tbuckley/cabot-search huggingface dataset:
Beta adrenergic receptor blockade of feline myocardium. Cardiac mechanics, energetics, and beta adrenoceptor regulation.
Authors: G Cooper, R L Kent, P McGonigle, A M Watanabe
Journal: Journal of Clinical Investigation (1986)

Myocardial oxygen consumption is regulated by interrelated mechanical and inotropic conditions; there is a parallel increase in the aerobic metabolism and inotropic state during beta-adrenergic stimulation under fixed mechanical conditions. In contrast, there is some evidence that beta-blockade may reduce oxygen consumption through effects independent of its influence on mechanical conditions and contractile state, and that prolonged beta-blockade may sensitize the myocardium to beta-adrenergic stimulation. To clarify these two points, the present study examined the relationship of myocardial energetics to mechanics and inotropism during acute beta-blockade and after the withdrawal of long-term beta-blockade, whereupon the basis for any effect observed was sought by characterizing the number, affinity, and affinity states of the beta-receptors as well as the coupling of activated beta-receptors to cyclic AMP generation. Studies of right ventricular papillary muscles from control and chronically beta-blocked cats demonstrated contractile and energetic properties as well as dose-response behavior and inotropic specificity suggestive of an increase in myocardial sensitivity to beta-adrenoceptor stimulation in the latter group. Assays of cardiac beta-adrenoceptors from further groups of control and pretreated cats, both in cardiac tissue and in isolated cardiac muscle cells, failed to define a difference between the two groups either in terms of receptor number and affinity or in terms of the proportion of receptors in the high-affinity state. However, coupling of the activated beta-adrenoceptors to cyclic AMP generation was enhanced in cardiac muscle cells from chronically beta-blocked cats. These data demonstrate that beta-adrenoceptor blockade (a) produces parallel effects on inotropic state and oxygen consumption without an independent effect on either and (b) increases myocardial sensitivity to beta-adrenergic stimulation after beta-blockade withdrawal, not by "up-regulation" of the cardiac beta-adrenoceptors, but instead by more effective coupling of these receptors when activated to cyclic AMP generation.
Abstract 655: Combination of MM-111, an ErbB2/ErbB3 bispecific antibody, with endocrine therapies as an effective strategy for treatment of ER+/HER2+ breast cancer
Authors: Bo Zhang, Alexandra Huhalov, Olga Burenkova, Sharlene Adams, Stephanie Nguyen, Ryan Overland, Arthur J. Kudla, Ulrik B. Nielsen, Clet Niyikiza, Charlotte F. McDonagh, Gavin MacBeath
Journal: Cancer Research (2011)

Abstract Approximately 75% of breast cancers are estrogen receptor (ER) positive. Although endocrine therapies such as tamoxifen, fulvestrant, and letrozole have demonstrated significant efficacy in treating ER+ breast cancer patients, intrinsic or acquired resistance has limited their success. Recent studies suggest that crosstalk between ErbB receptor signaling and ER signaling may contribute to resistance to endocrine therapy. Overexpression of human epidermal growth factor receptor 2 (HER2, synonymous with ErbB2) and upregulation of the ErbB3 ligand heregulin are associated with poor prognosis and reduced overall survival. MM-111 is a novel bispecific antibody fusion protein that specifically targets the ErbB2/ErbB3 heterodimer and blocks heregulin binding to ErbB3. MM-111 inhibits ligand-induced ErbB3 phosphorylation, tumor cell cycle progression, and tumor growth when ErbB2 is overexpressed. We hypothesized that combination of endocrine therapies with MM-111 may improve anti-tumor efficacy. In an estrogen-stimulated BT474-M3 ER-positive breast cancer cell three-dimensional spheroid assay, MM-111, when used as a single agent, showed growth inhibitory effects similar to the anti-estrogen drugs tamoxifen and fulvestrant. Combination of MM-111 with anti-estrogen therapy showed superior activity to either drug alone. In the presence of heregulin, MM-111 maintained its growth inhibitory activity, whereas the inhibitory effect of tamoxifen and fulvestrant was diminished. This suggests that activation of ErbB3 confers tumor cell resistance to anti-estrogen therapies. When both estrogen and heregulin were present, the combination of MM-111 and the anti-estrogen drugs demonstrated a significantly greater inhibitory effect than either drug alone. Western blot analysis showed that treatment of BT-474-M3 cells with the combination of MM-111 and the anti-estrogen drugs significantly increased apoptosis markers such as cytochrome C and BAX. Furthermore, an in vivo BT474-M3 xenograft model showed resistance to tamoxifen treatment (5 mg/pellet, 60-day release). In this xenograft model MM-111 sensitized tumor response to tamoxifen and the combination treatment dramatically inhibited tumor growth. In conclusion, the combination of MM-111 and endocrine therapies may provide a potent regimen that overcomes acquired resistance to endocrine therapies in ER+, ErbB2-overexpressing breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 655. doi:10.1158/1538-7445.AM2011-655
Home visits improve asthma control in low income adults, study shows
Authors: S. Mayor
Journal: BMJ (2014)

