tbuckley/cabot-search huggingface dataset:
Eosinophil leukocyte degranulation in response to serum‐opsonized beads: C5a and platelet‐activating factor enhance ECP release, with roles for protein kinases A and C
Authors: A. Egesten, J. Malm
Journal: Allergy (1998)

Background Eosinophils have a typical content of granule‐bound, cytotoxic, cationic proteins which may. when released to the external milieu, play roles i n diseases such as asthma and parasitic infestation. Therefore, we have investigated possible mechanisms by which their release is regulated in eosinophils. Methods The enzyme‐linked immunosorhent assay (ELISA) was used to detect released eosinophil cationic protein (ECP). Release of ECP was induced by serum‐opsonized, nonphagocytosable Sephadex beads (SOS). Results The complement fragment C5a and platelet‐activating factor (PAF) were found to enhance ECP release in response to SOS in a dose‐dependent fashion, and, contrary to previous reports, they were not found to act as secretagogues themselves on eosinophils in suspension. The role of protein kinase C (PKC) in eosinophil degranulation has been controversial. We found that ECP release induced by SOS was inhibited by the PKC inhibitors staurosporine and calphostin C. Activation of protein kinase A (PKA). by raising cAMP, also inhibited ECP release. Furthermore, pertussis toxin decreased ECP release on opsonized beads, indicating the involvement of pertussis‐toxin‐sensitive G proteins. Conclusions C5a. and PAF enhance granule release, rather than acting as secretagogues themselves. PKC and PKA have opposing roles in the regulation of ECP release in response to SOS.
Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs)
Authors: Yves Lepelletier, Raphaël Zollinger, Cristina Ghirelli, Françoise Raynaud, Réda Hadj-Slimane, Antonio Cappuccio, Olivier Hermine, Yong-Jun Liu, Vassili Soumelis
Journal: Blood (2010)
Individualized Guidelines: The Potential for Increasing Quality and Reducing Costs
Authors: David M. Eddy, Joshua Adler, Bradley Patterson, Don Lucas, Kurt A. Smith, Macdonald Morris
Journal: Annals of Internal Medicine (2011)

Background: Current guidelines focus on a particular risk factor and specify criteria for categorizing persons into a small number of treatment groups. Objective: To compare current guidelines with individualized guidelines (that use readily available characteristics from each person to calculate the risk reduction expected from treatment and to identify persons for treatment in ranked order of decreasing expected benefit), in the context of blood pressure management. Design: Analysis of person-specific, longitudinal data. Setting: The ARIC (Atherosclerosis Risk in Communities) Study. Participants: Persons aged 45 to 64 years without preexisting cardiovascular disease who currently do not receive antihypertensive treatment. Intervention: Treatment according to the criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 guidelines); individualized guidelines, or treatment in decreasing order of expected benefit; and random care, or treatment of persons selected at random. Measurements: Number of myocardial infarctions (MIs) and strokes and medical costs. Results: Compared with treating people according to random care, individualized guidelines could prevent the same number of MIs and strokes as JNC 7 guidelines at savings that are 67% greater than using JNC 7 guidelines, or it could prevent 43% more MIs and strokes for the same cost as treatment according to JNC 7 guidelines. The superiority of individualized guidelines was not sensitive to a wide range of assumptions about costs, treatment effectiveness, level of risk for cardiovascular disease in the population, or effects on workflow. The degree of superiority was sensitive to the accuracy of the method used to rank patients and to its span (the proportion of the population for whom all of the outcomes of interest can be calculated). Limitations: Specific results apply to the effects of blood pressure management on MI and stroke in the ARIC Study population. The methods for calculating individual benefits require quantitative evidence about the relationships among risk factors, long-term outcomes, and treatment effects. Conclusion: Use of individualized guidelines can help to increase the quality and reduce the cost of care. Primary Funding Source: None.
867. Use of AAV Display Libraries to Generate Myotropic Vectors
Authors: Yu-Hung Kuo, Justin Fraser, Michael G. Kaplitt
Journal: Molecular Therapy (2005)

