tbuckley/cabot-search huggingface dataset:
STUDIES OF PPLO INFECTION
Authors: Lewis Thomas, Morton Davidson, Robert T. McCluskey
Journal: The Journal of Experimental Medicine (1966)

Turkey poults injected intravenously with suspensions of Mycoplasma gallisepticum develop a fatal neurologic disease associated with polyarteritis affecting almost exclusively the cerebral arteries. The incubation period depends on the dose of organisms. With high doses (1010 to 1011 mycoplasmas) the birds become ill and die within a few hours; with lower doses (106 to 108) neurologic manifestations appear after 7 days. The rapid onset of neurologic signs after high doses indicates the presence of a toxin in the mycoplasma, but efforts to extract toxin from disrupted organisms or to demonstrate its presence in culture fluid free of mycoplasmas have been unsuccessful. The toxin appears to be associated only with living mycoplasmas. The toxic component of M. gallisepticum is inactivated by heating the organisms at 50°C, disruption by repeated cycles of freezing and thawing, and exposure to specific antibody. Treatment of turkeys with gold thiomalate furnishes partial protection against the toxic effects of large doses of mycoplasmas, and protection against the development of cerebral arteritis. Treatment with tetracycline protects completely against both toxicity and arteritis, and, when delayed, restores diseased birds to a healthy state. Cortisone, methotrexate and 6-mercaptopurine have no effect on the course or outcome of the disease. Intracerebral injections of M. gallisepticum are less toxic and lethal than when the same dose was given by vein, indicating that the organism exerts its damaging action on blood vessels by way of the blood stream. The arterial lesions resemble those of serum sickness, except for their distribution, and are associated with glomerular inflammatory lesions. However, for various reasons discussed, it is considered more likely that they result from a direct toxic action of living mycoplasmas on the vessels concerned than from an immunologic mechanism.
Mechanical Unloading During Left Ventricular Assist Device Support Increases Left Ventricular Collagen Cross-Linking and Myocardial Stiffness
Authors: Stefan Klotz, Robert F. Foronjy, Marc L. Dickstein, Anguo Gu, Ingrid M. Garrelds, A.H. Jan Danser, Mehmet C. Oz, Jeanine D’Armiento, Daniel Burkhoff
Journal: Circulation (2005)

Background— Left ventricular assist devices (LVADs) induce reverse remodeling of the failing heart except for the extracellular matrix, which exhibits additional pathophysiological changes, although their mechanisms and functional consequences are unknown. Methods and Results— Hearts were obtained at transplant from patients with idiopathic dilated cardiomyopathy (DCM) not requiring LVAD support (n=30), patients requiring LVAD support (n=16; LVAD duration, 145±33 days), and 5 nonfailing hearts. Left (LV) and right ventricular (RV) ex vivo pressure-volume relationships were measured, and chamber and myocardial stiffness constants were determined. Myocardial tissue content of total and cross-linked collagen, collagen types I and III, MMP-1, MMP-9, TIMP-1, and angiotensin (Ang) I and II were measured. LV size, mass, and myocyte diameter decreased after LVAD compared with DCM without LVAD ( P &lt;0.05). Total and cross-linked collagen and ratio of type I to III collagen increased in DCM compared with nonfailing hearts and increased further after LVAD ( P &lt;0.05 versus DCM and nonfailing). Concomitantly, chamber and myocardial stiffness increased with LVAD. The ratio of MMP-1 to TIMP-1 increased in DCM and almost normalized after LVAD, favoring decreased collagen degradation. Tissue Ang I and II also increased during LVAD. There was no significant change in the RV of LVAD-supported heart compared with DCM. Conclusions— LVAD support increases LV collagen cross-linking and the ratio of collagen type I to III, which is associated with increased myocardial stiffness. Decreased tissue MMP-1–to–TIMP-1 ratio (decreased degradation) and increased Ang levels (stimulants of synthesis) are likely mechanisms for these changes. Lack of significant effects on the RV suggest that hemodynamic unloading of the LV (not provided to the RV) might be the primary factor that regulates these extracellular matrix changes.
Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index
Authors: R. Suppiah, O. Flossman, C. Mukhtyar, F. Alberici, B. Baslund, D. Brown, N. Hasan, J. Holle, Z. Hruskova, D. Jayne, A. Judge, M. A. Little, P. A. Merkel, A. Palmisano, P. Seo, C. Stegeman, V. Tesar, A. Vaglio, K. Westman, R. Luqmani
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Abstract</h3> An increasing challenge in population health research is efficiently utilising the wealth of data available from multiple sources to investigate the mechanisms of disease and identify potential intervention targets. The use of biomedical data integration platforms can facilitate evidence triangulation from these different sources, improving confidence in causal relationships of interest. In this work, we aimed to integrate Mendelian randomization (MR) and literature-mined evidence from the EpiGraphDB knowledge graph to build a comprehensive overview of risk factors for developing breast cancer. We utilised MR-EvE ("Everything-vs-Everything") data to generate a list of causal risk factors for breast cancer, integrated this data with literature-mined relationships and identified potential mediators. We used multivariable MR to evaluate mediation and estimate the direct effects of these traits. We identified 213 novel and established lifestyle and molecular traits with evidence of an effect on breast cancer. We present the results of this evidence integration for four case studies (insulin-like growth factor I, cardiotrophin-1, childhood body size and age at menopause). We demonstrate that using MR-EvE to identify disease risk factors is an efficient hypothesis-generating approach. Moreover, we show that integrating MR evidence with literature-mined data may identify causal intermediates and uncover the mechanisms behind disease.
Efficacy of personal symptom and family history questionnaires when screening for inherited cardiac pathologies: the role of electrocardiography
Authors: M G Wilson, S Basavarajaiah, G P Whyte, S Cox, M Loosemore, S Sharma
Journal: British Journal of Sports Medicine (2007)