Home visits by community health workers significantly improve asthma control and quality of life in low income adults with uncontrolled asthma, show the results of a US study on the benefits of greater support for self management.

Home based support to improve the control of asthma in children is well established, but it has not previously been tested carefully in adults. Researchers randomised 366 adults aged 18 to 65 with uncontrolled asthma, either to receive …
THE TEACHING OF MATERIA MEDICA IN MEDICAL SCHOOLS.
Authors: TORALD SOLLMANN
Journal: JAMA (1904)

<h3>DESIRABILITY OF RESTRICTING THE COURSE OF MATERIA MEDICA.</h3> "I must confess, if I had my way I should abolish materia medica<sup>1</sup>altogether. . . . Not one trace of a knowledge of drugs has remained in my memory from that time to this; and really, as a matter of common sense, I can not understand the arguments for obliging a medical man to know all about drugs, and where they come from. Why not make him belong to the Iron and Steel Institute, and learn something about cutlery, because he uses knives?" . . . "I entertain a very strong conviction that any one who adds to medical education one iota or tittle beyond what is absolutely necessary is guilty of a very grave offense."—Huxley, "On Medical Education," 1870. Everyone will agree with this last sentence. In most medical schools the required class attendance exceeds thirty hours per week,
The antimicrobial peptide <scp>LL</scp>‐37 induces synthesis and release of cysteinyl leukotrienes from human eosinophils – implications for asthma
Authors: J. Sun, B. Dahlén, B. Agerberth, J. Z. Haeggström
Journal: Allergy (2013)

Eosinophils and their products, including leukotrienes and eosinophil cationic protein (ECP), are well-known mediators of inflammation and tissue damage in asthma. The antimicrobial peptide LL-37 exhibits a variety of immunomodulatory activities. However, the role of LL-37 in asthma has not been fully addressed. Here, we aim to investigate the effect of LL-37 on inducing inflammatory mediators in human eosinophils, probe the underlying mechanisms, and search for a clinical correlate.Primary eosinophils were isolated from peripheral blood. Leukotriene and ECP levels were measured using EIAs or ELISAs. Activation of leukotriene-synthesizing enzymes and signaling kinases was analyzed by Western blot or immunofluorescent imaging. LL-37/its proform hCAP18 expression was analyzed by Western blot.LL-37, via formyl peptide receptor-2 (FPR-2), triggered the release of cysteinyl leukotrienes (cys-LTs) from eosinophils. The release was more prominent in cells primed with the eosinophilopoietic cytokine GM-CSF or IL-5 or cells from asthmatic patients. LL-37 stimulates lipid body formation and activates cys-LT-synthesizing enzymes by multiple mechanisms: enhancing cPLA(2) activity by pERK1/2-mediated phosphorylation and inducing intracellular translocation and assembly of 5-LO and LTC(4) S at perinuclear locations and lipid bodies. In addition to cys-LTs, LL-37 enhances ECP release from eosinophils via pERK1/2. The expression of hCAP18 and its release following leukotriene stimulation are significantly higher in eosinophils from asthmatics.This study identifies LL-37 as an eosinophil-activating peptide that triggers release of inflammatory mediators. The clinical correlation suggests that LL-37/hCAP18 and its signaling pathway represent potential therapeutic targets for this disease.
Genetic analysis of the human tumor necrosis factor alpha/cachectin promoter region in a macrophage cell line.
Authors: J S Economou, K Rhoades, R Essner, W H McBride, J C Gasson, D L Morton
Journal: The Journal of Experimental Medicine (1989)

