tbuckley/cabot-search huggingface dataset:
RANTES Deposition by Platelets Triggers Monocyte Arrest on Inflamed and Atherosclerotic Endothelium
Authors: Philipp von Hundelshausen, Kim S. C. Weber, Yuqing Huo, Amanda E. I. Proudfoot, Peter J. Nelson, Klaus Ley, Christian Weber
Journal: Circulation (2001)

Background —Circulating platelets and chemoattractant proteins, such as the CC chemokine RANTES, contribute to the activation and interaction of monocytes and endothelium and may thereby play a pivotal role in the pathogenesis of inflammatory and atherosclerotic disease. Methods and Results —The binding of RANTES to human endothelial cells was detected by ELISA or immunofluorescence after perfusion with platelets or exposure to their supernatants. Monocyte arrest on endothelial monolayers or surface-adherent platelets was studied with a parallel-wall flow chamber and video microscopy. We show that RANTES secreted by thrombin-stimulated platelets is immobilized on the surface of inflamed microvascular or aortic endothelium and triggers shear-resistant monocyte arrest under flow conditions, as shown by inhibition with the RANTES receptor antagonist Met-RANTES or a blocking RANTES antibody. Deposition of RANTES and its effects requires endothelial activation, eg, by interleukin-1β, and is not supported by venous endothelium or adherent platelets. Immunohistochemistry revealed that RANTES is present on the luminal surface of carotid arteries of apolipoprotein E–deficient mice with early atherosclerotic lesions after wire-induced injury or cytokine exposure. In a mechanistic model of atherogenesis, monocyte adherence on endothelium covering such lesions was studied in murine carotid arteries perfused ex vivo, showing that the accumulation of monocytic cells in these carotid arteries involved RANTES receptors. Conclusions —The deposition of RANTES by platelets triggers shear-resistant monocyte arrest on inflamed or atherosclerotic endothelium. Delivery of RANTES by platelets may epitomize a novel principle relevant to inflammatory or atherogenic monocyte recruitment from the circulation.
Marketing to register organ donors may circumvent principles of informed consent
Authors: E. Milligan, S. Winch, R. Adams
Journal: BMJ (2012)

Organ donation and transplantation are seen as indisputable medical successes that are a communal moral good. Twin themes dominate the public debate: low organ supply is creating a preventable health tragedy, and increasing supply will solve the growing problem of organ failure. Health education and marketing campaigns to boost donation rates accompany the public debate, and they typically use emotive and persuasive language (“gifts of life”; “joy from tragedy”) to assert the worth of donation and transplantation. Ultimately, their aim is to secure advance consent from potential organ donors through registries.1

Current and prospective medical decision making relies on five well established criteria: competency; disclosure of material information; optional and voluntary participation; understanding the nature, risks, and benefits; and participation without coercion. Together these criteria form the doctrine of informed consent that lends ethical legitimacy to healthcare interventions through respecting patient autonomy.2 For posthumous organ donation, consent is sought from the dead person’s substitute decision maker at the time of organ harvesting. The donor registry indicates the wishes of the dead person and so provides a form of advance consent.

Increasing donor registrations through marketing campaigns …
Two visual hallucinatory syndromes
Authors: Dominic H. ffytche
Journal: Behavioral and Brain Sciences (2005)

When viewed from a distance, visual hallucinations fall into one of two symptom patterns, a dichotomy which poses a problem for theoretical models treating them as a single entity. Such models should be broadened to allow for two distinct but overlapping syndromes – one likely to relate to visual de-afferentation, the other to Perception and Attention Deficit (PAD) cholinergic pathology.
Inflammatory bowel disease reveals the kinase activity of KSR1
Authors: Richard Kolesnick, H. Rosie Xing
Journal: Journal of Clinical Investigation (2004)

