tbuckley/cabot-search huggingface dataset:
TAUNTON AND SOMERSET HOSPITAL. CASE OF ANEURISM OF THE COMMON FEMORAL ARTERY TREATED SUCCESSFULLY BY COMPRESSION: WITH REMARKS
Authors: A. Prichard
Journal: BMJ (1856)

white spots in the centre, exactly corresponding with those described in the lung of J. G.Such a state is not rare, but I have never before observed it so intense.If I have not alredy too far trespassed upon your space, I will add a few particulars of a case of malposition of the heart.L. W., aged 22, was admitted an out-patient in October.She complained; of much palpitation and shortness of breath.Is a tall girl, with dark hair and eyes, sallow; changes colour often, and is very subject to throbbing headache and giddiness, with pain in the eyes.Catamenia regular; never swells in abdomen or limbs; sleeps well, but starts and dreams much.On examination, I found the chest slightly bulged on the right side.The heart's im pulse isible under the second, third, fourth, and fifth ribs, on the right side of the sternum.There was a loud bruit
Predicting outcome in severe ulcerative colitis.
Authors: S P Travis, J M Farrant, C Ricketts, D J Nolan, N M Mortensen, M G Kettlewell, D P Jewell
Journal: Gut (1996)

Simple criteria are needed to predict which patients with severe ulcerative colitis will respond poorly to intensive medical treatment and require colectomy.To find out if the early pattern of change in inflammatory markers or other variables could predict the need for surgery and to evaluate the outcome of medical treatment during one year follow up.51 consecutive episodes of severe colitis (Truelove and Witts criteria) affecting 49 patients admitted to John Radcliffe Hospital, Oxford.Prospective study monitoring 36 clinical, laboratory, and radiographic variables. All episodes treated with intravenous and rectal hydrocortisone and 14 of 51 with cyclosporine.Complete response in 21 episodes (< or = 3 stools on day 7, without visible blood), incomplete response in 15 (> 3 stools or visible blood on day 7, but no colectomy), and colectomy on that admission in 15. During the first five days, stool frequency and C reactive protein (CRP) distinguished between outcomes (p < 0.00625, corrected for multiple comparisons) irrespective of whether patients or the number of episodes were analysed. It could be predicted on day 3, that 85% of patients with more than eight stools on that day, or a stool frequency between three and eight together with a CRP > 45 mg/l, would require colectomy. For patients given cyclosporine, four of 14 avoided colectomy but two continued to have symptoms. After admission, complete responders remained in remission for a median nine months and had a 5% chance of colectomy. Incomplete responders had a 60% chance of continuous symptoms and 40% chance of colectomy.After three days intensive treatment, patients with frequent stools (> 8/day), or raised CRP (> 45 mg/l) need to be identified, as most will require colectomy on that admission. The role of cyclosporine for treating severe colitis has yet to be defined. After seven days' treatment, patients with > 3 stools/day of visible blood have a 60% chance of continuous symptoms and 40% chance of colectomy in the following months.
Respiratory work disability and occupational outcomes in adults with asthma and bronchial hyperresponsiveness
Authors: Nicola Murgia, Giulia Paolocci, Angela Gambelunghe, Marco dell'Omo, Ilenia Folletti, Giacomo Muzi, Giuseppe Abbritti
Journal: European Respiratory Journal (2011)

