tbuckley/cabot-search huggingface dataset:
Research ethics have not “sunk to an all time low”
Authors: Geoff Watts
Journal: BMJ (2007)

Clinical researchers working on new drugs were “cleared” last week of allowing their ethical standards to sink to an all time low, in a debate held at a conference on clinical research at the Royal College of Physicians in London.

A small majority of the audience worked in the drug industry, and although the debate was not limited to research within the industry the convincing win must have cheered those in the drug business, who feel that they have recently been under attack. 

The contestants in the debate, entitled “This house believes that the ethics of clinical research have reached an all time low,” were Richard Smith, former editor of the BMJ and now executive director at UnitedHealth Europe, who argued for the motion, and Trevor Jones, former director general of the Association of the British Pharmaceutical Industry.

Dr Smith's first example of unethical behaviour by researchers inside and outside the drug industry was drawn from studies of inappropriate authorship. He said that it was not uncommon …
Oncostatin <scp>M</scp> is a <scp>FIP</scp>1L1/<scp>PDGFRA</scp>‐dependent mediator of cytokine production in chronic eosinophilic leukemia
Authors: G. Hoermann, S. Cerny‐Reiterer, I. Sadovnik, L. Müllauer, M. Bilban, M. Gröger, H.‐P. Horny, A. Reiter, A. Schmitt‐Graeff, C. Mannhalter, P. Valent, M. Mayerhofer
Journal: Allergy (2013)

Chronic eosinophilic leukemia (CEL) is a myeloproliferative neoplasm characterized by expansion of neoplastic eosinophils, tissue infiltration, and organ damage. In a subset of these patients, the FIP1L1/PDGFRA (F/P) oncoprotein is detectable. F/P exhibits constitutive tyrosine kinase activity and activates a number of signaling pathways. So far, however, little is known about the role of F/P-dependent proteins in the pathogenesis of CEL.A screen for F/P-dependent cytokines was performed in growth factor-dependent human cell lines lentivirally transduced with F/P. Signal transduction pathways were characterized in Ba/F3 cells with doxycycline-inducible expression of F/P and in EOL-1 cells. Cytokine expression was confirmed in patients' material by immunohistochemistry, immunofluorescence, and confocal microscopy. Gene expression analysis, proliferation assays, and chemotaxis assays were used to elucidate paracrine interactions between neoplastic eosinophils and stromal cells.We show that F/P upregulates expression of oncostatin M (OSM) in various cell line models in a STAT5-dependent manner. Correspondingly, neoplastic eosinophils in the bone marrow were found to overexpress OSM. OSM derived from F/P + cells stimulated proliferation of stromal cells. Moreover, OSM-containing supernatants from F/P + cells were found to upregulate production of stromal cell-derived factor-1 (SDF-1)/CXCL12 in human fibroblasts. SDF-1, in turn, induced migration of EOL-1 cells in a dose-dependent manner.We have identified a F/P-driven paracrine interaction between neoplastic eosinophils and stromal cells that may contribute to tissue fibrosis and accumulation of neoplastic eosinophils in CEL.
Abstract 3055: PD-0332991, a selective cyclin-dependent-kinase 4/6 Inhibitor, upregulates multiple genes promoting invasion and metastasis in pancreatic ductal adenocarcinoma
Authors: Fang Liu, Murray Korc
Journal: Cancer Research (2012)

Abstract Deregulation of the Cyclin D-CDK4/6-Rb-E2F signaling pathway is among the most commonly found aberrations in human pancreatic ductal adenocarcinoma (PDAC). PD-0332991 is an orally available, highly specific and reversible inhibitor for Cdk4 and Cdk6, and demonstrates in vitro and in vivo growth inhibitory effects in multiple tumor types. However, the potential usefulness of PD-0332991 in PDAC is currently unknown. In this study, we examined the effects of PD-0332991 on multiple human pancreatic cancer cell lines, and we found that this agent inhibited Rb phosphorylation and E2F target gene expression, and induced G0/G1 cell cycle arrest. However, the growth inhibitory effect was only transient, due to the rapidly emerging compensatory changes of the G1/S machinery components, including upregulation of CyclinD1, Cdk4, and Cdk6, and downregulation of Rb, p107, and p130. Microarray analysis revealed that incubation with PD-0332991 upregulated multiple genes which promote pancreatic cancer invasion, metastasis, angiogenesis, and chemoresistance, including LAMC2, CYR61, SERPINE1, F3, ABCA1, ASNS, and DUSP1. In addition, using matrigel-coated transwell invasion chambers, we demonstrated that incubation with PD-0332991 enhanced the invasiveness of human pancreatic cancer cells. These observations suggest that PD-0332991 may have the potential to cause deleterious effects in PDAC by modulating gene expression in a manner that could promote cancer spread, metastasis, and chemoresistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3055. doi:1538-7445.AM2012-3055
Perirenal Hemangiopericytoma
Authors: Robert Simon, Ralph C. Greene
Journal: JAMA (1964)

