tbuckley/cabot-search huggingface dataset:
Bile salt–dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans
Authors: Laurence Panicot-Dubois, Grace M. Thomas, Barbara C. Furie, Bruce Furie, Dominique Lombardo, Christophe Dubois
Journal: Journal of Clinical Investigation (2007)

Bile salt-dependent lipase (BSDL) is an enzyme involved in the duodenal hydrolysis and absorption of cholesteryl esters. Although some BSDL is transported to blood, the role of circulating BSDL is unknown. Here, we demonstrate that BSDL is stored in platelets and released upon platelet activation. Because BSDL contains a region that is structurally homologous to the V3 loop of HIV-1, which binds to CXC chemokine receptor 4 (CXCR4), we hypothesized that BSDL might bind to CXCR4 present on platelets. In human platelets in vitro, both BSDL and a peptide corresponding to its V3-like loop induced calcium mobilization and enhanced thrombin-mediated platelet aggregation, spreading, and activated alpha(IIb)beta(3) levels. These effects were abolished by CXCR4 inhibition. BSDL also increased the production of prostacyclin by human endothelial cells. In a mouse thrombosis model, BSDL accumulated at sites of vessel wall injury. When CXCR4 was antagonized, the accumulation of BSDL was inhibited and thrombus size was reduced. In BSDL(-/-) mice, calcium mobilization in platelets and thrombus formation were attenuated and tail bleeding times were increased in comparison with those of wild-type mice. We conclude that BSDL plays a role in optimal platelet activation and thrombus formation by interacting with CXCR4 on platelets.
Measles---a minor childhood illness?
Authors: L. Morrison
Journal: BMJ (2001)

Several weeks ago, the BBC Radio 4 phone-in programme You and Yours tackled the subject of the MMR (measles, mumps, and rubella) vaccine. David Elliman, consultant in community child health at St George's Hospital, London, and author of a BMJ editorial on MMR ( BMJ 2001;322:183-4), was in the studio. There were calls from parents saying that their children had developed autism after having the MMR vaccine, and others from parents who firmly believed that the single vaccine was the way forward. Then a woman rang in to say that she had had measles at the age of 5 and it wasn't such an innocuous disease. She had been deaf ever since. Finally, there was the mother who called to say that her child, who had had the MMR vaccine, was autistic; she believed that the two were completely unconnected.

> Measles is not a trivial illness. If you're unlucky, like Adam, it may take away your life 

I tried to get through to tell them about Adam, but the lines were engaged. Adam was …
Authors' reply to Wardlaw and Berge
Authors: Brian S Alper, Meghan Malone-Moses, James S McLellan, Kameshwar Prasad, Eric Manheimer
Journal: BMJ (2015)

Wardlaw and Berge note the use of data from all thrombolytic trials and alteplase trials, and that distinguishing between these conclusions could be a source of confusion.1 Either way, we question the validity of "up to six hours" or "up to 4.5 hours" conclusions because:
Abstract 3117: COX-2 is a novel transcriptional target of the nuclear EGFR-STAT3 and EGFRvIII-STAT3 signaling axes
Authors: Hui-Wen Lo, Xinyu Cao, Hu Zhu, Francis Ali-Osman
Journal: Cancer Research (2010)

Abstract Emerging evidence indicate novel modes of EGFR signaling, notably, one involves EGFR nuclear translocalization and subsequent gene activation. To date, however, the significance of the nuclear EGFR pathway in glioblastoma (GBM), the most frequent and deadliest brain malignancy in adults, is unknown. Here, we report that EGFR and its constitutively activated variant EGFRvIII undergo nuclear translocalization in GBM cells, in which the former event requires EGF stimulation and the latter is constitutive. To gain insight into the impact of nuclear EGFR on gene expression in GBM, we created isogenic GBM cell lines, namely, U87MG-vector, U87MG-EGFR and U87MG-EGFRdNLS that, respectively, express the control vector, EGFR and nuclear-entry defective EGFR with a deletion of the nuclear localization signal (NLS). Microarray analysis shows that 19 genes, including, cyclooxygenase-2 (COX-2), to be activated in U87MG-EGFR cells but not in U87MG-EGFRdNLS and U87MG-vector cells. Subsequent validation studies indicate that COX-2 gene is expressed at higher levels in cells with EGFR and EGFRvIII than those with EGFRdNLS and EGFRvIIIdNLS. Nuclear EGFR and its transcriptional co-factor STAT3 associate with the COX-2 promoter. Increased expression of EGFR/EGFRvIII and activated STAT3 leads to synergistic activation of the COX-2 promoter. Promoter mutational analysis identified a proximal STAT3-binding site that is required for EGFR/EGFRvIII-STAT3 mediated COX-2 gene activation. In GBM tumors, an association exists between levels of COX-2, EGFR/EGFRvIII and activated STAT3. Together, these findings indicate the existence of the nuclear EGFR/EGFRvIII signaling pathway in GBM and its functional interaction with STAT3 to activate COX-2 gene expression, thus linking EGFR-STAT3 and EGFRvIII-STAT3 signaling axes to pro-inflammatory COX-2 mediated pathway. 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 3117.
communicating risk in the United Kingdom
Authors: M. Powers
Journal: BMJ (2003)

