tbuckley/cabot-search huggingface dataset:
Leukotrienes and Prostaglandins in Asthma
Authors: H. Bisgaard
Journal: Allergy (1984)

Leukotrienes and prostaglandins possess properties which are central in the asthmatic reaction. They are bronchoconstrictors, they inhibit the mucociliary clearance, increase blood flow and permeability and thereby induce edema formation, and they attract and activate leukocytes. They are formed partly by allergic reactions and partly by a large number of other more non-specific reactions. Finally, the concentration of prostanoids has been found increased in the asthmatic reaction in vivo. The leukotrienes have not been traced in vivo in asthmatic attacks so far, but have been found in vivo in man in a specific type I allergic conjunctival reaction. Much evidence suggests that these mediators are relevant in asthmatic diseases, even though prostaglandin inhibitors have no effect in asthma. There still remains the need to investigate the influence on asthmatic diseases by as yet unavailable leukotriene blocking agents. Even though leukotrienes are judged today to be important mediators in asthma, it does not seem reasonable to expect that a single mediator is responsible for asthmatic diseases. Rather, it seems quite likely that asthma is caused by a complex interplay of a large number of mediators, circulating hormones, nervous mechanisms, receptor abnormalities, intracellular metabolic defects, etc. Despite this complexity, investigations in recent years have increased the knowledge of the biochemistry and human physiological effects of leukotrienes and prostaglandins which has created an improved understanding of the asthmatic reaction's pathophysiology, contributed a pharmacological rationale for previously used therapy, and stimulated new perspectives for specific pharmacological research.
Killing of intracellular Leishmania donovani by human mononuclear phagocytes. Evidence for oxygen-dependent and -independent leishmanicidal activity.
Authors: H W Murray, D M Cartelli
Journal: Journal of Clinical Investigation (1983)

Human peripheral blood monocytes were cultivated for 1-30 d before assay for H2O2 release or challenge with Leishmania donovani promastigotes (LDP) or amastigotes (LDA). 1-d cells readily generated H2O2 in response to both phorbol myristate acetate triggering (1,013 +/- 58 nmol/mg protein . 90 min) and LDP ingestion, and killed 50% of LDP within 6 h, and 90% by 24 h. In contrast, the same cells released little H2O2 during LDA ingestion, killed no LDA at 6 h and less than 30% by 24 h, and supported intracellular LDA replication. Monocyte-derived macrophages (cells first cultivated for greater than or equal to 7 d) generated less than 125 nmol H2O2/mg . 90 min after phorbol myristate acetate triggering, killed neither LDP nor LDA, and permitted both forms to replicate. The addition of mitogen- or antigen-stimulated lymphokines, however, prevented the decline in monocyte oxidative capacity, enhanced macrophage H2O2 release by more than sixfold, and, in parallel, induced 1-d monocytes to kill LDA and cultivated macrophages to display both promastigocidal and amastigocidal activity. In comparison to 1-d monocytes and lymphokine-activated macrophages from normal donors, the same cells from patients with chronic granulomatous disease (CGD) or normal cells whose oxidative activity had been impaired by catalase pretreatment or glucose deprivation exerted considerably less or no antileishmanial activity during the early (6-24 h) postphagocytic period. By 48 h after infection, however, 1-d CGD monocytes and oxidatively impaired normal cells killed 40 and greater than 80% of LDP, respectively. Although a longer period of lymphokine stimulation was required and the resulting antileishmanial effects were not as rapid as with normal cells, activated CGD monocytes and macrophages also eventually achieved promastigocidal and amastigostatic activity. These results indicate that human mononuclear phagocytes utilize both oxygen-dependent and -independent mechanisms to achieve activity against ingested Leishmania, and also demonstrate (a) the differential susceptibilities of the two forms of L. donovani to intracellular killing, (b) the key role of oxygen intermediates in effective mononuclear phagocyte antimicrobial activity, (c) the capacity of lymphocyte products to enhance oxygen-dependent as well as -independent pathways, and (d) the vulnerability of the monocyte-derived macrophage to Leishmania infection in the absence of lymphokine stimulation.
Activation of CD4 cells by fibronectin and anti-CD3 antibody. A synergistic effect mediated by the VLA-5 fibronectin receptor complex.
Authors: T Matsuyama, A Yamada, J Kay, K M Yamada, S K Akiyama, S F Schlossman, C Morimoto
Journal: The Journal of Experimental Medicine (1989)

