tbuckley/cabot-search huggingface dataset:
Disruption of Transforming Growth Factor β Signaling by a Novel Ligand-dependent Mechanism
Authors: Tania Fernandez, Stephanie Amoroso, Shellyann Sharpe, Gary M. Jones, Valery Bliskovski, Alexander Kovalchuk, Lalage M. Wakefield, Seong-Jin Kim, Michael Potter, John J. Letterio
Journal: The Journal of Experimental Medicine (2002)

Transforming growth factor (TGF)-β is the prototype in a family of secreted proteins that act in autocrine and paracrine pathways to regulate cell development and function. Normal cells typically coexpress TGF-β receptors and one or more isoforms of TGF-β, thus the synthesis and secretion of TGF-β as an inactive latent complex is considered an essential step in regula-ting the activity of this pathway. To determine whether intracellular activation of TGF-β results in TGF-β ligand–receptor interactions within the cell, we studied pristane-induced plasma cell tumors (PCTs). We now demonstrate that active TGF-β1 in the PCT binds to intracellular TGF-β type II receptor (TβRII). Disruption of the expression of TGF-β1 by antisense TGF-β1 mRNA restores localization of TβRII at the PCT cell surface, indicating a ligand-induced impediment in receptor trafficking. We also show that retroviral expression of a truncated, dominant-negative TβRII (dnTβRII) effectively competes for intracellular binding of active ligand in the PCT and restores cell surface expression of the endogenous TβRII. Analysis of TGF-β receptor–activated Smad2 suggests the intracellular ligand–receptor complex is not capable of signaling. These data are the first to demonstrate the formation of an intracellular TGF-β–receptor complex, and define a novel mechanism for modulating the TGF-β signaling pathway.
Point-of-Care Measurements of HbA1c: Simplicity Does Not Mean Laxity With Controls
Authors: Viviane Leca, Zouher Ibrahim, Elise Lombard-Pontou, Marie Maraninchi, Régis Guieu, Henri Portugal, René Valéro, Bernard Vialettes
Journal: Diabetes Care (2012)

Point-of-care HbA1c measurements (POC-A1Cs) have been adopted by many diabetes clinics to improve the quality of care provided to their patients (1). Herein, we show that reliability of this approach might be questioned. POC-A1Cs routinely used in the ambulatory section of our diabetes clinic was evaluated on 100 diabetic patients (type 1, n = 58; type 2, n = 42) attending the clinic from 1 October 2011 to 30 November 2011. Patients with abnormal hemoglobin traits or shortened erythrocyte life span were excluded. Blood-capillary samples were analyzed by POC-A1C (DCA Vantage; Siemens Medical Solutions Diagnostics, Cergy-Pontoise, France) and venous EDTA-anticoagulated blood specimens by the central laboratory high-performance liquid chromatography measurement (Tosoh HLC-723 GHb G8; BioSciences, Lyon, France). Both methods were certified (NGSP/Diabetes Control and Complications Trial [DCCT] and International Federation of Clinical …
Long-Term Outcome after En Bloc Resection of Non–Small-Cell Lung Cancer Invading the Pulmonary Sulcus and Spine
Authors: Stéphane Collaud, Thomas K. Waddell, Kazuhiro Yasufuku, Andrew F. Pierre, Gail E. Darling, Marcelo Cypel, Yoga R. Rampersaud, Stephen J. Lewis, Frances A. Shepherd, Natasha B. Leighl, John Cho, Andrea Bezjak, Ming Sound Tsao, Shaf Keshavjee, Marc de Perrot
Journal: Journal of Thoracic Oncology (2013)
Review: ACE-Is or ARBs reduce adverse CV outcomes regardless of baseline systolic blood pressure
Authors: Vibhuti Singh
Journal: Annals of Internal Medicine (2012)

Source Citation McAlister FA; Renin Angiotensin System Modulator Meta-Analysis Investigators. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta-analysis of randomized trials. Eur Heart J. 2012;33:505-14. 22041554
Health economics of asthma: assessing the value of asthma interventions
Authors: J. D. Campbell, D. E. Spackman, S. D. Sullivan
Journal: Allergy (2008)