Kinase suppressor of Ras-1 (KSR1) is a recently identified member of the EGFR-Ras-Raf-1-MAPK signaling pathway. A new study demonstrates that KSR1 protects intestinal epithelium from TNF-alpha-induced apoptosis, abrogating inflammatory bowel disease (IBD). Since its discovery, there has been disagreement as to whether KSR1 possesses intrinsic kinase activity. Using transgenic mouse models and genetically modified mouse colon epithelial cells, Polk and coworkers show that the kinase activity of KSR1 is off in normal colon epithelial cells, becoming activated only at the onset of IBD. They also provide strong evidence that KSR1 kinase activity is essential for anti-apoptotic protection of the intestinal epithelium. These new data in support of KSR1 as a kinase highlight an ongoing debate as to whether KSR1 does indeed serve as a specific kinase in transphosphorylating and transactivating c-Raf-1 toward MEK1.
American Paragonimiasis Treated with Praziquantel
Authors: Constance T. Pachucki, Roland A. Levandowski, Valerie A. Brown, Brigitta H. Sonnenkalb, Michael J. Vruno
Journal: New England Journal of Medicine (1984)

PARAGONIMUS species native to the United States have been found commonly in animals.1 , 2 However, unlike the human illness associated with Paragonimus westermani in Asia, infection acquired in North or South America has rarely been documented in human beings.1 2 3 We report on a patient who was infected with a paragonimus species after eating raw crayfish in Missouri. The symptoms of his illness were typical of paragonimiasis. Treatment with praziquantel, a new tremalodicide,4 5 6 resulted in prompt resolution of the illness, with no adverse effects. The epidemiology of infection with American paragonimus species and related intermediate hosts suggests that physicians throughout the United . . .
Colonic Villous Adenoma
Authors: Curtis C. Adolphson
Journal: JAMA (1982)

A colonic villous adenoma removed from a glucose-6-phosphate dehydrogenase (G6PD) heterozygous patient was studied. The mucosal cells were separated to eliminate the contaminating nonadenoma cells by enzymatic disaggregation followed by isokinetic gradient centrifugation. The mucosal cells from this colonic polyp contained a single G6PD isoenzyme. Our study demonstrates clonality of this type of polyp and the value of the cell separation techniques in the experimental oncology. (<i>JAMA</i>1982;247:829-830)
High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas
Authors: Maria Raffaella Zocchi, Silvia Catellani, Paolo Canevali, Sara Tavella, Anna Garuti, Barbara Villaggio, Annalisa Zunino, Marco Gobbi, Giulio Fraternali-Orcioni, Annalisa Kunkl, Jean-Louis Ravetti, Silvia Boero, Alessandra Musso, Alessandro Poggi
Journal: Blood (2011)
PWE-085 Audit Of Outcomes Of A Managed 5 Asa Switching Program
Authors: N Taylor, D Chan, J Bowey, F Cummings
Journal: Gut (2014)