In this study, fibronectin synergized with anti-CD3 antibody to promote CD4 cell proliferation in a serum-free culture system. The cell-adhesive domain plus additional regions of the fibronectin molecule are involved in this synergy. Anti4B4(CDw29) antibody blocked the activation of CD4 cells in this system. Furthermore, it is the VLA-5 protein within the set of molecules recognized by anti-4B4 that serves as a fibronectin receptor on the CD4 lymphocytes. The VLA-5 fibronectin receptor was mainly expressed on CD4+ CD45R-CDw29+ cells and may in part contribute to the unique function of these cells.
Molecular Imaging in Hereditary Succinate Dehydrogenase Mutation–Related Paragangliomas
Authors: Maria Cristina Marzola, Domenico Rubello
Journal: Clinical Nuclear Medicine (2014)

Multiple paraganglioma (PGL) syndromes related to succinate dehydrogenase (SDH) gene mutations are rare hereditary conditions. These present with heterogeneous clinical signs and symptoms and in many cases are difficult to classify. We summarize the pathophysiological, clinical, laboratory, and morphological and functional imaging characteristics of SDH gene mutation PGLs, emphasizing 18F-FDG and 18F-DOPA PET/CT. We correlate clinical and genetic features of SDH-related PGLs with specific PET radiopharmaceuticals, with the aim to obtain an “individualized” diagnostic approach.
Combinatorial Control of Suicide Gene Expression by Tissue-specific Promoter and microRNA Regulation for Cancer Therapy
Authors: Chunxiao Wu, Jiakai Lin, Michelle Hong, Yukti Choudhury, Poonam Balani, Doreen Leung, Lam H Dang, Ying Zhao, Jieming Zeng, Shu Wang
Journal: Molecular Therapy (2009)

Transcriptional targeting using a tissue-specific cellular promoter is proving to be a powerful means for restricting transgene expression in targeted tissues. In the context of cancer suicide gene therapy, this approach may lead to cytotoxic effects in both cancer and nontarget normal cells. Considering microRNA (miRNA) function in post-transcriptional regulation of gene expression, we have developed a viral vector platform combining cellular promoter-based transcriptional targeting with miRNA regulation for a glioma suicide gene therapy in the mouse brain. The therapy employed, in a single baculoviral vector, a glial fibrillary acidic protein (GFAP) gene promoter and the repeated target sequences of three miRNAs that are enriched in astrocytes but downregulated in glioblastoma cells to control the expression of the herpes simplex virus thymidine kinase (HSVtk) gene. This resulted in significantly improved in vivo selectivity over the use of a control vector without miRNA regulation, enabling effective elimination of human glioma xenografts while producing negligible toxic effects on normal astrocytes. Thus, incorporating miRNA regulation into a transcriptional targeting vector adds an extra layer of security to prevent off-target transgene expression and should be useful for the development of gene delivery vectors with high targeting specificity for cancer therapy.
HIV Seroprevalence in Newborns in New York State
Authors: Lloyd F. Novick
Journal: JAMA (1989)