The aim of this systematic review was to summarize and assess the quality of asthma intervention health economic studies from 2002 to 2007, compare the study findings with clinical management guidelines, and suggest avenues for future improvement of asthma health economic studies. Forty of the 177 studies met our inclusion criteria. We assessed the quality of studies using The Quality of Health Economic Studies validated instrument (total score range: 0–100). Six studies (15%) had quality category 2, 26 studies (65%) achieved quality category 3, and the remaining eight (20%) studies were scored as the highest quality level, category 4. Overall, the findings from this review are in line with the Global Initiative for Asthma clinical guidelines. Many asthma health economic studies lacked appropriate long term time horizons to match the chronic nature of the disease and suffered from using effectiveness measures that did not capture all disease related risks and benefits. We recommend that new asthma simulation models: be flexible to allow for long term time horizons, focus on using levels of asthma control in their structure, and estimate both long term asthma specific outcomes like well‐controlled time as well as generic outcomes such as quality adjusted survival.
Modern Perspectives in Adolescent Psychiatry
Authors: Barry Liskow
Journal: JAMA (1972)

Judging by this book, adolescent psychiatry appears to be experiencing an identity crisis. The 20 authors contributing to this volume, while they demonstrate the diversity of adolescent psychiatry, also indicate this field's current difficulty both in defining itself and in separating itself from adult and child psychiatry. The book is divided into two major sections. The first, mislabeled as "Scientific," mainly contains arguments for or against Erik Erickson's theories regarding adolescence, arguments which, with few exceptions, are based on anecdotal evidence and armchair speculation. Only three chapters in this section seem able to avoid mention of Erickson—one on sexuality in adolescence, based on a British study of questionable current relevance; one on the physiology of adolescence and one on intelligence ratings in adolescence, both competently written but neither making any substantial effort to relate itself to adolescent psychiatry. The second section, labeled as "Clinical," extends from a chapter on depersonalization
Functions of the Lower-Class Partial Family
Authors: PAUL L. ADAMS
Journal: American Journal of Psychiatry (1973)

Six million children in the United States experience the partial (fatherless) family. This type of family, which appears frequently in lower-class areas, somehow functions as a viable form. It is not a congenial structure for understanding by means of the classic psychoanalytic model or other "deficit" models. A "difference" model is proposed for understanding the lower-class partial family's functions regarding sexuality, economic life chances, authority, and honor. It is poverty combined with fatherlessness that accounts for the differences and, perhaps, the deficits.
Malalignment of the shoulder after stroke.
Authors: R G Smith, J G Cruikshank, S Dunbar, A J Akhtar
Journal: BMJ (1982)

One hundred and ten consecutive patients (51 men, 59 women) admitted to a stroke unit were studied for radiographic changes at the shoulder on the affected side. Malalignment was found in 51 (46%) patients, of whom 37 (72.5%) had changes on the initial x-ray film and a further 14 (27.5) developed malalignment over the following 12 months. These findings indicate that malalignment of the shoulder is common in the early stages of a stroke and may be missed unless radiographs are taken with the patient erect and the arm unsupported. Malalignment may lead to delay and limitation in restoration of function. The consequences of malalignment can be prevented by correct handling, positioning, and full passive movement of the shoulder from the onset of the stroke.
Abstract 4459: Apricoxib upregulates 15-PGDH and PGT in HNSCC
Authors: Maie St. John, Guanyu Wang, Jie Luo, Qahera Munaim, Jay M. Lee, Francis Burrows, Sara Zaknoen, Steven M. Dubinett
Journal: Cancer Research (2010)