The 615-bp 5' flanking region of the human TNF-alpha/cachectin gene was isolated and ligated to the luciferase reporter gene. In addition, a series of truncated promoter constructs was generated by exonuclease III digestion. The promoter activity of these constructs was studied in a transient transfection system using the TNF-alpha-producing U937 cell line. Full-length and truncated TNF promoter constructions extending from -615 to -95 bp relative to the transcription start site (TSS) could be induced by phorbol esters. A construct truncated to within 36 bp of the TSS (and within 11 bp of the TATAA box) was inactive. Therefore, the phorbol ester responsive is localized in the TNF/cachectin promoter to a relatively short region proximal to the TATAA box.
Practice Gaps in Patient Safety Among Dermatology Residents and Their Teachers
Authors: Jillian Havey Swary, Erik J. Stratman
Journal: JAMA Dermatology (2014)

<h3>Importance</h3> Curriculum and role modeling adjustments are necessary to address patient safety gaps occurring during dermatology residency. <h3>Objective</h3> To identify the source of clinical practices among dermatology residents that affect patient safety and determine the best approach for overcoming gaps in knowledge and practice patterns that contribute to these practices. <h3>Design, Setting, and Participants</h3> A survey-based study, performed at a national medical dermatology meeting in Itasca, Illinois, in 2012, included 142 dermatology residents from 44 residency programs in the United States and Canada. <h3>Main Outcomes and Measures</h3> Self-reported rates of dermatology residents committing errors, identifying local systems errors, and identifying poor patient safety role modeling. <h3>Results</h3> Of surveyed dermatology residents, 45.2% have failed to report needle-stick injuries incurred during procedures, 82.8% reported cutting and pasting a previous author's patient history information into a medical record without confirming its validity, 96.7% reported right-left body part mislabeling during examination or biopsy, and 29.4% reported not incorporating clinical photographs of lesions sampled for biopsy in the medical record at their institution. Residents variably perform a purposeful pause ("time-out") when indicated to confirm patient, procedure, and site before biopsy, with 20.0% always doing so. In addition, 59.7% of residents work with at least 1 attending physician who intimidates the residents, reducing the likelihood of reporting safety issues they witness. Finally, 78.3% have witnessed attending physicians purposefully disregarding required safety steps. <h3>Conclusions and Relevance</h3> Our data reinforce the need for modified curricula, systems, and teacher development to reduce injuries, improve communication with patients and between physicians, residents, and other members of the health care team, and create an environment free of intimidation.
Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity.
Authors: R F Laan, W C Buijs, A L Verbeek, M P Draad, F H Corstens, L B van de Putte, P L van Riel
Journal: Annals of the Rheumatic Diseases (1993)

BACKGROUND. Generalised osteoporosis is often described in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate disease related determinants of bone mineral density (BMD) in patients with RA. METHODS. Subjects were selected from a group of 147 patients with recent onset RA. Disease activity and functional capacity were studied prospectively in this cohort. Activity of the disease was assessed once every three months by various parameters, and functional capacity was measured with a health assessment questionnaire once every six months. Ninety seven patients consented to participate in the study. Bone mineral density was assessed with dual energy x ray absorptiometry in the lumbar spine, in a combined region of interest in the hips, and in Ward9s triangle. Multiple linear regression procedures were used to analyse the data. RESULTS. Duration of RA was negatively associated with BMD at all three sites of measurement. The mean erythrocyte sedimentation rate in the six months before BMD measurement was negatively associated with BMD in the hip and in Ward9s triangle. Other parameters of disease activity were not related to BMD. The mean health assessment questionnaire score in the 18 months before BMD measurement was negatively associated with BMD in the combined hip region only. Bone mineral density tended to be decreased when patients were compared with a normal reference group, especially in the femoral regions of interest. CONCLUSIONS. It is concluded that BMD may be affected in patients with recent onset RA by disease dependent mechanisms. Several factors have been suggested elsewhere as determinants of BMD in RA. The results of this study show that disease duration, disease activity, and functional impairment may, independently of each other, contribute to bone loss, especially in the proximal femur.
Synovial Sarcoma
Authors: Irving M. Ariel, George T. Pack
Journal: New England Journal of Medicine (1963)