Background:  The correlation between asthma and work disability has been demonstrated in previous surveys. Changing job for respiratory problems often defines respiratory work disability. Little is known about occupations of asthmatics with respiratory work disability after they were forced to change job. This study investigates factors associated to respiratory work disability in asthmatics, focusing on occupational outcomes.   Methods:  342 adults in working age with asthma, diagnosed by GINA criteria and methacoline challenge or bronchodilator response, answered to a questionnaire. Subjects with occupational asthma were excluded. Respiratory work disability was defined as to have changed job/task because of asthma. Information about pulmonary function tests and skin prick tests were obtained from medical records.   Results:  22 subjects reported respiratory work disability. Age, sex, smoking, atopy, were not risk factors for changing work. Patients with work disability referred more often uncontrolled asthma (72.7% vs 60.5%), regular use of asthma controllers (81.1% vs 66.6%) and asthma relievers, even if these differences were not significant. Workers that have changed job because of asthma were still prone to work exacerbated asthma in the last year (81.8% vs 35.3%; OR 5.75, CI 95% 1.77-18.71) and work exacerbated rhinitis in the last year (61.9% vs 31.6%; OR 2.90, CI 95% 1.07-7.02), remaining exposed to known asthmogens (63.6% vs 54.1%).   Conclusions:  In this study atopy did not predict job change. Maybe because the current economical situation, workers with respiratory work disability did not move to more safe occupations, remaining at risk of work exacerbated asthma.
Gastric colonisation with a restricted commensal microbiota replicates the promotion of neoplastic lesions by diverse intestinal microbiota in the<i>Helicobacter pylori</i>INS-GAS mouse model of gastric carcinogenesis
Authors: Kvin Lertpiriyapong, Mark T Whary, Sureshkumar Muthupalani, Jennifer L Lofgren, Eric R Gamazon, Yan Feng, Zhongming Ge, Timothy C Wang, James G Fox
Journal: Gut (2013)

<h3>Objectives</h3> Gastric colonisation with intestinal flora (IF) has been shown to promote <i>Helicobacter pylori</i> (<i>Hp</i>)-associated gastric cancer. However, it is unknown if the mechanism involves colonisation with specific or diverse microbiota secondary to gastric atrophy. <h3>Design</h3> Gastric colonisation with Altered Schaedler9s flora (ASF) and <i>Hp</i> were correlated with pathology, immune responses and mRNA expression for proinflammatory and cancer-related genes in germ-free (GF), <i>Hp</i> monoassociated (m<i>Hp</i>), restricted ASF (rASF; 3 species), and specific pathogen-free (complex IF), hypergastrinemic INS-GAS mice 7 months postinfection. <h3>Results</h3> Male mice cocolonised with rASF<i>Hp</i> or IF<i>Hp</i> developed the most severe pathology. IF<i>Hp</i> males had the highest inflammatory responses, and 40% developed invasive gastrointestinal intraepithelial neoplasia (GIN). Notably, rASF<i>Hp</i> colonisation was highest in males and 23% developed invasive GIN with elevated expression of inflammatory biomarkers. Lesions were less severe in females and none developed GIN. Gastritis in male rASF<i>Hp</i> mice was accompanied by decreased <i>Clostridum species</i> ASF356 and <i>Bacteroides species</i> ASF519 colonisation and an overgrowth of <i>Lactobacillus murinus</i> ASF361, supporting that inflammation-driven atrophy alters the gastric niche for GI commensals. <i>Hp</i> colonisation also elevated expression of <i>IL-11</i> and cancer-related genes, <i>Ptger4</i> and <i>Tgf-β</i>, further supporting that <i>Hp</i> infection accelerates gastric cancer development in INS-GAS mice. <h3>Conclusions</h3> rASF<i>Hp</i> colonisation was sufficient for GIN development in males, and lower GIN incidence in females was associated with lower inflammatory responses and gastric commensal and <i>Hp</i> colonisation. Colonisation efficiency of commensals appears more important than microbial diversity and lessens the probability that specific gastrointestinal pathogens are contributing to cancer risk.
Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma
Authors: Raffi Tachdjian, Clinton Mathias, Shadi Al Khatib, Paul J. Bryce, Hong S. Kim, Frank Blaeser, Brian D. O'Connor, Danuta Rzymkiewicz, Andrew Chen, Michael J. Holtzman, Gurjit K. Hershey, Holger Garn, Hani Harb, Harald Renz, Hans C. Oettgen, Talal A. Chatila
Journal: The Journal of Experimental Medicine (2009)

Polymorphisms in the interleukin-4 receptor α chain (IL-4Rα) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4Rα has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target– and tissue-specific manner to mediate heightened expression of a subset of IL-4– and IL-13–responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4Rα–dependent signaling.
Redefining Health Care: Creating Value-Based Competition on Results
Authors: J A Muir Gray
Journal: BMJ (2006)