The prevalence of human immunodeficiency virus (HIV) infection was determined in women at the time of childbirth throughout New York State between November 30, 1987, and November 30, 1988. Mandatory blood specimens (276,609) obtained from all newborns were examined for HIV. The overall HIV seroprevalence rate was 0.66% (1816 newborns), with 0.16% in Upstate New York and 1.25% in New York City. Rates for newborns whose mothers were aged 20 to 29 years (1.30%) and 30 to 39 years (1.35%) were significantly higher than rates for those with mothers younger than 20 years of age (0.72%). Rates of seropositivity were higher among blacks (1.8%) and Hispanics (1.3%) than among whites (0.13%). Seropositivity of HIV was higher in zip code areas with high rates of drug use (2.2%) than in the rest of New York City (0.8%). It is estimated that more than 726 HIV-infected children were born in New York State during the 1-year study period, using 40% as the probable proportion of seropositives that will become infected.
Metabolic Syndrome and Risk of Coronary, Cerebral, and Peripheral Vascular Disease in a Large Dutch Population With Familial Hypercholesterolemia
Authors: Jamal S. Rana, Angelique C. Jansen, Aeilko H. Zwinderman, Max Nieuwdorp, Emily S. van Aalst-Cohen, J. Wouter Jukema, Mieke D. Trip, John J.P. Kastelein
Journal: Diabetes Care (2006)

Various studies (1–16) in recent years have reported that the metabolic syndrome is associated with an increase in cardiovascular disease (CVD). However, there is still an uncertainty about the clinical importance and consequences of the metabolic syndrome (17). There is paucity of data looking at the effect of metabolic syndrome, specifically on cerebrovascular (CeVD) (9,12,18,19) and peripheral vascular (PVD) disease. Heterozygous familial hypercholesterolemia (FH) is a common hereditary disorder of lipoprotein metabolism (prevalence 1:400). The disorder is caused by mutations in the LDL receptor gene. The objective of our study was to assess if there was an additional risk associated with the presence of metabolic syndrome for coronary disease, CeVD, and PVD in this high-risk population, which included patients inducted from 27 clinics around the Netherlands.

The database for the current study is the molecular diagnostic center for nationwide FH screening in the Netherlands, located at the Academic Medical Centre, University of Amsterdam. A total of 2,400 patients fulfilled the diagnostic criteria for FH and were included in the study. The inclusion and exclusion criteria for participation in the study and details of the data collection are outlined and previously discussed in detail (20–22). The ethics institutional review board of each participating hospital approved …
Diets For Patients With Chronic Kidney Disease, Still Worth Prescribing
Authors: William E. Mitch, Guiseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2004)

Dietary indiscretion contributes to the severity of many diseases such as inherited metabolic disorders like phenylketonuria in which excess dietary protein causes symptoms. But, dietary indiscretion also causes symptoms in more common diseases. For example, excessive carbohydrate intake will
Pain speaking--and anesthesiologists answer
Authors: M. F. Goldsmith
Journal: JAMA (1992)

IN CONTRAST with the traditional role of the anesthesiologist—putting patients to sleep and waking them up after some perhaps painful disorder has been surgically dealt with—the subspecialty called pain management requires physicians to treat pain as an entity.  We now know that pain is not merely a passive symptom of disease, but an aggressive disease in itself, producing changes in the brain that underlie the pathology of persistent or chronic pain, says Ronald Dubner, DDS, PhD, chief of the Neurobiology and Anesthesiology Branch of the National Institute of Dental Research (part of the National Institutes of Health), Bethesda, Md.  Pain Research   The institute was a cosponsor, along with the National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, National Institute on Drug Abuse, American Pain Society, and International Association for the Study of Pain, of a symposium entitled Frontiers of Pain Research in the Decade of
Cooperating, not competing, to improve health care
Authors: D. Berwick, R. Smith
Journal: BMJ (1995)

Cooperation may become most difficult just when it is most needed. When stress is high, fear develops; and fear fragments us. Health care leaders should now be working more and more closely with each other, seeking systemic solutions for systemic problems, but the opposite is happening. As demands to cut costs increase and as governments and other groups paying for health care probe the system for evidence of safety and effectiveness, professions tend to retreat within their own walls, organisations become increasingly secretive, and individuals struggle against their interdependencies.