Abstract Head and neck squamous cell carcinoma (HNSCC), is the sixth most common cancer in the world. Patients with HNSCC are at considerable risk of mortality, with more than 300,000 deaths attributable to the disease per year. The five-year survival rate for patients with advanced head and neck cancer remains approximately 15-20 percent, emphasizing the importance of new therapeutic strategies. In spite of extensive research on EGFR and COX-2 inhibitors, their combined use for HNSCC is still in its developmental stage. We evaluated the efficacy of the newer COX-2 inhibitor, apricoxib, in HNSCC cell lines. Here, we report that in comparison with celecoxib, apricoxib shows greater efficacy in vitro; and we define the mechanisms which may be responsible for this. Our studies show that apricoxib is effective in preventing tumor cell growth in 3-dimensional, and anchorage-independent growth assays; as well as decreasing the capacity for tumor cell migration. Treatment of HNSCC cells with apricoxib also causes greater up regulation of E-cadherin expression and down regulation of vimentin, as compared with celecoxib treatment. This has significant implications for targeted chemoprevention and anti-cancer therapy because E-cadherin expression has been implicated as a marker of sensitivity to EGFR TKI. In addition to PGE2 down regulation, indicating COX-2 inhibition, we also show that apricoxib treatment causes a marked up regulation of 15-PGDH (prostaglandin dehydrogenase) and PGT (prostaglandin transporter), both of which decrease PGE2. These effects are further amplified in 3-dimensional culture, indicating the import of the microenvironment in drug efficacy. This up regulation of 15-PGDH and PGT with apricoxib treatment may explain its increased efficacy over celecoxib in the assays we tested. As apricoxib affects other pathways of PGE2 degradation and uptake, there is ultimately less PGE2 to drive metastasis and tumor progression. These newly defined mechanisms for the increased efficacy of apricoxib have important implications for targeted chemoprevention and therapy. 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 4459.
Factitious Illness v Conversion Disorder
Authors: Laurens D. Young
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The three cases of respiratory distress associated with wheezing heard loudest over the larynx and normal pulmonary function certainly point out the value of a careful physical examination and sensitivity to the patient's emotional history to avoid unnecessary treatment for asthma (1982;248:2878). However, factitious illness was not the best diagnosis in at least two of the cases (2 and 3) and probably a third (case 1). Conversion disorder, with or without a concurrent anxiety disorder, would be much more likely and helpful to consider in these cases. Conversion disorder involves a loss or alteration of physical function, often in the voluntary nervous system. The change in function is thought to be associated with channeling of anxiety about psychological conflicts into somatic outlets, which is not explained by known physiological disease and in which a temporal connection is found between the onset of physical symptoms, psychological disturbance, and
A Surgical Artist at War: the Paintings and Sketches of Sir Charles Bell 1809–1815
Authors: Martin R Howard
Journal: Journal of the Royal Society of Medicine (2005)

Born into a respectable Scottish family in 1774, Charles Bell was an accomplished anatomist, surgeon, physiologist, author and artist. His highly successful civil medical career coincided with the Revolutionary and Napoleonic Wars of 1792–1815. In early 1809, Sir John Moore’s Peninsular Army landed on the South Coast following the desperate retreat to Corunna. About 28 000 ill and wounded soldiers disembarked, causing consternation in the local population. The army medical services were overwhelmed and Bell was among a number of civilian surgeons who volunteered to help. He performed a similar altruistic service 6 years later in the aftermath of the Battle of Waterloo where 55 000 dead and wounded were left on the field. These sudden transitions from civilian to military surgery were not straightforward and Bell’s operation results in the Brussels hospitals were not impressive. Only one of his 12 amputation cases survived—a mortality rate of 92% which was high even allowing for the more hazardous nature of secondary operations which had had to be delayed long after the initial injury.
Evidence for Humoral Factors in Renoprival Hypertension
Authors: PAUL A. RONDELL, RUTH B. MCVAUGH, DAVID F. BOHR
Journal: Circulation (1958)

Plasma of renoprival hypertensive rats was found to have an exaggerated constrictor effect on isolated rat aorta strips, however, no pressor effect was produced in acutely nephrectomized rats cross-circulated with renoprival hypertensive animals. It is suggested that if the constrictor element of the plasma from renoprival hypertensive rats is not just an artifact of the aorta strip assay technic but does exist and play a role in renoprival hypertension, it does so by acting on arterioles sensitized by the chronic a-renal condition.
Prospective Evaluation of an Extended 21-Core Biopsy Scheme as Initial Prostate Cancer Diagnostic Strategy
Authors: Guillaume Ploussard, Nathalie Nicolaiew, Charles Marchand, Stéphane Terry, Francis Vacherot, Dimitri Vordos, Yves Allory, Claude-Clément Abbou, Laurent Salomon, Alexandre de la Taille
Journal: European Urology (2012)
The Croonian Lecture on Preventive Inoculation
Authors: M. Roux
Journal: BMJ (1889)