T his book “grew out of a puzzle: why is competition failing in health care?” This first sentence of the book is followed by a rationale, namely that “throughout the economy competition among private sector rivals is the most powerful force yet discovered for driving improvements in the quality and cost of products and services”—except in health care in the United States. The authors, who have studied competition in many industries, set out their hypothesis in this readable book. The book is an example of excellent value: at the time of writing the hardback, with its 506 pages of high quality paper, could be bought on http://www.amazon.com/ for only $23.10 (about £12).

Michael E Porter, Elizabeth Olmsted Teisberg

Harvard Business School Press, $35, pp 528 ISBN 1 59139 7782 …
Common Variants in UMOD Associate with Urinary Uromodulin Levels
Authors: Matthias Olden, Tanguy Corre, Caroline Hayward, Daniela Toniolo, Sheila Ulivi, Paolo Gasparini, Giorgio Pistis, Shih-Jen Hwang, Sven Bergmann, Harry Campbell, Massimiliano Cocca, Ilaria Gandin, Giorgia Girotto, Bob Glaudemans, Nicholas D. Hastie, Johannes Loffing, Ozren Polasek, Luca Rampoldi, Igor Rudan, Cinzia Sala, Michela Traglia, Peter Vollenweider, Dragana Vuckovic, Sonia Youhanna, Julien Weber, Alan F. Wright, Zoltán Kutalik, Murielle Bochud, Caroline S. Fox, Olivier Devuyst
Journal: Journal of the American Society of Nephrology (2014)

Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown. We conducted a meta-analysis of urinary uromodulin levels to identify associated common genetic variants in the general population. We included 10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model. We also tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P<0.001). In all cohorts, carriers of a G allele of this variant had higher uromodulin levels than noncarriers did (geometric means 10.24, 14.05, and 17.67 μg/g creatinine for zero, one, or two copies of the G allele). rs12446492 in the adjacent gene PDILT (protein disulfide isomerase-like, testis expressed) also reached genome-wide significance (P<0.001). Regarding genes expressed in the thick ascending limb, variants in KCNJ1, SORL1, and CAB39 associated with urinary uromodulin levels. These data indicate that common variants in the UMOD promoter region may influence urinary uromodulin levels. They also provide insights into uromodulin biology and the association of UMOD variants with renal function.
180‐kDa bullous pemphigoid antigen defective generalized atrophic benign epidermolysis bullosa: report of four cases with an unusually mild phenotype
Authors: None Mazzanti, None Gobello, None Posteraro, None Paradisi, None Meneguzzi, None Chinni, None Zambruno
Journal: British Journal of Dermatology (1998)

Generalized atrophic benign epidermolysis bullosa (GABEB) is a rare variant of non-lethal junctional epidermolysis bullosa characterized by generalized skin blistering healing with atrophy and by atrophic alopecia with onset in childhood. Other features include mild mucosal blistering, dental abnormalities and nail dystrophy. We report four additional cases of GABEB from two families originating from the same isolated village. The patients shared an unusually mild clinical phenotype with cutaneous blisters strictly limited to trauma sites and rare occurrence of oral mucosal lesions. Scalp, eyelash and eyebrow alopecia was present in only two cases. Immunofluorescence studies showed a markedly reduced expression of the 180-kDa bullous pemphigoid antigen (BP180), and northern analysis of cultured keratinocytes indicated that the gene encoding for BP180 is affected in these GABEB patients.
Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors.
Authors: K L Rock, B Benacerraf, A K Abbas
Journal: The Journal of Experimental Medicine (1984)