SPONTANEOUS HYPOGLYCEMIA due to large nonpancreatic neoplasms has been recognized since 1930 when it was described by Anderson<sup>1</sup>and by Doege.<sup>2</sup>The relationship between these tumors and hypoglycemia still remains obscure. The following case is that of a perirenal hemangiopericytoma associated with symptomatic hypoglycemia. <h3>Report of a Case</h3> An 18-year-old male was admitted to Holy Family Hospital on the afternoon of Dec 1, 1961. He had been found in bed late that morning, poorly responsive and disoriented. That evening, except for some dizziness and slight headache, he felt well. He was fully aware of his surroundings but did not recall the earlier events of the day, including his trip to the hospital. In November, 1960, an exploratory laparotomy was done for a possible ruptured spleen, but only a contusion of the abdominal wall was found. For eight months prior to his admission he had headaches of increasing frequency,
Selective perfusion of ischemic myocardium during coronary venous retroinjection: A study of the causative role of venoarterial and venoventricular pressure gradients
Authors: Malte Meesmann, Hrayr S. Karagueuzian, Takeshi Ino, Michael F. Mcgrath, Michael C. Fishbein, William J. Mandel, Thomas Peter
Journal: Journal of the American College of Cardiology (1987)
Delayed Cutaneous Hypersensitivity to Leukocytes in Disseminated Lupus Erythematosus
Authors: Eli A. Friedman, Wadi A. Bardawil, John P. Merrill, Colette Hanau
Journal: New England Journal of Medicine (1960)

RECENT work from this laboratory indicates that patients who have rejected skin homografts manifest a "delayed" type of hypersensitivity to homologous leukocytes. This is evidenced by typical erythema and induration at the local site of an intradermal injection of leukocytes obtained from the peripheral blood of donors.1 Since both the rejection of a skin homograft and the manifestations of disseminated lupus erythematosus may be mediated through "antitissue antibodies" this work was extended to patients with the disease.A patient receiving intramuscular leukocyte injections as therapy for disseminated lupus2 was found to have a strongly positive test to intradermally administered leukocytes. . . .
Pak1 regulates multiple c-Kit mediated Ras-MAPK gain-in-function phenotypes in Nf1+/− mast cells
Authors: Andrew S. McDaniel, Jayme D. Allen, Su-Jung Park, Zahara M Jaffer, Elizabeth G. Michels, Sarah J. Burgin, Shi Chen, Waylan K. Bessler, Clemens Hofmann, David A. Ingram, Jonathan Chernoff, D. Wade Clapp
Journal: Blood (2008)
Continuity and good management are key to better health outcomes in poor countries
Authors: J. Wise
Journal: BMJ (2011)