Mazur describes how in the United States clinicians are changing their practices in accordance with what the law demands. In the United Kingdom the medical profession should take the credit for the changes in clinical practice that have driven the law on informed consent. Within certain limits, it is the clinician who decides how and what to impart and, unless there is an adverse outcome, patients are unlikely to complain and cannot sue about inadequate information.

A report by the chief medical officer for England on clinical negligence acknowledges that communication and information sharing has to be improved.1 Exchange and provision of information is at the core of an open and honest relationship between healthcare professionals and patients.2 Mazur questions whether relatives …
Temporal and spatial distribution of interleukin-1β in balloon injured porcine coronary arteries
Authors: J Chamberlain
Journal: Cardiovascular Research (1999)

Interleukin-1 beta (IL-1 beta) is a proinflammatory cytokine with a wide range of biological activities. We determined the distribution of IL-1 beta following percutaneous transluminal coronary angioplasty (PTCA) of porcine arteries, and the presence of caspase-1 (required for the activation of IL-1 beta).Oversized balloon angioplasty was performed in Yorkshire White pigs and the vessels excised at selected intervals (1, 6, 18 h, 3, 7, and 14 days) post-PTCA. IL-1 beta and caspase-1 were then identified using reverse transcription polymerase chain reaction (RT-PCR), in situ RT-PCR, and immunohistochemistry.IL-1 beta protein was detected in the inflammatory infiltrate up to 3 days after PTCA. Luminal endothelial cells contained IL-1 beta at 1 h, with peak expression at 3-7 days. Adventitial capillaries were IL-1 beta-positive at all timepoints. IL-1 beta was detected in adventitial cells at 3 days, with reduced levels at 7 and 14 days. At 7 days, neointimal cells were also IL-1 beta positive. No IL-1 beta was detected in non-PTCA control arteries. RT-PCR demonstrated IL-1 beta mRNA expression to be induced at 1 h, and absent at 3 days. In situ RT-PCR revealed this expression to be distributed throughout the arterial layers at 6 h, but localized to the adventitia at 18 h, with a baseline expression in the adventitial layer of non-PTCA controls. Caspase-1 was detected in luminal endothelial cells from 6 h, in adventitial cells from 3 days, and in neointimal cells from 7 days post-PTCA. This expression colocalized with IL-1 beta, indicating the potential for the IL-1 beta present to become activated.We conclude that IL-1 beta is synthesised, in conjunction with caspase-1, by endothelial, inflammatory, and adventitial cells early (within 3 days) after PTCA, with decreased levels at later timepoints, suggesting that it has a key role to play in the early stages of healing following PTCA.
Adjuvant Therapy for Colon Cancer — The Pace Quickens
Authors: Carmen Allegra, Daniel J. Sargent
Journal: New England Journal of Medicine (2005)