<h3>Introduction</h3> 5-aminosalicylic acid (5-ASA) preparations are used to induce and maintain remission in ulcerative colitis (UC). The cost of the recommended maintenance dose for oral 5ASA preparations varies from 86p and 208p per day (MIMMS 2011). Switching to cheaper 5ASAs has been suggested as a possible drug cost saving. The BNF states that preparations are not interchangeable but with little direct evidence to support this statement. The aim of this pilot study is to gain preliminary data on a primary care based 5ASA switching programme. <h3>Methods</h3> Salofalk granules (Dr Falk Pharma) and Pentasa (Ferring Pharmaceuticals) were identified as the cheapest 5ASA items prescribed in 31 GP practices. An initial pilot study in one practice revealed that only 5/21 patients responded to a written invitation alone and successfully switched to Salofalk. We therefore developed a managed programme utilising a community based gastroenterology nurse specialist in 4 other practices. A written invitation detailing the rationale for switching 5-ASA was sent to all appropriate patients who were then phoned a week later. If patients agreed to the switch, the GP surgery was contacted by the Nurse Specialist to change the repeat prescription. Patients were switched to Salofalk in 2 practices and Pentasa in the other 2. GP and hospital records were then examined 6 months post-switch to assess for evidence of patient acceptability and tolerability. <h3>Results</h3> 120 patients (56 male, 64 female) with a mean age of 50 years were identified as being on a 5-ASA preparation (oral or topical). 56 (47%) were under either virtual or hospital gastroenterology follow-up. 64 patients with ulcerative colitis were taking oral 5-ASAs. 21 (33%) were already taking Salofalk or Pentasa. Of the remaining 43 patients, 24 (56%) agreed to the switch, 10 (23%) declined, and 9 (21%) did not respond to the invitation or telephone call. Of the 24 patients who agreed to switch, only 17 (71%) completed the process. 15 (88%) remained on the new 5-ASA for at least 6 months, with reasons for discontinuation cited as preference for the previous preparation or diarrhoeal symptoms. <h3>Conclusion</h3> Conducting a managed 5ASA switching programme is feasible with 17/43 eligible patients successfully switched with 15/17 continuing on these preparations. Areas for development include following up patients who initially agreed but failed to switch, recording more robustly any flares, involving secondary physicians and assessing adherence and cost savings. This study provides preliminary evidence to develop a large scale study in this important area. <h3>Disclosure of Interest</h3> N. Taylor: None Declared, D. Chan: None Declared, J. Bowey: None Declared, F. Cummings Speaker bureau with: Ferring Pharmaceuticals, Conflict with: Advisory board and educational support Ferring Pharmaceuticals. Educational support: Dr Falk, Warner Chilcott and Shire.
De novo acute nonlymphoblastic leukemia (M5b) having a chromosomal 3;21 translocation with immunoglobin heavy-chain gene rearrangement
Authors: Hiroyasu Kaya, Keiji Aoshima, Kazuhiro Okafuji, Nobuyoshi Tanaka, Shigeki Ohtake, Shinobu Nakamura, Tamotsu Matsuda
Journal: American Journal of Hematology (1996)
Apply criteria to improve health systems in developing countries
Authors: D. Beran, J. S. Yudkin
Journal: BMJ (2012)

Shelton proposes 20 criteria to make the best use of scarce resources in developing countries.1 This new approach to prioritising healthcare interventions may, however, omit considerations strengthening health services as well as some ethical issues.

We have scored insulin use in type 1 diabetes in a typical resource poor setting. With a score of around 70-80, this intervention would be …
The woodchuck interferon alpha system: cloning, family description and biologic activity
Authors: Pedro Berraondo, Raquel Garcia-Navarro, Gloria Gonzalez-Aseguinolaza, Africa Vales, Laura Ochoa, Begona Blanco-Urgoiti, Esther Larrea, Jose Ignacio Riezu, Jesus Prieto, Juan Ruiz
Journal: Journal of Hepatology (2002)
Enzymatically degradable temperature-sensitive polypeptide as a new in-situ gelling biomaterial
Authors: Yuri Jeong, Min Kyung Joo, Kyung Hyun Bahk, Yun Young Choi, Ho-Tae Kim, Won-Ki Kim, Hwa Jeong Lee, Youn Soo Sohn, Byeongmoon Jeong
Journal: Journal of Controlled Release (2009)
LIMD2 Is a Small LIM-Only Protein Overexpressed in Metastatic Lesions That Regulates Cell Motility and Tumor Progression by Directly Binding to and Activating the Integrin-Linked Kinase
Authors: Hongzhuang Peng, Mehdi Talebzadeh-Farrooji, Michael J. Osborne, Jeremy W. Prokop, Paul C. McDonald, Jayashree Karar, Zhaoyuan Hou, Mei He, Electron Kebebew, Torben Orntoft, Meenhard Herlyn, Andrew J. Caton, William Fredericks, Bruce Malkowicz, Christopher S. Paterno, Alexandra S. Carolin, David W. Speicher, Emmanuel Skordalakes, Qihong Huang, Shoukat Dedhar, Katherine L.B. Borden, Frank J. Rauscher
Journal: Cancer Research (2014)