<h3>Abstract</h3> Action potentials in mesostriatal dopamine (DA) neurons encode the motivational value of salient stimuli. DA neurons possess extensively branched axonal arbours, and how action potentials are converted to DA output will be influenced dynamically and critically by axonal mechanisms that are poorly understood. We explored the role for mechanisms governing release probability and axonal excitability in determining short-term plasticity (STP) of DA release, using fast-scan cyclic voltammetry in <i>ex vivo</i> mouse striatum. The brief short-term facilitation (STF) and longer short-term depression (STD) seen were only weakly dependent on initial release. Rather, STP was strongly governed by release-independent mechanisms that involved K+-dependent axonal excitability and surprisingly, the dopamine transporter (DAT), particularly in dorsal striatum. The DAT acts as a master regulator of DA STP, governing the balance between release-dependent and release-independent mechanisms that also show region-specific gating. <h3>Key Findings</h3> Short-term plasticity in dopamine release is only weakly governed by Ca<sup>2+</sup> and initial release Short-term depression is strongly dependent on regulation of axonal excitability The DAT determines short-term plasticity and drives short-term depression DAT governs the balance between release-dependent and release-independent mechanisms
Reviews, Notes, and Listings: Diseases of the Vulva
Authors: David G. Mutch
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 March 1993Reviews, Notes, and Listings: Diseases of the VulvaDavid G. Mutch, MDDavid G. Mutch, MDWashington University School of Medicine, St. Louis, MO 63110.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-6-199303150-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Diseases of the VulvaJean F. Hewitt, Monique Pelisse, and Bernard Jean Paniel; eds. 212 pages. London: McGraw Hill Book Company; 1992. $145.00.A need exists in the literature for a practical text on vulvar diseases. The diagnosis of various vulvar diseases is usually made by visual inspection and subsequent biopsy. To be useful, a text on vulvar disease should have good descriptions of these diseases, followed by appropriate photographs. Few other current texts addressing the subject of vulvar disease have the appropriate visual aids to help the reader understand or get an impression of the spectrum of presentation of the various ... Author, Article, and Disclosure InformationAffiliations: Washington University School of Medicine, St. Louis, MO 63110. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 March 1993Volume 118, Issue 6Page: 477KeywordsBiopsyClinical laboratoriesEmbryologyLaboratory testsMalignant tumorsParasitic diseasesSigns and symptomsSystemic diseases ePublished: 15 August 2000 Issue Published: 15 March 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells
Authors: Ellen Weisberg, Johannes Roesel, Guido Bold, Pascal Furet, Jingrui Jiang, Jan Cools, Renee D. Wright, Erik Nelson, Rosemary Barrett, Arghya Ray, Daisy Moreno, Elizabeth Hall-Meyers, Richard Stone, Ilene Galinsky, Edward Fox, Gary Gilliland, John F. Daley, Suzan Lazo-Kallanian, Andrew L. Kung, James D. Griffin
Journal: Blood (2008)
Independent Prognostic Significance of Ischemic ST-Segment Response Limited to Recovery From Treadmill Exercise in Asymptomatic Subjects
Authors: Tomasz M. Rywik, Richard C. Zink, Neil S. Gittings, Akbar A. Khan, Jeanette G. Wright, Frances C. O’Connor, Jerome L. Fleg
Journal: Circulation (1998)

Although exercise-induced ST depression is an independent predictor of future coronary events in asymptomatic populations, the predictive value of ST depression beginning after exercise cessation is unknown.We analyzed the treadmill exercise tests of 825 healthy volunteers who were 22 to 89 years of age from the Baltimore Longitudinal Study of Aging. All subjects were free from coronary heart disease by history, physical examination, and resting ECG. From 825 participants, 611 (group 0) had no ischemic ST-segment changes during or after treadmill exercise, while 214 subjects developed > or = 1-mm flat or downsloping ST depression: 151 (group 1) had ST changes starting during exercise, and 63 (group 2) had changes limited to recovery. Groups 1 and 2 were similar in age, sex, smoking status, hypertension prevalence, fasting plasma glucose, and serum cholesterol (CHOL). However, both groups were older and had higher CHOL and prevalence of hypertension than group 0. Treadmill exercise duration, peak oxygen consumption, and maximal heart rate were similar between groups 1 and 2 but were lower than in group 0 (each P < 0.05). During a mean follow-up time of 9 years, 55 subjects developed coronary events (angina pectoris, myocardial infarction, or coronary death): 21 of 611 (3.4%) in group 0, 22 of 151 (14.6%) in group 1, and 12 of 63 (19%) in group 2 (P = 0.001). By survival analysis, the risk of coronary events was similar in groups 1 and 2 but significantly higher than in group 0 (P < 0.0001). Multiple logistic regression showed that age (odds ratio [OR] = 1.07 per year, P = 0.00001), CHOL (OR = 1.02 per 1 mg, P = 0.0001), and presence of ST-segment depression (OR = 2.59, P = 0.007 and OR = 2.38, P = 0.04 for groups 1 and 2, respectively) were independent predictors of events.Thus, ischemic ST-segment changes developing during recovery from treadmill exercise in apparently healthy individuals have adverse prognostic significance similar to those appearing during exercise.
Immunologic characterization of a recombinant American cockroach (<i>Periplaneta americana</i>) Per a 1 (Cr‐PII) allergen
Authors: NM Wang, MF Lee, CH Wu
Journal: Allergy (1999)