Every year in the United States, approximately 30,000 people receive the diagnosis of lymph-node–positive colon cancer (stage III); worldwide, the number approaches 200,000. The primary therapy for this condition is surgical resection, which cures 50 to 60 percent of patients with average-risk stage III disease.1,2 During the past 15 years, sequential advances in chemotherapy after surgical resection (adjuvant chemotherapy) have had an irrefutable and substantial benefit, with the 4-year rate of overall survival approaching 80 percent.3 In this issue of the Journal, Twelves and colleagues report on the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial, in which 1987 . . .
Correct Name of Malignant Tertian Parasite
Authors: R. Christophers, J. A. Sinton
Journal: BMJ (1938)

the freest drainage will, by hastening resolution, diminish the stubsequent fibrous contractures.It is very desirable that those who are responsible for the treatment during the acuite inflammatory phases should also supervise the subsequent treatment by physiothera- peutic means.While few would challenge the value of complete rest to the part duiring the early acute phase of inflammatory reaction, few would deny the benefits of active movement and of exercise once the florid spreading stage is over and the early dangers are past.Apart from the sloughing of tendons and the involvement of joints which give permanent stiffness, we have the adhesions in tendon sheaths, the fibrosis in the fascial planes between the muscles, the fibrous plaques which form where tissue was destroyed.If the thought of function be kept uppermost in our minds in conducting the treatment in the stages which follow that of the invasive process, we shall never permit the development of the unbreakable barriers to movement which determine crippledom in the neglected case.The use of active and purposive exercise in restoring useful movement should govern the tedious period which follows that of nursing care.Massage and passive exer- cise have their place, but active movement, controlled and guided by the patient's will, is the effective element in treatment.If interest and achievement lend their spur to effort, the patient, progressing from one task to another designed to increase the range of certain movements, passes unconsciously from invalidism back to effective work.The workshop now forms an essential part of the equipment of the convalescent institution.Our responsibility for treatment does not end until the maxi- mum of usefulness has been restored.Summary 1. Acute infections of the hand should be treated in the first instance on conservative lines.2. In very severe infections three measures may be employed: (a) lymph and venous stasis (Bier); (b) chemo- therapy (sulphonamide); (c) passive immunity (antitoxic ser um).3. In certain areas-for example, finger pulp and tendon sheaths-anatomical considerations make early opening desirable.4. As soon as the early dangers are past, efforts to restore function should begin, and they should end only when the maximum return of function that is possible has been attained.At the eleventh British Congress of Obstetrics and Gynaeco- logy, which, as already announced in these columns, is to be held at Edinburgh on April 4, 5, and 6, 1939, the chief subject for discussion will be pain in labour and methods of allevia- tion, to be introduced by Professor Chassar Moir of Oxford and Dr. John Sturrock of Edinburgh.The official guests of the Congress will be Professor Wagner (Berlin) and Dr. Samuel Meaker (Boston).Other communications will deal with genital hypoplasia, dysmenorrhoea, tubal infection,
SPECT myocardial perfusion imaging in women: How critical is choice of radionuclide for attaining optimal results?
Authors: Timothy M. Bateman, Frans J.Th. Wackers, Jennifer H. Mieres, S.James Cullom, Kelly L. Moutray, Ginger K. Hertenstein, Nicole A. Nichols, James A. Case
Journal: Journal of the American College of Cardiology (2003)
Fluorouracil in Pregnancy: Effect on the Neonate
Authors: Harold E. Stadler
Journal: JAMA (1971)

<h3>To the Editor.—</h3> We have been unable to find a case report of fluorouracil intoxication in the neonate when the drug was administered in the treatment of a malignancy of the pregnant subject. <h3>Report of a Case.—</h3> The patient noted a small mass in the left breast during July 1968. Her previous health had been good and she had one child, aged 13 years. On Aug 15, radical mastectomy was performed with a microscopic diagnosis of "adenocarcinoma," but examination of the axillary glands was negative. The diagnosis of pregnancy was made two years later (Aug 14, 1970). On Dec 3, mediastinal lymphadenopathy was noted by x-ray film, and treatment with fluorouracil was instituted intravenously. She received 500 mg on each of the following dates: Dec 8, Dec 11, Dec 14, Dec 17, Dec 18, Dec 22, Dec 28, Jan 10, 1971, Jan 12, Jan 15, Jan 29, Feb 6, Feb
A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population
Authors: Tarja Laitinen, Mark J. Daly, John D. Rioux, Paula Kauppi, Catherine Laprise, Tuula Petäys, Todd Green, Michele Cargill, Tari Haahtela, Eric S. Lander, Lauri A. Laitinen, Thomas J. Hudson, Juha Kere
Journal: Nature Genetics (2001)
Treatment of actinomycetoma due to Nocardia spp. with amoxicillin?clavulanate
Authors: A. Bonifaz, P. Flores, A. Saúl, E. Carrasco-Gerard, R.M. Ponce
Journal: British Journal of Dermatology (2006)