We have seen this in the United States as reform of health care has gained momentum, mostly induced by large corporate purchasers of care, which provide most of the health care insurance for the American population. These purchasers have been angered by the steady growth in American health care costs—almost three times the rate of inflation for over two decades—without strong evidence either of added benefit to the population or of effective efforts by health care organisations to control their own costs. Trust has been broken, and those paying for health care are now more assertive than ever before. They are requiring organisations to provide data on their performance, including data not only on costs but also on health status outcomes, rates of use of diagnostic and therapeutic procedures, and patients' satisfaction. Standardised scoring systems—so called “report cards”—are appearing more and more frequently, and the demise of the federal government's efforts to enact health reform has not slowed these moves by the private sector towards accountability and measurement of performance.

American health …
The Broken Image: Man, Science and Society
Authors: Martin Hoffman
Journal: JAMA (1964)

The argument of this book is that social science is dominated by "root metaphors and routine methods appropriated from classical mechanics," and that this keeps us from seeing "the whole man"; we see only a broken self-image. The author has certainly identified and attacked a number of outworn, indefensible doctrines: materialist metaphysics, naive behaviorism, the apotheosis of mathematical and statistical methods in social science, the claim that science can be altogether value-free, the bureaucratization of administration, the denial of the limits of scientific method, the naïve notion of an observer wholly isolated from the object of his investigation. However, this volume lacks both originality and subtlety. What is true has been said far better many times before. The author apparently does not understand philosophy sufficiently well to do justice to the range of topics he skips across. He does not properly deal with the value problem in modern science. His
UNCOMMON PYOGENIC INFECTION OF THE MIDDLE EAR.
Authors: ROBERT SATTLER
Journal: JAMA (1900)

It has long been recognized that cauterization of posterior and middle nasal hypertrophies, even if practiced with every caution in the selection of cases, method, and accompanied by every required antiseptic precaution, is not unattended by dangers. This warning is often not heeded until personal observation and experience have afforded convincing proof of its truth. Formerly, when the use of the galvano-cautery and other escharotic methods to effect the shrinkage of the hypertrophied areas of the mucous covering of the inferior turbinates was more general and their application more reckless, it not infrequently came to pass that acute pyogenic infection of the middle ear, of the ethmoidal cells, and even septic infection resulted as a complication in cases even where the operation was clearly indicated and necessary. The destruction of posterior hypertrophy in particular is fraught with risk and danger. Fierce resentment on the part of the cauterized region, altogether
Conrad and Becker’s “10 Criteria” Fall Short of Addressing Conflicts of Interest in Chemical Safety Studies
Authors: Patrice Sutton, Tracey J. Woodruff, Sarah Vogel, Lisa A. Bero
Journal: Environmental Health Perspectives (2011)

on Key Assessment Criteria", Conrad and Becker (2011) proposed the application of 10 criteria to individual studies as a means of assessing a study's "credibility."They characterized the 10 criteria as an "emerging
Mechanism of the Cardiotoxic Actions of Terfenadine
Authors: Raymond L. Woosley
Journal: JAMA (1993)