Background: Previously, we have identified several Per a 1 (Cr‐PII) allergens from a λgt22A cDNA library of Periplaneta americana . This study aimed to sequence clone C42 and determine its molecular and antigenic properties. Methods: The cDNA of C42 was sequenced and ligated into a bacteria expression vector, pET21. The recombinant proteins were purified by ion‐exchange and affinity chromatographies. Their antigenicities were analyzed by immunoblotting, ELISA, and binding inhibition with human IgE. Results: The nucleotide of the cDNA has been sequenced and the deduced amino acid which encodes a 446‐amino‐acid protein (50 kDa) determined. The recombinant C42 protein can bind both anti‐Per a 1 monoclonal antibodies and human IgE and showed a 54.4% (12/22) skin reactivity in atopic patients. Sequence homology searches revealed a high degree of identity to two other members of the Per a 1 family, C17 and C6, and the German cockroach ( Blattella germanica ) Bla g Bd90K allergen. Interestingly, these allergens all contain internal repeats, and the crude B. germanica extract, Per a 1, and recombinant allergens share similar antigenic determinant(s) as defined by ELISA and IgE‐binding inhibition studies. In IgE‐binding epitope studies, an immunopositive C42 fragment was first identified from partial protease digestion. Overlapping peptides were then generated by expression of restriction enzyme fragments in E. coli . The shortest peptide, C42‐P560, identified by monoclonal antibodies and human specific IgE, can inhibit IgE binding to C42. Conclusions: An additional Per a 1 allergen has been defined at the molecular level and characterized and preliminary results showed that a potential IgE‐reactive region is located within amino‐acid residue 358–446 of C42, which is an internal repeat. The results defined the boundaries of the antigenic site and will facilitate further epitope‐mapping studies.
Ireland leads the way for Europe in banning smoking in the workplace
Authors: M. Houston
Journal: BMJ (2003)

The planned ban on smoking in the workplace from next year has brought protests from Irish pubs and restaurants 

Who would have thought that Ireland—known for its myriad of pubs and hostelries—would become the first country in Europe to introduce a total ban on smoking in places of entertainment? But from 1 January next year a workplace ban on smoking will include all elements of the hospitality industry, from pubs and bars to restaurants, hotels, and even bed and breakfasts.

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Irish pubs, famed for their stout, will soon become smoke-free zones

Credit: www.josmenting.com

An estimated 7000 people die each year in Ireland from smoking related diseases. A recent national health and lifestyle survey showed a 4% decline in the number of people smoking, from 31% of the population in 1998 to 27% in 2002. The percentage of smokers fell in all age groups and social classes. However, the level of passive exposure to smoke in pubs and clubs remains high, affecting 47% of men and 32% of women.

The forthcoming ban continues Ireland's proactive record on tobacco control issues and is part of legislation aimed at providing comprehensive regulation and control of the sale, marketing, and distribution of tobacco products. It reflects about five years' work by non-governmental organisations, such as the Irish Cancer Society, as well …

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Change in HbA1c as a Measure of Quality of Diabetes Care
Authors: Nathaniel G. Clark, Gregory Pawlson
Journal: Diabetes Care (2006)

Data were included if the baseline A1C (collected the day of the consult or within 90 days prior) was Ն8.0%, and at least one subsequent A1C, performed after 3 months, was measured.A third A1C was collected in patients who had been seen for Ն6 months at the time of data collection.The mean Ϯ SD A1C was calculated for each of the three time points, and a t test was performed to determine statistical significance between levels.A total of 96 patients met the entry criteria.Of these, 54 (56%) had a third data point.The remainder had not yet been followed long enough at the time of data collection (n ϭ 32) or did not adhere to follow up (n ϭ 9).The mean A1C at entry was 10.36 Ϯ 1.66%.The mean first and second follow-up A1C levels were 8.06 Ϯ 1.68 and 7.68 Ϯ 1.38%, respectively.Changes from entry to first and second A1C were both statistically significant (P Ͻ 0.001).Seventy-four percent of patients at first follow-up A1C and 80% at the second demonstrated an A1C decline of Ն1%.In this brief observation, the majority of patients who were referred for endocrine consultation to evaluate and treat poor diabetes control showed clinically meaningful improvements in A1C.In evaluating quality of care, the DPRP looks at a cross section of randomly chosen patients.In a consultation practice, the diabetes specialist may accumulate many poorly controlled patients.Therefore, the impression is that quality of care is poor.Moreover, provider recognition may be less likely under the current scoring system.Yet, the DCCT demonstrated that reductions in microvascular complications, in particular retinopathy, can be seen with sustained A1C reductions even if the target of Ͻ7% is not achieved (5).Change in A1C may be a useful marker for quality of care given by diabetes consultants and can be used as an adjunct to the current DPRP standards, especially if longer-term data are used.
Recurrent Pulmonary Emboli with Duplication of the Inferior Vena Cava
Authors: Stephen W. Miller, Alan R. Baker, Thomas A. Raffin, Francis X. van Houten
Journal: New England Journal of Medicine (1975)