Background Actinomycetoma is a chronic occupational condition that occurs frequently in tropical regions. In Mexico 85% of cases are caused by Nocardia brasiliensis. There are two treatments of choice for these cases: a regimen of dapsone plus trimethoprim–sulfamethoxazole (co-trimoxazole) and, recently, amikacin, either alone or combined. However, not all cases respond properly to these therapies. Objectives To report a retrospective, 11-year study of cases of actinomycetomas caused by Nocardia spp., treated with amoxicillin–clavulanate (co-amoxiclav). Methods All cases were identified clinically and microbiologically and had previously failed standard therapies. Oral co-amoxiclav 875/125 mg was administered every 12 h. Clinical, microbiological and laboratory follow up was performed every 2 months during the treatment period. Results Twenty-one cases of actinomycetoma were included, 19 caused by N. brasiliensis and one each by N. asteroides and N. otitidiscaviarum. Clinical and microbiological cure occurred in 15 of 21 cases (71%); two cases improved (10%) and four failed (19%). Mean treatment period was 9·6 months, during which neither side-effects nor laboratory test alterations were reported. Conclusions Treatment with co-amoxiclav represents an alternative or rescue treatment for cases that have previously failed standard therapies.
Mutant deoxynucleotide carrier is associated with congenital microcephaly
Authors: Marjorie J. Rosenberg, Richa Agarwala, Gerard Bouffard, Joie Davis, Giuseppe Fiermonte, Mark S. Hilliard, Thorsten Koch, Linda M. Kalikin, Izabela Makalowska, D. Holmes Morton, Elizabeth M. Petty, James L. Weber, Ferdinando Palmieri, Richard I. Kelley, Alejandro A. Schäffer, Leslie G. Biesecker
Journal: Nature Genetics (2002)
Dilemmas in Treating Smoldering Multiple Myeloma
Authors: Inhye E. Ahn, Sham Mailankody, Neha Korde, Ola Landgren
Journal: Journal of Clinical Oncology (2014)

Novel therapies hold promise for high-risk smoldering multiple myeloma (SMM). Recent studies suggest that modern combination approaches can be options for high-risk SMM to obtain deep molecular responses with favorable toxicity profiles. Although pioneering treatment trials based on small numbers of patients suggest progression-free and overall survival benefits, application of the data to real-life practice remains to be validated. Therapeutic modulation of disease tempo, disease burden, clonal evolution, and tumor microenvironment in SMM remains to be understood and calls for reliable biomarkers reflective of disease biology. Here, we review studies that open a new management platform for SMM, address ongoing dilemmas in practice and under investigation, and highlight emerging scientific questions in the era of SMM treatment.
Differential electrocardiographic effects of myocardial ischemia induced by atrial pacing in dogs with various locations of coronary stenosis.
Authors: D M Mirvis
Journal: Circulation (1983)

The spatial distribution of abnormal repolarization potentials caused by regional myocardial ischemia was determined in 45 dogs. Ameroid constrictors were placed around the left circumflex artery in 10, the left anterior descending artery in 10, and the right coronary artery in 10. Ten dogs without constrictors served as controls. Electrocardiographic events were determined from body surface isopotential distributions, which were computed from potentials sensed by 84 torso electrodes. In control dogs, pacing to heart rates of 230 to 250 beats/min increased the intensity of positive and negative surface extrema during the ST segment without altering their spatial features. Two weeks after placement of the ameroid constrictors, tachycardia induced abnormal negative potentials during the ST segment. Localization of these ischemic forces varied with the placement of the constrictor in a manner consistent with the affected perfusion territories. However, much of the torso surface was involved by all lesions, and only small zones of ST segment depression unique to specific lesions could be identified. In five additional dogs a constrictor was placed on the right coronary artery 3 months after implantation of a device on the circumflex vessel. ST segment patterns during pacing in dogs with two lesions were consistent with the sum of the two individual lesions. Thus, the regional nature of myocardial ischemia is detectable in the body surface isopotential distributions, but the degree of spatial overlap may limit the value of such techniques in extending the usefulness of clinical exercise-stress electrocardiography.
Hazards of blood splashes.
Authors: M J Porteous
Journal: BMJ (1990)