In troduction.-JennerianVaccination.-'I'heDiscovery of the Arti- ficial Attenuation of TVirus.-Pasteur'sResearches on Ferments.-Researches on Chicken Cholera.-AttenuatingInfluence of the Air.-Anthrax.Virus: its Attenuation or IntensiJication.-PreventiveInoculationfor Rabies
Clinical Laboratory Methods
Authors: Frances K. Widmann
Journal: JAMA (1975)

<b>Laboratory Medicine: Clinical Microscopy,</b>by James A. Freeman and Myrton F. Beeler, 395 pp, 160 illus, $16.50, Philadelphia, Lea &amp; Febiger, 1974. Here are two good, new, old-fashioned books. Well-organized, comprehensive chapters feature manual methods, step-by-step directions, and individual paragraphs about clinical interpretations. The eighth edition of what began, in 1936, as Bray's<i>Synopsis of Clinical Laboratory Method</i>includes innumerable procedures new since Bray's day—many new since the previous edition in 1968—but the audience is still the same careful, imaginative bench worker. New this year is a manual covering the catch-all realm called clinical microscopy—that often malodorous niche of the laboratory where tests are done on excreta—but the approach is similar to that of the older books. The Bauer, Ackerman, Torro manual does as good a job as possible in trying to put all known knowledge between two covers. In 834 text pages there are nods to histologic technique, virus
Relationship Between Habitual Physical Activity and Insulin Area Among Individuals With Impaired Glucose Tolerance: The San Luis Valley Diabetes Study
Authors: Judith G Regensteiner, Susan M Shetterly, Elizabeth J Mayer, Robert H Eckel, William L Haskell, Judith Baxter, Richard F Hamman
Journal: Diabetes Care (1995)

OBJECTIVE To determine whether higher levels of physical activity are associated with lower fasting insulin levels and lower insulin areas under the oral glucose tolerance curve in individuals with impaired glucose tolerance (IGT) in a community setting. RESEARCH DESIGN AND METHODS Data from a cross-sectional study of a population consisting of 219 Hispanic and non-Hispanic white men and women with IGT (by World Health Organization criteria) in two rural Colorado counties were analyzed. Total physical activity was assessed by a 7-day physical activity recall, from which metabolic equivalents (METs) were estimated (expressed as MET h/week). Relationships of MET h/week with fasting insulin levels and insulin areas were assessed while considering obesity, age, and other risk factors known to influence fasting insulin level and insulin area. RESULTS Among all subjects, univariate analyses showed that higher physical activity levels were associated with lower mean insulin areas and fasting insulin levels (both P ≤ 0.05). Multiple linear regression showed that higher levels of physical activity were significantly associated with lower values of of the insulin area (P &amp;lt; 0.001) but not with fasting insulin levels. The relationship between insulin area and habitual physical activity was independent of obesity, fat distribution, and age. CONCLUSIONS On the basis of cross-sectional data, we conclude that higher levels of habitual physical activity are associated with lower insulin areas in a population of individuals with IGT. Understanding the impact of physical activity on markers of insulin action in individuals with IGT is important because of the greatly enhanced risk of non-insulin-dependent diabetes mellitus and, hence, cardiovascular disease in this population.
P570 ANALYSIS OF THE ADHERENCE TO A HEPATOCELLULAR CARCINOMA (HCC) SURVEILLANCE PROGAMME BASED ON BIANNUAL CONTROLS
Authors: M.L. González-Diéguez, A. Mancebo, V. Cadahía, R. Pérez, M. Varela, C. Navascues, M. Rodríguez
Journal: Journal of Hepatology (2014)
753 NUCLEOS(T)IDE ANALOGUES CAN BE SAFELY DISCONTINUED IN CHRONIC HEPATITIS B PATIENTS ACHIEVING HBSAG SEROCLEARANCE
Authors: E. Vezali, P. Lampertico, F. Invernizzi, M. Iavarone, M. Viganò, F. Facchetti, G. Lunghi, M. Colombo
Journal: Journal of Hepatology (2011)
Abstract A54: CnABP, a novel modulator of the Calcineurin-NFAT signaling pathway, is overexpressed in Wilms' tumors and promotes cell migration
Authors: Alana H.T. Nguyen, Melanie Beland, Yaned Gaitan, Maxime Bouchard
Journal: Cancer Research (2009)