This study sought to confirm the efficacy of using resting 12-lead ECG alongside personal symptom and family history questionnaires and physical examination when screening for diseases with the potential to cause sudden cardiac death in the young.1074 national and international junior athletes (mean age 15.8 (SD 0.7) years, range 10 to 27) and 1646 physically active schoolchildren (16.1 (SD 2.1) years, range 14 to 20) were screened using personal and family history questionnaires, physical examination and resting 12-lead ECG. Nine participants with a positive diagnosis of a disease associated with sudden cardiac death were identified. None of the participants diagnosed with a disease associated with sudden cardiac death were symptomatic or had a family history of note.Family history and personal symptom questionnaires alone are inadequate to identify people with diseases associated with sudden cardiac death. Use of the 12-lead ECG is essential when screening for cardiac pathology in the young.
Prolonged Caloric Restriction in Obese Patients With Type 2 Diabetes Mellitus Decreases Plasma CETP and Increases Apolipoprotein AI Levels Without Improving the Cholesterol Efflux Properties of HDL
Authors: Yanan Wang, Marieke Snel, Jacqueline T. Jonker, Sebastiaan Hammer, Hildo J. Lamb, Albert de Roos, A. Edo Meinders, Hanno Pijl, Johannes A. Romijn, Johannes W.A. Smit, Ingrid M. Jazet, Patrick C.N. Rensen
Journal: Diabetes Care (2011)

Using a mouse model for human-like lipoprotein metabolism, we observed previously that reduction of the hepatic triglyceride (TG) content resulted in a decrease in plasma cholesteryl ester transfer protein (CETP) and an increase in HDL levels. The aim of the current study was to investigate the effects of prolonged caloric restriction in obese patients with type 2 diabetes mellitus, resulting in a major reduction in hepatic TG content, on plasma CETP and HDL levels.We studied 27 obese (BMI: 37.2 ± 0.9 kg/m(2)) insulin-dependent patients with type 2 diabetes mellitus (14 men and 13 women, aged 55 ± 2 years) who received a 16-week very low calorie diet (VLCD). At baseline and after a 16-week VLCD, plasma lipids, lipoproteins, and CETP were measured. Furthermore, functionality of HDL with respect to inducing cholesterol efflux from human monocyte cells (THP-1) was determined.A 16-week VLCD markedly decreased plasma CETP concentration (-18%; P < 0.01) and increased plasma apolipoprotein (apo)AI levels (+16%; P < 0.05), without significantly affecting plasma HDL-cholesterol and HDL-phospholipids. Although a VLCD results in HDL that is less lipidated, the functionality of HDL with respect to inducing cholesterol efflux in vitro was unchanged.The marked decrease in hepatic TG content induced by a 16-week VLCD is accompanied by a decrease in plasma CETP concentration and an increase in apoAI levels, without improving the cholesterol efflux properties of HDL in vitro.
Optical Imaging of Voltage and Calcium in Cardiac Cells &amp; Tissues
Authors: Todd J. Herron, Peter Lee, José Jalife
Journal: Circulation Research (2012)