THIS is a review of 25 patients bearing synovial sarcomas treated during the past ten years. These sarcomas are relatively rare, comprising approximately 8 per cent of all malignant neoplasms of the soft somatic tissues.1 2 3 4 5 Clinical FeaturesAge and SexThere were 11 males (average age, thirty-four and nine-tenths years) and 14 females (average age, thirty-five years). Synovial sarcoma affects primarily persons in the younger age groups. Over 60 per cent of our patients were under forty years of age.LocationThe lower extremity was most frequently involved (72 per cent), the distribution being as follows: knee, 5; foot, 3; . . .
A prisoner of conscience in Vietnam
Authors: Duncan Forrest
Journal: BMJ (2005)

Monitoring global health Problems are primarily nationalEditor-Murray et al urge for improved global reporting of health data. 1 They also highlight the difficulty of showing national decision makers that good health data can strongly support decision making.Why is this?A reason may be that data are always subject to interpretation.The article by Murray et al is a case in point.They want to establish "an independent monitoring organisation," arguing that the World Health Organization is not fit to undertake the job because of tension between advocacy, monitoring, and evaluation.But evidence that it is this tension that leads to poor monitoring by WHO is weak, at best.In reality, the problems of global health reporting are primarily national (and subnational).The fact that the sum of deaths claimed by different programmes is greater than the actual number of deaths reflects epidemiological methods and the current limitations in global health reporting, more than any WHO failure.The global burden of disease project was limited by these issues, but it was undertaken as effectively in WHO as in any other organisation.Not only are there problems in capacity, understanding the value of surveillance, and coverage of health services.The reporting of health events can be politically sensitive or even economically damaging.It is therefore likely that political interference will continue (whoever collects the data) until governments can be shown that honesty pays.It is perhaps this failure that needs to be dealt with rather than setting up yet another organisation without a proper analysis of the reasons (and locus) for failures in global health reporting.
First confirmed case of Crimean-Congo haemorrhagic fever in the UK
Authors: David A Barr, Celia Aitken, David J Bell, Colin S Brown, Ian Cropley, Naghum Dawood, Susan Hopkins, Michael Jacobs, Benjamin Jeffs, Alisdair MacConnachie, David W Mulvaney, Edward Nicol, Raymond Fox
Journal: The Lancet (2013)
Wellcome Trust and drug giants fund gene marker database
Authors: R. Woodman
Journal: BMJ (1999)

A two year, £28m ($44.8m) initiative to create a high quality map of genetic markers, which will be available to everyone without charge, has been launched by the Wellcome Trust together with a group of leading pharmaceutical companies and academic centres.

The collaborative effort, called the SNP Consortium, will seek to identify and analyse single nucleotide polymorphisms involved in disease processes so that safer and more effective drugs can be developed.

Single nucleotide polymorphisms, sometimes called “snips,” are common variations that occur …
KNIFE CURETTE. ESPECIALLY ADAPTED FOR OPERATIONS ON THE BONES AND CARTILAGES.
Authors: A. H. MEISENBACH
Journal: JAMA (1893)

This instrument is fashioned somewhat after the farrier's knife. It consists of a blade (<i>a</i>) placed in a seperable handle (<i>b</i>) as shown in the upper figure of the cut. The cutting part of the blade is placed at an obtuse angle to the shaft: This gives a greater degree of leverage. The end of the blade is bent upon itself so as to form a loop or part of a circle. By means of this construction, the instrument has a round as well as a linear cutting edge. The handle is made of metal in two seperabel parts, with a simple but effective lock and catch, as is seen in the lower figure of the cut. There are four blades of various sizes. The figures are of one third actual size, with the exception of outline figures, (<i>c</i>) of the loops of cutting blade, which are actual size. The
A proto-oncogene BCL6 is up-regulated in the bone marrow microenvironment in multiple myeloma cells
Authors: Teru Hideshima, Constantine Mitsiades, Hiroshi Ikeda, Dharminder Chauhan, Noopur Raje, Gullu Gorgun, Hiromasa Hideshima, Nikhil C. Munshi, Paul G. Richardson, Daniel R. Carrasco, Kenneth C. Anderson
Journal: Blood (2010)
A role for PKC in foam cell formation?
Authors: K. Szilagyi, T. K. van den Berg
Journal: Cardiovascular Research (2012)