Proteins that communicate signals from the cytoskeleton to the nucleus are prime targets for effectors of metastasis as they often transduce signals regulating adhesion, motility, and invasiveness. LIM domain proteins shuttle between the cytoplasm and the nucleus, and bind to partners in both compartments, often coupling changes in gene expression to extracellular cues. In this work, we characterize LIMD2, a mechanistically undefined LIM-only protein originally found to be overexpressed in metastatic lesions but absent in the matched primary tumor. LIMD2 levels in fresh and archival tumors positively correlate with cell motility, metastatic potential, and grade, including bladder, melanoma, breast, and thyroid tumors. LIMD2 directly contributes to these cellular phenotypes as shown by overexpression, knockdown, and reconstitution experiments in cell culture models. The solution structure of LIMD2 that was determined using nuclear magnetic resonance revealed a classic LIM-domain structure that was highly related to LIM1 of PINCH1, a core component of the integrin-linked kinase-parvin-pinch complex. Structural and biochemical analyses revealed that LIMD2 bound directly to the kinase domain of integrin-linked kinase (ILK) near the active site and strongly activated ILK kinase activity. Cells that were null for ILK failed to respond to the induction of invasion by LIMD2. This strongly suggests that LIMD2 potentiates its biologic effects through direct interactions with ILK, a signal transduction pathway firmly linked to cell motility and invasion. In summary, LIMD2 is a new component of the signal transduction cascade that links integrin-mediated signaling to cell motility/metastatic behavior and may be a promising target for controlling tumor spread.
The economy of the columnar epithelial cell.
Authors: D H Smyth
Journal: Gut (1969)

The economy of the columnar epithelial cell 'Entia non sunt multiplicanda sine necessitate' said William of Occam, and it has always been a laudable aim of science to explain experimental findings and observations with the fewest and simplest hypotheses.The intestinal epithelial cell has undoubtedly a multi- plicity of functions even if only the absorptive activities are included" 2'3 and much ingenuity has been used in the past decade to explain how these functions are carried out.The most striking of these activities are the high degree of selectivity the cells exert on what is transferred, the ways in which large hydrophilic molecules pass through a membrane which is at least partly lipid, the electrical phenomena associated with transfer of non-electrolytes and the general problem of how the colum- nar cell acts as a transducer in converting metabolic energy to osmotic work.Is it possible to find some one basic mechanism which could underlie all these processes and which could be applied to intestinal absorption of chemically unrelated groups of substances?Any attempt to do this is an aim worth pursuing.It involves first careful thinking about the definition of active transfer by the intestine.A common view is that active transfer is movement of a substance against its electrochemical potential, and substances which do not exhibit this feature are regarded as being transferred passively.Another view is that processes showing 'saturation kinetics' are active, while those showing 'diffusion kinetics' are passive.These views con- tain some serious fallacies not always appreciated, and these fallacies are of two kinds: (1) failure to recognize an active component which exists, and (2) postulation of an active process which does not exist.The first is more simply dealt with.If an absorption process shows diffusion kinetics, ie, the rate of absorption is proportional to con- centration, this does not necessarily mean that no active process is involved.It can either mean that the active process is not the rate- limiting stage in a series of processes, or alternatively, the process is functioning very much below its maximum capacity.Furthermore, the fact that a substance moves downhill does not imply that no other driving force is being used.Probably no reader of this article normally relies on the favourable road gradient to propel his car downhill.The second fallacy, ie, unnecessary postulation of an active process, is of a more subtle kind.Let us oversimplify the problem by regarding the intestinal epithelial cell layer as a membrane separating two com- partments and able to move substances from one to the other.If we simplify the system still further and consider that only one solute (and no solvent) is being transferred, the concept of active transfer is easy and the work done in transfer can be calculated from the concentration 2 on August 13,
Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice
Authors: Jennifer N. Lilla, Ching-Cheng Chen, Kaori Mukai, Maya J. BenBarak, Christopher B. Franco, Janet Kalesnikoff, Mang Yu, Mindy Tsai, Adrian M. Piliponsky, Stephen J. Galli
Journal: Blood (2011)
The Cabalist: Carpy Regurgitations Concerning the Antepenultimate
Authors: R. Thomas Bergeron
Journal: JAMA (1988)