Cardiac optical mapping has proven to be a powerful technology for studying cardiovascular function and disease. The development and scientific impact of this methodology are well-documented. Because of its relevance in cardiac research, this imaging technology advances at a rapid pace. Here, we review technological and scientific developments during the past several years and look toward the future. First, we explore key components of a modern optical mapping set-up, focusing on: (1) new camera technologies; (2) powerful light-emitting-diodes (from ultraviolet to red) for illumination; (3) improved optical filter technology; (4) new synthetic and optogenetic fluorescent probes; (5) optical mapping with motion and contraction; (6) new multiparametric optical mapping techniques; and (7) photon scattering effects in thick tissue preparations. We then look at recent optical mapping studies in single cells, cardiomyocyte monolayers, atria, and whole hearts. Finally, we briefly look into the possible future roles of optical mapping in the development of regenerative cardiac research, cardiac cell therapies, and molecular genetic advances.
Artemisinin Resistance in<i>Plasmodium falciparum</i>Malaria
Authors: Arjen M. Dondorp, François Nosten, Poravuth Yi, Debashish Das, Aung Phae Phyo, Joel Tarning, Khin Maung Lwin, Frederic Ariey, Warunee Hanpithakpong, Sue J. Lee, Pascal Ringwald, Kamolrat Silamut, Mallika Imwong, Kesinee Chotivanich, Pharath Lim, Trent Herdman, Sen Sam An, Shunmay Yeung, Pratap Singhasivanon, Nicholas P.J. Day, Niklas Lindegardh, Duong Socheat, Nicholas J. White
Journal: New England Journal of Medicine (2009)

Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance.In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance.We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate-mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P=0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups.P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.)
Letter by Lozano et al Regarding Articles, “Transcatheter Valve-in-Valve Implantation for Failed Bioprosthetic Heart Valves” and “Percutaneous Therapy for Valvular Heart Disease: A Huge Advance and a Huge Challenge to Do It Right”
Authors: Iñigo Lozano, David Calvo, Juan Rondan
Journal: Circulation (2011)
Predictors of Antidepressant Prescription and Early Use Among Depressed Outpatients
Authors: J A Sirey, B S Meyers, M L Bruce, G S Alexopoulos, D A Perlick, P Raue
Journal: American Journal of Psychiatry (1999)

The rates of antidepressant recommendation and use were determined in outpatients with major depression receiving services in mental health clinics. Site of service and the patients' sociodemographic and clinical characteristics were investigated as possible predictors.Patients admitted to six outpatient clinics were recruited through a two-stage sampling procedure. Patients with major depressive disorder (N = 124) according to the Structured Clinical Interview for DSM-IV--Patient Edition were assessed at admission and 3 months later.Drug therapy was recommended for most patients (71%), and minimal use (at least 1 week) was recorded for 59% of the subjects. White patients were nearly three times as likely to receive a recommendation for antidepressants. Antidepressant recommendation was also associated with severity of depressed mood, recent medication use, and clinic type. Recent antidepressant use was the only variable that predicted whether the patient actually took the recommended medication.Many patients with depression seeking treatment at community mental health clinics do not receive antidepressant drug therapy. The offer of medication is predicted by patient ethnicity, clinic type, and symptom severity. Minority patients are less likely to be offered antidepressant treatment.
Stress reaction of the humerus in tennis players
Authors: Rogerio Teixeira Silva, Luis Guilherme Hartmann, Cristiano Frota de Souza Laurino
Journal: British Journal of Sports Medicine (2007)

Background: Overuse injuries are a frequent occurrence among competitive athletes. When analysing the incidence of overuse injuries in tennis players, it has been determined that a significant number of these injures occur in the upper limb area. In this study, we describe five cases of a stress-induced injury to the middle and distal humerus occurring mainly due to repetitive serving. Methods: Athletes studied were competitive tennis players and elite junior players, two of whom played at international level. Four of the five were male. In all cases, diagnosis was confirmed by magnetic resonance imaging examination. The treatment of middle and distal humeral stress reactions consisted of physical therapy, which focused on analgesia and muscle strengthening. In addition, we analysed each tennis player’s strokes in order to identify modifications that would decrease the amount of stress that the upper limbs were subjected to during the service motion. Results: The players in our study missed on average 3 weeks of play and at follow-up after 1 year were able to play symptom free. Conclusions: Our study highlights the need for coaches, physicians and players to be aware of distal humeral pain and understand treatment options in order to prevent further injury, including stress fractures.
Secreted enteric antimicrobial activity localises to the mucus surface layer
Authors: U Meyer-Hoffert, M W Hornef, B Henriques-Normark, L-G Axelsson, T Midtvedt, K Putsep, M Andersson
Journal: Gut (2008)