Adeno associated virus (AAV) has been quite successfully adapted as a gene therapy vector and is currently in clinical trials for a variety of disorders. The AAV family includes multiple serotypes that vary in capsid amino acid composition, resulting in different profiles of target tropism. As the number of different serotypes have expanded, so have the number of potential therapeutic targets for AAV based treatment. However, identifying and screening novel serotypes is not an efficacious strategy for generating de novo vectors with high target specificity. By chimerizing the serotype AAV1 and AAV2 capsids, we are able to delineate the surface domains which play a critical role in regulating vector efficacy. While chimerized vectors include the sequences necessary for binding to the primary receptor for AAV2, heparin, conferring heparin-binding to AAV1 alone is insufficient to recapitulate the target profile of AAV2. Our studies further demonstrate restrictions in the combinations of capsid surface amino acids. Therefore, capsid modification must take into consideration both primary receptor targeting as well as effects on viral formation and function. Prior attempts to retarget using display libraries have inserted random peptide sequences at permissible sites in the capsid. We opted instead to modify the AAV1 capsid by directly substituting a nonapeptide sequence centered on the heparin binding site. The library was screened against non-permissive cell lines resulting in two novel vectors. Clone DL2 bound heparin and its activity could be blocked by competition with heparin whereas DL1 has no heparin affinity. When compared to wild type AAV1 and AAV2, both clones have unique patterns of cellular tropism. Efficacy was enhanced for both above that of wild type AAV1 from which the library was created. Interestingly, when the novel nonapeptide sequences were placed into an AAV2 backbone, recombinant particles could be generated with equal efficacy as AAV2, but the particles were nonfunctional, providing further evidence of restrictions to capsid sequence combinations. As the in vitro data suggests that DL1 and DL2 are both significantly more efficient at transducing a myoblasts than wild type AAV the clones were tested in vivo by directly injecting muscle. When assayed for transgene activity 6 weeks later, DL2 showed markedly greater activity than both wild type viruses and DL1. Thus, our studies demonstrate the capability of substitutive display libraries to generate novel AAV based vectors for gene therapy with greater efficacy and more restricted tropism.
Health Sciences Libraries in the United States, 1969 to 1979
Authors: Susan Crawford
Journal: JAMA (1981)

<h3>Trends Affecting Libraries</h3> Beginning with the Second World War and continuing to the present, national health expenditures in the United States have increased at a steady and unprecedented rate. By 1978, health expenditures had reached an estimated $192.4 billion, or $863 per capita. The magnitude of these figures is underscored when we view them as percentages of the gross national product—9.1% in 1978, as compared with 6.8% ten years earlier.<sup>1</sup>Compiled by the US Health Care Financing Administration, these data include the total national expenditures for both public and private health services and supplies, for research and for medical facilities. The subsequent burgeoning of health-related activities has led to severe discontinuities, which, in concert with other changes, have challenged the library-based, biomedical communication system.<sup>2</sup> First, the great increase in volume of information and records has generated problems in identification of information, storage of publications, and delivery of documents.
North-south divide in social inequalities in Great Britain: Authors' reply
Authors: Tim Doran, Frances Drever, Margaret Whitehead
Journal: BMJ (2004)

EDITOR—The message we hoped readers would take from our paper is that the United Kingdom has large health inequalities in terms of social class, geography, and geography within the social class inequalities. We therefore concur with Bland's analysis, as his figures confirm this point. The differences between regions within each social class, although smaller than the differences between the social …
THE OPERATIVE TREATMENT OF EXTRA-UTERINE PREGNANCY AT OR NEAR TERM, WITH REPORT OF A CASE.Read before the Illinois State Medical Society, May 20, 1891.
Authors: CHRISTIAN FENGER
Journal: JAMA (1891)