The present study examines the ability of hapten-specific murine splenic B lymphocytes to present hapten-proteins to carrier-specific T cell hybridomas. BALB/cB cells specific for 2,4,6-trinitrophenyl (TNP) were isolated from spleens of immune mice by elution from TNP-gelatin-coated dishes. Such cells presented the TNP-modified terpolymer, GL phi, at concentrations as low as 0.1 microgram/ml, to a GL phi-specific, I-Ed-restricted, interleukin 2-producing T cell hybridoma. In contrast, the same B lymphocytes required 1,000-fold higher concentrations of unmodified GL phi to stimulate the same T cell hybridoma. The presentation of low concentrations of TNP-GL phi by TNP-specific B lymphocytes was significantly or completely blocked by anti-Ig antibody or TNP-proteins, indicating that surface Ig receptors were critically involved in this phenomenon. Finally, binding of TNP-proteins did not alter the ability of the B cells to present unrelated, unhaptenated proteins or to stimulate alloreactive T cells. These results suggest that surface Ig receptors serve to focus antigens onto specific B lymphocytes and that such cells are highly efficient at presenting linked antigenic determinants to T cells. The implications of these findings for the mechanisms of physiologic, histocompatibility-restricted T-B collaboration are discussed.
936-87 Serial Dobutamine Stress Echocardiography for Detection of Cardiac Allograft Vasculopathy
Authors: Christoph H. Spes, Harald Mudra, Susanne D. Schnaack, Johannes Rieber, Florian Reichle, Thomas M. Krüger, Volker Klauss, Peter Überfuhr, Bruno Meiser, Christiane E. Angermann, Karl Theisen
Journal: Journal of the American College of Cardiology (1995)
Cost effectiveness of human papillomavirus test of cure after treatment for cervical intraepithelial neoplasia in England: economic analysis from NHS Sentinel Sites Study
Authors: R. Legood, M. Smith, J.-B. Lew, R. Walker, S. Moss, H. Kitchener, J. Patnick, K. Canfell
Journal: BMJ (2012)

<b>Objectives</b> To evaluate the cost effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia (CIN). <b>Design</b> Economic analysis using a Markov modelling approach to combine cost and epidemiological data from the NHS Sentinel Sites Study with data from previous studies of post-treatment recurrence rates. <b>Setting</b> English NHS Cervical Cancer Screening Programme. <b>Interventions</b> Management guidelines after treatment of CIN involving annual cytology follow-up for 10 years, compared with alternative protocols using the human papillomavirus test to reduce the amount of post-treatment surveillance. <b>Main outcome measures</b> Cases of underlying CIN3+ averted at 10 years and costs per 1000 women treated. <b>Results</b> Model predictions indicated that, at observed levels of compliance with post-treatment recommendations, management with only cytological follow-up would result in 29 residual cases of recurrent CIN3+ by 10 years and would cost £358 222 (€440 426; $574 910) (discounted) per 1000 women treated. Implementation of human papillomavirus test of cure in cytologically negative women according to the sentinel sites protocol would avert an additional 8.4 cases of CIN 3+ and reduce costs by £9388 per 1000 women treated. <b>Conclusions</b> Human papillomavirus test of cure would be more effective and would be cost saving compared with cytology only follow-up. The results of this evaluation support the full scale implementation of human papillomavirus test of cure after treatment of CIN within the NHS Cervical Screening Programme.
Lecture on the Characters of the Arterial Pulse, in their Relation to the Mode and Duration of the Contraction of the Heart in Health and Disease
Authors: J. B. Sanderson
Journal: BMJ (1867)

INTRODUCTION.THE order of sucesion of the muscular movements which take place in the heart each time that it contracts, has been very variously represented by different physiologists.More than a century ago, it was the subject of one of the most celebrted controversies* recorded in the
Checkpoint Kinase 1 Down-Regulation by an Inducible Small Interfering RNA Expression System Sensitized <i>In vivo</i> Tumors to Treatment with 5-Fluorouracil
Authors: Monica Ganzinelli, Laura Carrassa, Francesca Crippa, Michele Tavecchio, Massimo Broggini, Giovanna Damia
Journal: Clinical Cancer Research (2008)