The intestinal mucosa is constantly exposed to a dense and highly dynamic microbial flora and challenged by a variety of enteropathogenic bacteria. Antibacterial protection is provided in part by Paneth cell-derived antibacterial peptides such as the alpha-defensins. The mechanism of peptide-mediated antibacterial control and its functional importance for gut homeostasis has recently been appreciated in patients with Crohn's ileitis. In the present study, the spatial distribution of antimicrobial peptides was analysed within the small intestinal anatomical compartments such as the intestinal crypts, the overlaying mucus and the luminal content.Preparations from the different intestinal locations as well as whole mouse small intestine were extracted and separated by reversed-phase high-performance liquid chromatography. Antibacterial activity was determined in extracts, and the presence of antimicrobial peptides/proteins was confirmed by N-terminal sequencing, mass spectrometry analysis and immunodetection.The secreted antibacterial activity was largely confined to the layer of mucus, whereas only minute amounts of activity were noted in the luminal content. The extractable activity originating from either crypt/mucus/lumen compartments respectively (given as a percentage) was for Listeria monocytogenes, 48 (4)/44 (4)/8 (8); Enterococcus faecalis, 44 (10)/49 (3)/7 (7); Bacterium megaterium, 56 (4)/42 (3)/2 (1); Streptococcus pyogenes, 48 (4)/46 (3)/6 (6); Escherichia coli, 46 (4)/47 (3)/7 (7); and Salmonella enterica sv. Typhimurium, 38 (3)/43 (7)/19 (10). A spectrum of antimicrobial peptides was identified in isolated mucus, which exhibited strong and contact-dependent antibacterial activity against both commensal and pathogenic bacteria.These findings show that secreted antimicrobial peptides are retained by the surface-overlaying mucus and thereby provide a combined physical and antibacterial barrier to prevent bacterial attachment and invasion. This distribution facilitates high local peptide concentration on vulnerable mucosal surfaces, while still allowing the presence of an enteric microbiota.
Integrated analysis of microRNA and mRNA expression and association with HIF binding reveals the complexity of microRNA expression regulation under hypoxia
Authors: Carme Camps, Harpreet K Saini, David R Mole, Hani Choudhry, Martin Reczko, José Guerra-Assunção, Ya-Min Tian, Francesca M Buffa, Adrian L Harris, Artemis G Hatzigeorgiou, Anton J Enright, Jiannis Ragoussis
Journal: Molecular Cancer (2014)

In mammalians, HIF is a master regulator of hypoxia gene expression through direct binding to DNA, while its role in microRNA expression regulation, critical in the hypoxia response, is not elucidated genome wide. Our aim is to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression.
Did the drug do it?
Authors: M J Langman
Journal: BMJ (1986)

Did the drug do it?The refined techniques now used in the development of drugs have increased the precision with which individual pharmacological systems may be stimulated or suppressed while closely similar systems serving different functions are more or less unaffected.These advances are usually described in pharmacological jargon: we are now all familiar with drugs which affect mainly H2 but not H1, M2 but not MI, and 12 but not Pi receptors.Some important but not immediately obvious consequences have come from these developments-and these may both alter and diminish our chances of detecting adverse drug effects.The close control of molecular development and then of pharmacological and toxicological testing may have reduced the chances ofa drug being released for general use which has predictable adverse effects arising from its mode of action.These changes have also reduced the chances of a drug having unpredictable effects which occur with reasonable frequency during short term use.When side effects are both unpredictable and rare their detection has always been a matter of chance; and such reactions seem likely to continue to pose problems.If modern drugs are perceived as powerful but relatively safe they will be widely used, and in these circumstances toxic reactions of low frequency will become increasingly important.The unavoidable reality is that if prescription numbers are in millions but reactions occur once every 10 000 treatments then reactions will occur in hundreds.Paradoxically, however, the individual general practitioner who prescribes may not expect to meet such a reaction even once in 10 years.Once a drug has been released after clinical trials any adverse effects may come to light in various ways.Individual doctors may report their suspicions through the national yellow card scheme and through reporting cases in medical journals or to the pharmaceutical companies responsible for marketing the products.In all these circumstances the association of event with drug implies a causal link, but this may not necessarily be the case.In each case many questions need answering: might, say, the observed jaundice have been due to non-A non-B hepatitis and not the drug?Might another agent have been responsible?Might the event have been a manifestation of an existing disease?Case reports in medical journals may achieve wide publicity which is not always justified, and editors and reviewers as well as aspiring authors need to maintain critical minds.