It is not my intention in this paper to give an exhaustive exposé of all the details and the questions that arise in late extra-uterine pregnancy, but merely in connection with a case of this kind, which terminated fatally, to describe the thoughts and reflections that presented themselves to me in connection with the case. I shall, then, first describe the case, the different methods of operation and their prognoses, and later, review the more important points in the management of such cases from my own experience and from the literature as far as I have been able to obtain it. <i>Case.</i>—Mrs. C, 34 years of age, married thirteen years. Healthy as a child; first menstruated at the age of 14; always regular; three days' duration; for the past ten years two days only; never very abundant. A slight leucorrhœa for a few days following menstruation. Married at 21; a
Pharmacological Inhibition of KIT Activates MET Signaling in Gastrointestinal Stromal Tumors
Authors: Noah A. Cohen, Shan Zeng, Adrian M. Seifert, Teresa S. Kim, Eric C. Sorenson, Jonathan B. Greer, Michael J. Beckman, Juan A. Santamaria-Barria, Megan H. Crawley, Benjamin L. Green, Ferdinand Rossi, Peter Besmer, Cristina R. Antonescu, Ronald P. DeMatteo
Journal: Cancer Research (2015)

Abstract Gastrointestinal stromal tumors (GIST) are the most common adult sarcomas and the oncogenic driver is usually a KIT or PDGFRA mutation. Although GISTs are often initially sensitive to imatinib or other tyrosine kinase inhibitors, resistance generally develops, necessitating backup strategies for therapy. In this study, we determined that a subset of human GIST specimens that acquired imatinib resistance acquired expression of activated forms of the MET oncogene. MET activation also developed after imatinib therapy in a mouse model of GIST (KitV558del/+ mice), where it was associated with increased tumor hypoxia. MET activation also occurred in imatinib-sensitive human GIST cell lines after imatinib treatment in vitro. MET inhibition by crizotinib or RNA interference was cytotoxic to an imatinib-resistant human GIST cell population. Moreover, combining crizotinib and imatinib was more effective than imatinib alone in imatinib-sensitive GIST models. Finally, cabozantinib, a dual MET and KIT small-molecule inhibitor, was markedly more effective than imatinib in multiple preclinical models of imatinib-sensitive and imatinib-resistant GIST. Collectively, our findings showed that activation of compensatory MET signaling by KIT inhibition may contribute to tumor resistance. Furthermore, our work offered a preclinical proof of concept for MET inhibition by cabozantinib as an effective strategy for GIST treatment. Cancer Res; 75(10); 2061–70. ©2015 AACR.
Female sterilisation--no more tubal coagulation.
Authors: M Sutton, R de Vere
Journal: BMJ (1980)

The use of clips was discussed as a simple method of sterilization in the lead articles of April 12 (p. 1037) and May 10 (p. 1154). We have used the Hulka-Clemens clips as a method of choice for laparoscopic sterilization in Westminster Hospital since 1977, and have been impressed with their operative safety. However, recently we have had an alarming number of pregnancies occurring after clip sterilizations, and so have analyzed our figures. During the years April 1977-April 1980, 328 laparoscopic sterilizations were performed in this unit. Of these women, 8 to date have become pregnant, and showed tubal patency on hysterosalpingogram. All 9 failures occurred following use of the Hulka-Clemens clips. This gives an overall failure rate of 2.1% and a failure rate for clip sterilization estimated at 3%. In none of the failures was the sterilization performed with a termination or in the puerperium. In all the cases except 1, the clips were applied by a consultant or senior registrar. All the patients had a subsequent salpingectomy, and the tubes were inspected macroscopically and microscopically. In all cases, the clips were found to be properly applied across the fallopian tube and fully closed. Nevertheless, on microscopy, each case had a patent lumen present in at least 1 tube. We are unable to identify any elements in technique of application that could account for these failures; in 2 of the cases which failed, 2 Hulka-Clemens clips had been applied to each tube. We feel that these figures should be publicized, as strong views have been expressed in recent months condemning tubal diathermy as a sterilization method, and advocating the use of clips or rings because of easier reversibility. In our practice, clip sterilization is less safe than oral contraception or the IUD. We would be interested in hearing about similar failure rates in other units.
TCT-292 Identification of culprit carotid plaques in patients with ischemic stroke with a new noninvasive method
Authors: Georgios Benetos, Konstantinos Toutouzas, Christina Deligianni, Andreas Synetos, Maria Drakopoulou, Andreas Katsaros, Konstantinos Stathogiannis, Elias Siores, Kostas Spengos, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2014)
MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation
Authors: Elenoe C. Smith, Jonathan N. Thon, Matthew T. Devine, Sharon Lin, Vincent P. Schulz, Yanwen Guo, Stephanie A. Massaro, Stephanie Halene, Patrick Gallagher, Joseph E. Italiano, Diane S. Krause
Journal: Blood (2012)
Persistent Common Atrioventricular Canal
Authors: R. W. M. FRATER
Journal: Circulation (1965)