When encountering novel environments, animals perform complex yet structured exploratory behaviors. Despite their typical structuring, the principles underlying exploratory patterns are still not sufficiently understood. Here we analyzed exploratory behavioral data from two modalities: whisking and locomotion in rats and mice. We found that these rodents maximized novelty signal-to-noise ratio during each exploration episode, where novelty is defined as the accumulated information gain. We further found that these rodents maximized novelty during outbound exploration, used novelty-triggered withdrawal-like retreat behavior, and explored the environment in a novelty-descending sequence. We applied a hierarchical curiosity model, which incorporates these principles, to both modalities. We show that the model captures the major components of exploratory behavior in multiple timescales: single excursions, exploratory episodes, and developmental timeline. The model predicted that novelty is managed across exploratory modalities. Using a novel experimental setup in which mice encountered a novel object for the first time in their life, we tested and validated this prediction. Further predictions, related to the development of brain circuitry, are described. This study demonstrates that rodents select exploratory actions according to a novelty management framework and suggests a plausible mechanism by which mammalian exploration primitives can be learned during development and integrated in adult exploration of complex environments.
Air pollution in homes
Authors: D. Coggon
Journal: BMJ (1996)

The dangers of air pollution are a regular topic of discussion in the lay press, much of it ill informed. For example, the increasing prevalence of asthma in Britain and elsewhere is widely attributed to the rise in pollutants from motor vehicles, although the balance of scientific evidence suggests that any influence of traffic pollutants on the initiation of asthma is small.1 Traffic pollutants, especially fine particulates, do seem to cause illness, but their impact on public health is probably less than that of smoking, diet, and poor housing.

To date, attention has focused mainly on pollutants in outdoor air, for which it is easy to blame others rather than ourselves. Indoor hazards that have attracted publicity have also tended to be those caused by someone else—such as asbestos in schools and council flats or …
Atypical Carcinoid Tumor of the Lung: A Surveillance, Epidemiology, and End Results Database Analysis
Authors: Conor E. Steuer, Madhusmita Behera, Sungjin Kim, Zhengjia Chen, Nabil F. Saba, Rathi N. Pillai, Taofeek K. Owonikoko, Fadlo R. Khuri, Suresh S. Ramalingam
Journal: Journal of Thoracic Oncology (2014)
The Sicilian Gambit and antiarrhythmic drug development
Authors: T. J Colatsky
Journal: Cardiovascular Research (1992)

Journal Article The Sicilian Gambit and antiarrhythmic drug development Get access Thomas J Colatsky Thomas J Colatsky Division of Cardiovascular and Metabolic Disorders, Wyeth-Ayerst Research, CN 8000, Princeton, NJ 08453, USA: T J Colatsky. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 6, June 1992, Pages 562–565, https://doi.org/10.1093/cvr/26.6.562 Published: 01 June 1992 Article history Received: 31 January 1992 Accepted: 09 March 1992 Published: 01 June 1992
Attributability of death to pneumoconiosis in beneficiaries
Authors: R. L. Sadler
Journal: Thorax (1974)

<b>Sadler, R. L. (1974).</b><i>Thorax</i>, <b>29</b>, 699-702. <b>Attributability of death to pneumoconiosis in beneficiaries.</b> Coal workers and slate workers who were receiving in 1965 industrial disability benefit for pneumoconiosis were grouped according to the radiological extent of their disease and their disability assessment. They were followed up for 7·5 years. Standard mortality rates, and from these the percentage of all deaths which can be attributed to pneumoconiosis, were assessed. About 10% of the deaths in the coal workers and about 40% of those in the slate workers were found to be accelerated by their pneumoconiosis, the proportion varying directly with the radiological extent of the disease and with the disability assessment at the beginning of the survey.
Book Review Human Dignity and Bioethics: Essays Commissioned by the President's Council on Bioethics By Adam Schulman, F. Daniel Davis, and Daniel C. Dennett, with 20 others. 555 pp. Washington, DC, The President's Council on Bioethics, 2008. $49. 978-0-16-080071-9 ; Government Printing Office Stock Number 017-023-00218-0.
Authors: Leslie A. Meltzer
Journal: New England Journal of Medicine (2008)