<h3>To the Editor. —</h3> A glance at the title of your May 27th A PIECE OF MY MIND essay by Dr LaCombe<sup>1</sup>—"The Cabalist"—hints that we have a wordsmith here with considerable affection for<i>language</i>. What a minor disappointment, then, that Dr LaCombe appears to misuse the word<i>penultimate</i>in the latter part of the piece. In the context of the article, it would seem that Dr LaCombe wished to express<i>ultimate</i>in its most superlative sense (ie, the most ultimate diagnostic tool). He chose the word<i>penultimate</i>to express this.<i>Penultimate</i>, however, comes from the Latin<i>paenultima</i>, "penult," and means one step removed from, really one step less than, the final or "ultimate" anything in a progression. Dr LaCombe therefore seems to have missed his ultimate linguistic mark (but just by one). Lest anyone cast a fishy eye at this carping, let it be known that as a
Bronchodilator effects of antiasthmatic cigarette smoke (Datura stramonium).
Authors: D Charpin, J Orehek, J M Velardocchio
Journal: Thorax (1979)

In 12 asthmatic patients with mild airway obstruction we have measured the effect on specific airway resistance (sRaw) of inhaling the smoke of one Datura stramonium cigarette. In 11 patients sRaw decreased substantially after the cigarette, the mean maximal decrease being 40% at the 30th minute. In seven patients the subsequent inhalation of 200 micrograms salbutamol caused no further decrease in sRaw. In the remaining four patients salbutamol induced a larger decrease in sRaw than the cigarette smoke. The inhalation, however, of a synthetic anticholinergic agent (SCH 1000, 600 micrograms) proved as effective as salbutamol in these patients. In one patient the cigarette smoke and SCH 1000 produced only a negligible amount of bronchodilatation whereas the bronchial obstruction was reversible with salbutamol. Minor side effects were observed in six patients after the cigarette.
Chromosome Studies in Agammaglobulinaemic Subjects
Authors: Y. R. Ahuja, H. Fudenberg
Journal: BMJ (1965)

my own experience a request for the estimation of amphetamine in urine is disconcerting to the biochemistry department of even major teaching hospitals and quite beyond the capacity and experience of most other laboratories.I would be very interested to hear the feelings of psychiatrists about these points.-I am, etc.,
Comparative Study of Smoking Habits of Physicians
Authors: Leonid S. Snegireff, Olive M. Lombard
Journal: New England Journal of Medicine (1955)

THE need for current data on smoking to serve as a base line for future comparisons is obvious, and the saying, "physician know thyself," applies to this effort.Most of the tobacco today is derived from Nicotiana tabacum, a plant that is native to South America and Mexico. Before Columbus, N. rustica was commonly smoked by the Indians of Eastern North America whereas N. attenuata, N. quadrivolvis and N. trigonophylla were the popular plants with the Indian tribes of the West.Since John Rolfe began tobacco culture in Jamestown, Virginia, in 1612, the actual processing of tobacco for smoking . . .
The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol
Authors: F. Grønhøj Larsen, P. Jakobsen, C. Grønhøj Larsen, M. Heidenheim, E. Held, F. Nielsen-Kudsk
Journal: British Journal of Dermatology (2009)

Background Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4‐oxo‐isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half‐life. Objectives To determine if isotretinoin (13‐cis‐RA), its main metabolite 4‐oxo‐isotretinoin (4‐oxo‐13‐cis‐RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4‐oxo metabolite were determined. Patients/methods Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self‐administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4‐oxo‐isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse‐phase high‐performance liquid chromatography. Results Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4‐oxo metabolite or the all‐trans compounds was chromatographically detectable in any of the patients’ plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies. Conclusions The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long‐term isotretinoin treatment. After ceasing long‐term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.
Surveillance of Nosocomial Infections by Antibiotic Monitoring
Authors: Lynn Feldman
Journal: JAMA (1979)

Records of all patients receiving intravenous gentamicin sulfate during a 92-day interval were reviewed to detect nosocomial infections that had been missed by routine surveillance. Only 46 of 48 of the 99 treatment courses had been detected. In 96% of cases not detected by routine surveillance, use of gentamicin was considered justified. Of the patients missed by surveillance, 83% were in oncology wards, and 46% had severe neutropenia and fever of unknown origin. Antibiotic surveillance proved a useful adjunct in estimating the incidence of nosocomial infections in such patients.