The mitral valve anatomy of endocardial cushion defects is reviewed and compared with the anatomic requirements for normal mitral valve function. It is shown that very often mitral valve anatomy is such that function should be not at all or only minimally affected. Evidence is quoted that this is indeed so. The potential harm that may result from indiscriminate suturing of mitral valve clefts and careless repair of the septal defects is described. Principles for the repair of the mitral valve in these cases are enunciated. A small series of cases that have had preoperative and 1-year postoperative assessments of mitral valve function is presented to illustrate some of these points.
Magnetic Resonance Imaging/Ultrasound–Fusion Biopsy Significantly Upgrades Prostate Cancer Versus Systematic 12-core Transrectal Ultrasound Biopsy
Authors: M. Minhaj Siddiqui, Soroush Rais-Bahrami, Hong Truong, Lambros Stamatakis, Srinivas Vourganti, Jeffrey Nix, Anthony N. Hoang, Annerleim Walton-Diaz, Brian Shuch, Michael Weintraub, Jochen Kruecker, Hayet Amalou, Baris Turkbey, Maria J. Merino, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: European Urology (2013)
Double blind, placebo controlled trial of betamethasone nasal drops for nasal polyposis.
Authors: R Chalton, I Mackay, R Wilson, P Cole
Journal: BMJ (1985)

would be greater than on the softer surface of fells, and were absent during cycling when passive contraction of the psoas would produce less colonic compression.This mechanism may be similar to the repeti- tive mechanical trauma described to explain contusion of the bladder and haematuria in runners.5 "Jogger's trots" is a further example of the many hazards that face marathon runners.Although our patient's symptoms may be controlled with drugs, this seems contrary to the principle of guidelines for the control of abuse of drugs in sport.We thank Mrs S Lamb for secretarial help.
Silicosis presenting as bilateral hilar lymphadenopathy.
Authors: D R Baldwin, L Lambert, C F Pantin, K Prowse, R B Cole
Journal: Thorax (1996)

Classical radiographic features of patients presenting with silicosis are diffuse interstitial shadowing with subsequent enlargement of hilar nodes, sometimes with "eggshell" calcification. Five case histories are described of workers who were exposed to silica and presented initially with bilateral hilar lymphadenopathy without radiographic evidence of interstitial lung disease. One case progressed to show features of silicosis.
Cardiovascular research 2005 impact factor: New all-time high
Authors: H PIPER, E MARTINSON, T OPTHOF
Journal: Cardiovascular Research (2006)

We are pleased to report to our readers, reviewers, and authors that our impact factor (IF) for the year 2005 has jumped to an all-time high value of 5.283. This is roughly what we had predicted last year [1], after observing a dip in the IF for 2004 that could be readily attributed to the transition in editorship at the beginning of 2003. As the year progresses, we continuously estimate the forthcoming IF with a reliable accuracy (see Fig. 1). These estimates already indicate …
Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia
Authors: Andrew M. Brunner, Hossein Sadrzadeh, Yang Feng, Benjamin J. Drapkin, Karen K. Ballen, Eyal C. Attar, Philip C. Amrein, Steven L. McAfee, Yi‐Bin Chen, Donna S. Neuberg, Amir T. Fathi
Journal: American Journal of Hematology (2013)