Abstract Wilms' tumor (WT) is a classical cancer type that arises from abnormal differentiation of kidney progenitor cells, and occurs at a frequency of 1 in 10,000 live births, accounting for approx. 90% of childhood kidney cancer. Abnormally high levels of Pax2 (paired-box protein 2), a key regulator of kidney development, have been observed in both WT and renal cell carcinoma, which correlate with proliferation and increased invasiveness. Therefore the misexpression of Pax2 and its target genes may play an important role in tumor initiation and/or progression. To test this, we screened for target genes of Pax2 by cDNA microarray in the embryonic kidney. We identified CnABP (Calcineurin A Binding Protein), a novel gene under Pax2 regulation. In situ hybridization indicates that CnABP coexpresses with Pax2 in the condensing mesenchyme, the abnormal differentiation of which gives rise to WT. Furthermore, expression analysis by quantitative PCR indicates that CnABP is overexpressed in more than 70% of Wilms' tumors. Interestingly, in the proportion of tumors with upregulated PAX2 expression, more than 80% also overexpress CnABP. We characterized CnABP as a membrane-anchored protein that primarily promotes cell proliferation and migration. Mediators of these activities were investigated by Yeast-two-hybrid and immunoprecipitation, which identified an interaction between CnABP and Calcineurin A, the catalytic subunit of a calcium-responsive serine/threonine phosphatase Calcineurin. We showed that CnABP modulates phosphatase activities of Calcineurin, which consequently inhibits calcium/Calcineurin-dependent NFAT nuclear translocation. We further demonstrated that the inhibition of NFAT nuclear localization results in reduced NFAT-specific transcriptional activity. Components of the Calcineurin complex have been reported as differentially expressed genes distinguishing recurrent from non-recurrent Wilms' tumors. This is in line with the evidence we presented, as CnABP is upregulated in Wilms' tumors and is shown to promote proliferation and migration. Citation Information: Cancer Res 2009;69(23 Suppl):A54.
Scientists mistakenly study bovine instead of sheep tissue
Authors: Mark Gould
Journal: BMJ (2001)

A five year project to detect the presence of bovine spongiform encephalopathy (BSE) in sheep could have been ruined by a labelling error in the laboratory, which meant researchers mistakenly experimented with cow brain tissue instead.

The Department for Environment, Food and Rural Affairs has ordered an independent audit of the £217 000 ($325 500) project, which was carried out by the Edinburgh based Institute for Animal Health. Results should be known within two weeks. It has also ordered an audit into the government's Veterinary Laboratories …
Use of a Potent, Long Acting Agonist of Gonadotropin-Releasing Hormone in the Treatment of Precocious Puberty*
Authors: PAUL A. BOEPPLE, M. JOAN MANSFIELD, MARGARET E. WIERMAN, CRAIG R. RUDLIN, HANS H. BODE, JOHN F. CRIGLER, JOHN D. CRAWFORD, WILLIAM F. CROWLEY
Journal: Endocrine Reviews (1986)

STUDIES UTILIZING the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects.
Science commentary: Why wine might be less harmful than beer and spirits
Authors: A. Berger
Journal: BMJ (1998)

Alcoholic drinks are well known to have carcinogenic properties, and several possible mechanisms have been postulated to explain this. In general terms ethyl alcohol slows down protein synthesis. One obvious consequence of this is that cell repair mechanisms will be inhibited, which could lead to malignant changes. A synergy between alcohol and smoking is also well documented: heavy smokers who also drink heavily are many times more likely to develop oesophageal cancer than non-smokers who drink. In …