Abstract Purpose: After DNA damage, checkpoints pathways are activated in the cells to halt the cell cycle, thus ensuring repair or inducing cell death. To better investigate the role of checkpoint kinase 1 (Chk1) in cellular response to different anticancer agents, Chk1 was knocked down in HCT-116 cell line and in its p53-deficient subline by using small interfering RNAs (siRNA). Experimental Design: Chk1 was abrogated by transient transfection of specific siRNA against it, and stable tetracycline-inducible Chk1 siRNA clones were obtained transfecting cells with a plasmid expressing two siRNA against Chk1. The validated inducible system was then translated in an in vivo setting by transplanting the inducible clones in nude mice. Results: Transient Chk1 down-regulation sensitized HCT-116 cells, p53−/− more than the p53 wild-type counterpart, to DNA-damaging agents 5-fluorouracil (5-FU), doxorubicin, and etoposide treatments, with no modification of Taxol and PS341 cytotoxic activities. Inhibition of Chk1 protein levels in inducible clones on induction with doxycycline correlated with an increased cisplatin and 5-FU activity. Such effect was more evident in a p53-deficient background. These clones were transplanted in nude mice and a clear Chk1 down-regulation was shown in tumor samples of mice given tetracycline in the drinking water by immunohistochemical detection of Chk1 protein. More importantly, an increased 5-FU antitumor activity was found in tumors with the double Chk1 and p53 silencing. Conclusions: These findings corroborate the fact that Chk1 protein is a molecular target to be inhibited in tumors with a defective G1 checkpoint to increase the selectivity of anticancer treatments.
Dragon Enhances BMP Signaling and Increases Transepithelial Resistance in Kidney Epithelial Cells
Authors: Yin Xia, Jodie L. Babitt, Richard Bouley, Ying Zhang, Nicolas Da Silva, Shanzhuo Chen, Zhenjie Zhuang, Tarek A. Samad, Gary J. Brenner, Jennifer L. Anderson, Charles C. Hong, Alan L. Schneyer, Dennis Brown, Herbert Y. Lin
Journal: Journal of the American Society of Nephrology (2010)

The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.
Identification of Small Molecules that Sensitize Resistant Tumor Cells to Tumor Necrosis Factor-Family Death Receptors
Authors: Aaron D. Schimmer, Michael P. Thomas, Rose Hurren, Marcela Gronda, Maurizio Pellecchia, Gregory R. Pond, Marina Konopleva, Debbie Gurfinkel, Imtiaz A. Mawji, Ewan Brown, John C. Reed
Journal: Cancer Research (2006)

Abstract Two major pathways for apoptosis have been identified, involving either mitochondria (intrinsic) or tumor necrosis factor (TNF)-family death receptors (extrinsic) as initiators of caspase protease activation and cell death. Because tumor resistance to TNF-family death receptor ligands is a common problem, helping malignant cells evade host immune defenses, we sought to identify compounds that selectively sensitize resistant tumor cells to death receptor ligands. We screened a 50,000-compound library for agents that enhanced anti-FAS antibody–mediated killing of FAS-resistant PPC-1 prostate cancer cell, then did additional analysis of the resulting hits to arrive at eight compounds that selectively sensitized PPC-1 cells to anti-FAS antibody (extrinsic pathway agonist) without altering sensitivity to staurosporine and etoposide (VP-16; intrinsic pathway agonists). These eight compounds did not increase Fas surface levels and also sensitized PPC-1 cells to apoptosis induced by TNF-family member TNF-related apoptosis-inducing ligand, consistent with a post-receptor mechanism. Of these, two reduced expression of c-FLIP, an intracellular antagonist of the extrinsic pathway. Characterization of the effects of the eight compounds on a panel of 10 solid tumor cell lines revealed two structurally distinct compounds that frequently sensitize to extrinsic pathway agonists. Structure-activity relation studies of one of these compounds revealed a pharmacophore from which it should be possible to generate analogues with improved potency. Altogether, these findings show the feasibility of identifying compounds that selectively enhance apoptosis via the extrinsic pathway, thus providing research tools for uncovering resistance mechanisms and a starting point for novel therapeutics aimed at restoring sensitivity of tumor cells to immune effector mechanisms. (Cancer Res 2006; 66(4): 2367-75)