With great interest we have read the recently published article by Lin et al . 1 where PKCδ is described to regulate uptake of oxLDL and the resultant foam cell formation, thereby suggesting a potential role of this protein kinase in atherogenesis. In their study Lin et al . used two cell types, THP-1 monocytic cell line and primary human macrophages, as models for oxLDL uptake and in vitro foam cell formation. Employing RNA interference they decreased expression of PKCδ by an …
Effects of histamine on lung permeability in normal and asthmatic subjects.
Authors: P J Rees, D Shelton, T B Chan, N Eiser, T J Clark, M N Maisey
Journal: Thorax (1985)

The permeability of respiratory mucosa, as measured by clearance of diethylenetriamine penta-acetate (DTPA) labelled with technetium 99m, was similar in seven normal and nine asthmatic subjects. Histamine induced bronchoconstriction was associated with a 50% increase in permeability in both groups of subjects. In normal subjects inhaled salbutamol, given as 1 mg acutely or as 200 micrograms four times daily for two weeks, had no effect on pulmonary permeability. Salbutamol, given before histamine challenge, prevented bronchoconstriction, but did not affect the increase in permeability seen in normal subjects. Low doses of histamine, sufficient to cause bronchoconstriction in the asthmatic subjects, produced little bronchoconstriction in normal subjects but caused increases in lung permeability similar to those seen in asthmatic subjects. These studies suggest that these two effects of inhaled histamine, bronchoconstriction and increased permeability, are independent.
Assessing the effect of the 2001–06 Mexican health reform: an interim report card
Authors: Emmanuela Gakidou, Rafael Lozano, Eduardo González-Pier, Jesse Abbott-Klafter, Jeremy T Barofsky, Chloe Bryson-Cahn, Dennis M Feehan, Diana K Lee, Hector Hernández-Llamas, Christopher JL Murray
Journal: The Lancet (2006)
PREDICTION OF CARDIOVASCULAR EVENTS WITH AORTIC STIFFNESS IN PATIENTS WITH ERECTILE DYSFUNCTION
Authors: Charalambos Vlachopoulos, Nikolaos Ioakeimidis, Konstantinos Aznaouridis, Dimitrios Terentes-Printzios, Konstantinos Rokkas, Athanasios Aggelis, Alexandros Synodinos, Euaggelia Christoforatou, Dimosthenis Panagiotakos, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2012)
Provocation of an Autoimmune Response to Cardiac Voltage-Gated Sodium Channel NaV1.5 Induces Cardiac Conduction Defects in Rats
Authors: Sevil Korkmaz, Edgar Zitron, Anna Bangert, Claudia Seyler, Shiliang Li, Peter Hegedüs, Daniel Scherer, Jin Li, Thomas Fink, Patrick A. Schweizer, Evangelos Giannitsis, Matthias Karck, Gábor Szabó, Hugo A. Katus, Ziya Kaya
Journal: Journal of the American College of Cardiology (2013)
Determinants of systemic vascular resistance in children with congenital heart disease
Authors: G. W MORRISON, F. J MACARTNEY
Journal: Cardiovascular Research (1981)

It is well known on the basis of acute experiments that changes in systemic arterial oxygen saturation, haemoglobin concentration and acid-base state produce changes in systemic vascular resistance. However, it is not known whether the same changes occur in the chronic state. In order to investigate this problem, we measured systemic vascular resistance in a population in whom chronic changes in these variables are common, namely 195 subjects with congenital heart disease. The significance of these factors was assessed by their ability to predict systemic vascular resistance in a multiple regression equation which also took account of the size of the patient. No matter how the size of the patient was allowed for, haemoglobin concentration, systemic arterial pH (or non-respiratory pH) and systemic arterial oxygen saturation were significantly (P < 0.025) and positively correlated with systemic vascular resistance. We conclude that, as far as these factors are concerned, the mechanisms operating in the acute state continue to function in the chronic state.