiveness gaps” of conventional medicine. But overall they conclude that …
59 COMPARISON OF TWO QUANTITATIVE HCV RNA ASSAYS IN SAMPLES FROM PATIENTS TREATED WITH A PROTEASE INHIBITOR-BASED THERAPY: IMPLICATIONS FOR RESPONSE GUIDED THERAPY
Authors: B. Fevery, S. Susser, O. Lenz, G. Cloherty, D. Perner, G. Picchio, C. Sarrazin
Journal: Journal of Hepatology (2012)
HLA Matching and Cardiac Transplantation
Authors: Peter J. Morris
Journal: New England Journal of Medicine (1994)

The time constraints of cardiac transplantation -- namely, the need to implant the donor organ within four hours of its removal -- have prevented cardiac surgeons from considering prospective HLA matching of the donor and recipient, even if they thought it worthwhile. Several retrospective, single-center reports over the past six years suggest that there are fewer episodes of rejection and better graft survival among recipients of a well-matched heart110. In general, compatibility for the HLA-DR locus had the greatest influence on graft outcome, as first noted many years previously for kidney transplantation11 and confirmed in large cohorts of . . .
STEVOR Is a Plasmodium falciparum Erythrocyte Binding Protein that Mediates Merozoite Invasion and Rosetting
Authors: Makhtar Niang, Amy Kristine Bei, Kripa Gopal Madnani, Shaaretha Pelly, Selasi Dankwa, Usheer Kanjee, Karthigayan Gunalan, Anburaj Amaladoss, Kim Pin Yeo, Ndeye Sakha Bob, Benoit Malleret, Manoj Theodore Duraisingh, Peter Rainer Preiser
Journal: Cell Host & Microbe (2014)
Modern Methods in the History of Medicine
Authors: Lester S. King
Journal: JAMA (1971)

Anyone who believes that medical history is a pedantic subject existing apart from the mainstreams of "progress" should read this new book. It will introduce him to the array of disciplines that converge on medical history as it is now being studied. Pitiable indeed is the physician who cannot thrill to at least some of the subjects discussed therein. In the volume are 21 essays which in the aggregate cover a vast range. They extend from the history of ideas—medicine as part of intellectual history—to the techniques of actual experimentation which have been found useful in solving particular historical problems—what Professor Clarke calls "practical history." And in between we find a spectrum of relevant topics such as demography and medical geography, biology and palaeopathology, statistics, automation, computer technology, social medicine, conventional historical research and evaluation of evidence, biographical studies, the new oral history, some problems of libraries and of teaching,
Unopposed Neutrophil Elastase in Bronchoalveolar Lavage from Transplant Recipients with Cystic Fibrosis
Authors: D. NUNLEY, J. DAUBER, A. IACONO, R. KEENAN, A. ZEEVI, R. CORNWELL, R. LOVE, K. MEYER, Paula Soergel, Kimberly Peterson
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Large numbers of neutrophils with unopposed neutrophil elastase (NE) proteolytic activity are found in lower respiratory tract secretions from most patients with advanced cystic fibrosis (CF). To determine whether antielastase defenses may be overwhelmed in epithelial lining fluid after lung transplantation, we measured NE activity (cleavage of the specific substrate, MeO-Suc-Ala-Ala-Pro-Val-pNA) in bronchoalveolar lavage fluids (BALF) obtained for surveillance or diagnostic purposes at various intervals (1 mo to 7 yr after transplantation) from 52 recipients who had undergone double or bilateral lung transplantation for end-stage CF. Unopposed NE activity was found in BALF from 14 recipients, most of whom also had ⩾ 105 colony forming units (cfu) of Pseudomonas aeruginosa in BALF. Ten of the 14 recipients with unopposed NE in bronchoalveolar lavage (BAL) had developed obliterative bronchiolitis (OB), but only 8 of the 38 subjects without unopposed NE activity had OB (p = 0.002; Fisher exact test). We conclude that antiprotease defenses in lower respiratory tract secretions of CF patients receiving lung allografts are sufficient in the majority of patients to prevent unopposed NE activity. However, the presence of unopposed NE activity in BAL from lung allografts of patients with CF is associated with progressive, irreversible OB and graft failure.
Acat1 Knockdown Gene Therapy Decreases Amyloid-β in a Mouse Model of Alzheimer's Disease
Authors: Stephanie R Murphy, Catherine CY Chang, Godwin Dogbevia, Elena Y Bryleva, Zachary Bowen, Mazahir T Hasan, Ta-Yuan Chang
Journal: Molecular Therapy (2013)

Both genetic inactivation and pharmacological inhibition of the cholesteryl ester synthetic enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1) have shown benefit in mouse models of Alzheimer's disease (AD). In this study, we aimed to test the potential therapeutic applications of adeno-associated virus (AAV)-mediated Acat1 gene knockdown in AD mice. We constructed recombinant AAVs expressing artificial microRNA (miRNA) sequences, which targeted Acat1 for knockdown. We demonstrated that our AAVs could infect cultured mouse neurons and glia and effectively knockdown ACAT activity in vitro. We next delivered the AAVs to mouse brains neurosurgically, and demonstrated that Acat1-targeting AAVs could express viral proteins and effectively diminish ACAT activity in vivo, without inducing appreciable inflammation. We delivered the AAVs to the brains of 10-month-old AD mice and analyzed the effects on the AD phenotype at 12 months of age. Acat1-targeting AAV delivered to the brains of AD mice decreased the levels of brain amyloid-β and full-length human amyloid precursor protein (hAPP), to levels similar to complete genetic ablation of Acat1. This study provides support for the potential therapeutic use of Acat1 knockdown gene therapy in AD.
Interplay between Cytosolic Dopamine, Calcium, and α-Synuclein Causes Selective Death of Substantia Nigra Neurons
Authors: Eugene V. Mosharov, Kristin E. Larsen, Ellen Kanter, Kester A. Phillips, Krystal Wilson, Yvonne Schmitz, David E. Krantz, Kazuto Kobayashi, Robert H. Edwards, David Sulzer
Journal: Neuron (2009)
MULTIVESSEL VERSUS CULPRIT-ONLY PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH MULTIVESSEL DISEASE AND ST-ELEVATION MYOCARDIAL INFARCTION COMPLICATED WITH CARDIOGENIC SHOCK
Authors: Bimmer Claessen, Marije M. Vis, Karel T. Koch, Jan Baan, Martijn Meuwissen, Rob J. de Winter, Jan G. Tijssen, Jan J. Piek, Jose P. Henriques
Journal: Journal of the American College of Cardiology (2010)
Rare and low-frequency coding variants in CXCR2 and other genes are associated with hematological traits
Authors: Paul L Auer, Alexander Teumer, Ursula Schick, Andrew O'Shaughnessy, Ken Sin Lo, Nathalie Chami, Chris Carlson, Simon de Denus, Marie-Pierre Dubé, Jeff Haessler, Rebecca D Jackson, Charles Kooperberg, Louis-Philippe Lemieux Perreault, Matthias Nauck, Ulrike Peters, John D Rioux, Frank Schmidt, Valérie Turcot, Uwe Völker, Henry Völzke, Andreas Greinacher, Li Hsu, Jean-Claude Tardif, George A Diaz, Alexander P Reiner, Guillaume Lettre
Journal: Nature Genetics (2014)