To gain insight into possible mechanisms of and predisposing factors for torsades de pointes during terfenadine therapy, spontaneous reports in the US Food and Drug Administration's Spontaneous Reporting System database were examined. Based on the characteristics of the cases, in vitro cardiac electrophysiologic studies were conducted to test the hypothesis that terfenadine, and not its major metabolite, has actions similar to those of quinidine and is responsible for this form of cardiac toxicity.Spontaneous reports from the general medical community.As of April 1, 1992, 25 cases of torsades de pointes had been reported to the Food and Drug Administration's Spontaneous Reporting System. Predisposing factors in these cases indicated that the parent drug, but not its metabolite, may have actions similar those of quinidine that are responsible for inducing arrhythmia. In vitro studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes. The metabolite, terfenadine carboxylate, did not inhibit this potassium current even at concentrations 30 times higher than the concentration of terfenadine producing a half-maximal effect.Since blockade of the potassium channel did not occur with the major metabolite of terfenadine, episodes of torsades de pointes are most likely the result of a quinidinelike action of the parent drug and of factors that impair the normally rapid metabolism of terfenadine. Dosage restriction and awareness of the clinical conditions and drug interactions capable of inhibiting the metabolism of terfenadine are essential for prevention of this serious reaction.
Clinical Outcomes of Patients With Severe Aortic Stenosis at Increased Surgical Risk According to Treatment Modality
Authors: Peter Wenaweser, Thomas Pilgrim, Alexander Kadner, Christoph Huber, Stefan Stortecky, Lutz Buellesfeld, Ahmed A. Khattab, Fabienne Meuli, Nadja Roth, Balthasar Eberle, Gabor Erdös, Henriette Brinks, Bindu Kalesan, Bernhard Meier, Peter Jüni, Thierry Carrel, Stephan Windecker
Journal: Journal of the American College of Cardiology (2011)
US changes trade policy on essential medicines
Authors: G. Yamey
Journal: BMJ (1999)

Bill Clinton, the president of the United States, has promised that his government will change its trade policy to support greater access to essential medicines in the developing world.

At the World Trade Organisation ministerial meetings in Seattle, President Clinton said: “The United States will henceforward implement its healthcare and trade policies in a manner that ensures that people in the poorest countries won't have to go without the medicine they …
Toward Better Prescribing — Smoking and Sport — A Committee on Privacy
Authors: John Lister
Journal: New England Journal of Medicine (1972)

THE Drug Industry is, of course, big business, as was well demonstrated in the way that the share prices of three leading drug companies fluctuated during a recent three-cornered takeover battle. This struggle began toward the end of last year, when the drug company Beecham made a takeover bid for the rival Glaxo group, a move that was shortly followed by an announcement that Glaxo and another drug company, Boots, had agreed on terms for an alternative merger. Because of the implications of either a Beecham - Glaxo or a Boots - Glaxo merger, the government ordered the Monopolies Commission . . .
Cardiac dysfunction in portal hypertension among patients with cirrhosis and non-cirrhotic portal fibrosis
Authors: Binay K De, Debabrata Majumdar, Debasish Das, Pranab K Biswas, Sanjay K Mandal, Sujay Ray, Kausik Bandopadhyay, Tapas K Das, Sanjay Dasgupta, Supriya Guru
Journal: Journal of Hepatology (2003)
Treat the worms, but do other things too
Authors: F. Godlee
Journal: BMJ (2012)

More than a third of the world’s population is infested with worms according to the Global Atlas of Helminth Infections (www.thiswormyworld.org). Most of those affected live in extreme poverty in resource poor settings in sub-Saharan Africa, Asia, and the Americas. Children are particularly vulnerable to the ill effects of a heavy parasitic load. As Nigel Hawkes says (doi:10.1136/bmj.e8558), given these facts, who would hesitate to provide the few pennies it costs to deworm a child?

Indeed there is no shortage of international organisations and charities willing to invest in deworming programmes. But, as Hawkes explains, their enthusiasm is based on claims of benefit that …
Innateness, abstract names, and syntactic cues in <i>How Children Learn the Meanings of Words</i>
Authors: Heidi Harley, Massimo Piattelli-Palmarini
Journal: Behavioral and Brain Sciences (2001)

Bloom masterfully captures the state-of-the-art in the study of lexical acquisition. He also exposes the extent of our ignorance about the learning of names for non-observables. HCLMW adopts an innatist position without adopting modularity of mind; however, it seems likely that modularity is needed to bridge the gap between object names and the rest of the lexicon.
Editors' reply to Harris
Authors: Tony Delamothe, Rosamund Snow, Fiona Godlee
Journal: BMJ (2014)

From time to time, The BMJ declares its outright opinion on topical, contentious, and heavily debated areas, and under its current editorship this is unlikely to change.1 2 Examples include our support for the rights of Northern Irish women to abortion,3 and our opposition to the Health …