ALTHOUGH pulmonary emboli can originate in any part of the venous circulation, including the right side of the heart, the common sites for development of a thrombus are the deep veins of the lower extremities and the large pelvic veins. Surgical treatment of these patients by caval interruption may be markedly complicated by major venous anomalies of the cava, as demonstrated in the case reported below.Case ReportA 23-year-old mechanic had shortness of breath, cough and pleuritic pain in his chest. Similar complaints at ages 18 and 21 had been treated with anticoagulants. Physical examination revealed a blood pressure . . .
Duration of Rapamycin Treatment Has Differential Effects on Metabolism in Mice
Authors: Yimin Fang, Reyhan Westbrook, Cristal Hill, Ravneet K. Boparai, Oge Arum, Adam Spong, Feiya Wang, Martin A. Javors, Jie Chen, Liou Y. Sun, Andrzej Bartke
Journal: Cell Metabolism (2013)

The evolutionarily conserved target of rapamycin (TOR) signaling controls growth, metabolism, and aging. In the first robust demonstration of pharmacologically-induced life extension in mammals, longevity was extended in mice treated with rapamycin, an inhibitor of mechanistic TOR (mTOR). However, detrimental metabolic effects of rapamycin treatment were also reported, presenting a paradox of improved survival despite metabolic impairment. How rapamycin extended lifespan in mice with such paradoxical effects was unclear. Here we show that detrimental effects of rapamycin treatment were only observed during the early stages of treatment. These effects were reversed or diminished in mice treated for 20 weeks, with better metabolic profiles, increased oxygen consumption and ketogenesis, and markedly enhanced insulin sensitivity. Thus, prolonged rapamycin treatment lead to beneficial metabolic alterations, consistent with life extension previously observed. Our findings provide a likely explanation of the "rapamycin paradox" and support the potential causal importance of these metabolic alterations in longevity.
Endoscopic Removal of Foreign Bodies Using a Newly Developed Extractor
Authors: A. E. Hennig, K. Seuberth
Journal: Endoscopy (1988)

A newly developed extractor for the endoscopic removal of foreign bodies has already been used with success. It can be rotated through 360 degrees, so that foreign bodies can be grasped from any angle. Capture and extraction of the foreign body is accomplished with a band-like snare, the inside surface of which is provided with tiny "studs". With the aid of this extractor, foreign bodies can be captured and removed quickly, reliably, and without risk to the patient.
Engraftment of retroviral EGFP-transduced bone marrow in mice prevents rejection of EGFP-transgenic skin grafts
Authors: Goran Andersson, Maria Denaro, Kevin Johnson, Peter Morgan, Angela Sullivan, Stuart Houser, Clive Patience, Mary E White-Scharf, Julian D Down
Journal: Molecular Therapy (2003)

We have investigated whether a state of tolerance toward EGFP-expressing skin tissue can be induced by prior establishment of EGFP molecular chimerism by transplant of gene-transduced bone marrow in mice. Irradiated (10 Gy) C57BL/6J mice were transplanted with bone marrow cells transduced with two different retroviral vectors encoding EGFP. EGFP-transduced, mock-transduced, and age-matched control mice received skin grafts from both C57BL/6 EGFP-transgenic (B6-EGFP. Tg) and MHC-mismatched B10.A donor mice at 8, 29, or 39 weeks after bone marrow transplantation. Although 14 of 17 control mice rejected EGFP.Tg skin grafts within 100 days, 24 of 25 mice receiving EGFP-expressing bone marrow cells accepted their B6-EGFP.Tg grafts out to 200 days after skin grafting, including animals with undetectable levels of EGFP expression in blood cells. The EGFP-transduced animals rejected third-party grafts from MHC-mismatched mice within 20 days, indicating that acceptance of the EGFP-expressing skin grafts was the result of the induction of specific and operational immune tolerance. Thus, our data indicate that (a) EGFP-expressing tissue elicits an immunological rejection in C57BL/6 mice and (b) tolerance can be induced by engrafting relatively small numbers of EGFP-transduced hematopoietic cells. These experiments utilizing EGFP as an immunogen point to the wider therapeutic potential of employing transplantation of gene-transduced hematopoietic cells for establishing immunological tolerance and thereby preventing rejection of gene-corrected cells and tissues.