Acute myeloid leukemia (AML) is more common and more lethal among patients over the age of 60. Increased body mass index (BMI) has been associated with a higher incidence of various malignancies, including AML. We sought to determine whether patient BMI at the time of AML diagnosis is related to overall survival (OS) among elderly patients. We identified 97 patients with AML diagnosed after the age of 60 and treated with cytarabine‐based induction chemotherapy. The median age was 68 years (range 60–87); 52% of patients were male, and our study population was predominantly white (89% of patients). The median OS for all patients was 316 days (95% CI 246–459). The hazard ratio for mortality was increased among patients with a BMI &lt; 25 compared to BMI ≥ 30 (HR 2.14, P = 0.009, 95% CI 1.21–3.77), as well as with older age (HR 1.76, P = 0.015, 95% CI 1.12–2.79) and with secondary versus de novo disease (HR 1.95, P = 0.006, 95% CI 1.21–3.14). After multivariable analysis, we did not find a significant association between OS and other potential confounders such as coronary artery disease or diabetes among these patients. We conclude that increased BMI was independently associated with improved OS among older AML patients at our institution. Am. J. Hematol. 88:642–646, 2013. © 2013 Wiley Periodicals, Inc.
TCTAP A-075 Prognostic Significance of Anemia in Patients Undergoing PCI with First and Second Generation DES (Katowice Registry)
Authors: Wojciech Wojakowski, Wojciech Wanha, Aleksandra Pluta, Kamil Marcinkiewicz, Jan Dola, Damian Kawecki, Beata Morawiac, Lukasz Krzych, Andrzej Ochala, Michal Tendera
Journal: Journal of the American College of Cardiology (2014)
Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: Further evidence for a unique form of Metabolic Syndrome in HIV patients
Authors: Catherine N. Vu, Raul Ruiz-Esponda, Eric Yang, Evelyn Chang, Baiba Gillard, Henry J. Pownall, Ron C. Hoogeveen, Ivonne Coraza, Ashok Balasubramanyam
Journal: Metabolism (2013)
Erythropoietin receptors in polycythemia vera.
Authors: R T Means, S B Krantz, S T Sawyer, H S Gilbert
Journal: Journal of Clinical Investigation (1989)

The role of erythropoietin (EP) in polycythemia vera (PV) is controversial, with some experiments suggesting that erythroid progenitors in PV are exquisitely sensitive to EP and EP dependent, and others suggesting that PV progenitors are EP independent. We have examined the characteristics of the EP receptor (EP-R) on erythroid colony-forming cells (ECFC) from patients with PV. In contrast to normal ECFC, which have two classes of EP-R, with 20% showing high affinity (Kd = 0.13 nM; range, 0.04-0.20 nM) and the remainder lower affinity (Kd = 0.37 nM; range, 0.28-0.57 nM), PV ECFC show a single class of 851 low affinity EP-R with Kd = 0.72 nM (range, 0.36-0.85 nM). ECFC from patients with secondary (EP driven) polycythemia or anemia show two classes of EP-R (Kd = 0.18 and 1.10 nM, respectively). Attempts to remove tightly bound EP from putative high affinity EP-R in PV did not reveal any higher affinity receptors. Determination of molecular size by crosslinking showed two proteins of 90 and 100 kD similar to those seen with normal EP-R. These studies indicate the PV ECFC have EP-R that are structurally similar to normal EP-R but lack the higher binding affinity for EP.
Different interactions of indomethacin and sulindac with thiazides in hypertension.
Authors: E Steiness, S Waldorff
Journal: BMJ (1982)

Effect of posture and drink volume on the swallowing of capsules Drug-induced oesophageal ulceration is an increasingly recognised problem.1 2 Since ulceration is due to a direct irritant effect the passage of the drug must first be delayed.Tablets have been found3 to stick in the oesophagus.This study shows the effect of posture and drink volume on the oesophageal transit of capsules. Patients, methods, and resultsAfter barium meal and swallow examinations in which normal oesophageal motility was found 50 patients (22 men, 28 women, aged 20-87 years) swallowed four standard hard gelatin capsules (Farillon Lok-Cap) filled with 97% barium sulphate while standing and lying supine with 15 ml and 60 ml water.The time for the capsule to pass from the oropharynx to stomach was measured during screening.If after 10 minutes the capsule remained in the oesophagus, it was washed out with water before proceeding to the next swallow.Four patterns of capsule movement were seen.Normal transit-In 28% of patients all capsules passed into the stomach in < 15 seconds.Delayed transit-In 20% of patients the capsule passed into the stomach in >20 seconds without dispersal.Delay occurred at the level of the left main bronchus on one occasion, above the lower oesophageal sphincter on six, and at both sites on eight.All these patients had gastro-oesophageal