tbuckley/cabot-search huggingface dataset:
PPARα Activators Inhibit Cytokine-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells
Authors: Nikolaus Marx, Galina K. Sukhova, Tucker Collins, Peter Libby, Jorge Plutzky
Journal: Circulation (1999)

Adhesion molecule expression on the endothelial cell (EC) surface is critical for leukocyte recruitment to atherosclerotic lesions. Better understanding of transcriptional regulation of adhesion molecules in ECs may provide important insight into plaque formation. Peroxisome proliferator-activated receptor-alpha (PPARalpha), a member of the nuclear receptor family, regulates gene expression in response to certain fatty acids and fibric acid derivatives. The present study investigated PPARalpha expression in human ECs and their regulation of vascular cell adhesion molecule-1 (VCAM-1).Immunohistochemistry revealed that human carotid artery ECs express PPARalpha. Pretreatment of cultured human ECs with the PPARalpha activators fenofibrate or WY14643 inhibited TNF-alpha-induced VCAM-1 in a time- and concentration-dependent manner, an effect not seen with PPARgamma activators. Both PPARalpha activators decreased cytokine-induced VCAM-1 mRNA expression without altering its mRNA half-life. Transient transfection of deletional VCAM-1 promoter constructs and electrophoretic mobility shift assays suggest that fenofibrate inhibits VCAM-1 transcription in part by inhibiting NF-kappaB. Finally, PPARalpha activators significantly reduced adhesion of U937 cells to cultured human ECs.Human ECs express PPARalpha, a potentially important regulator of atherogenesis through its transcriptional control of VCAM-1 gene expression. Such findings also have implications regarding the clinical use of lipid-lowering agents, like fibric acids, which can activate PPARalpha.
A panic measure with hidden hazards
Authors: N. Ellis
Journal: BMJ (1980)

The first important strike in the NHS was in 1968 when medical laboratory technicians stopped work for one day over a pay dispute. Two years later elec tricians took industrial action and since then almost all the major groups of Health Service employees?in cluding doctors and nurses?have taken part in some form of protest action. So from perhaps the most quiescent and undeveloped industrial relations system among State enter prises the NHS has become one of the most active and strike prone in Britain. Though the widespread national disputes over pay that oc curred last winter may be more memorable, the most typical strike is localised, unofficial, and usually focused on issues quite unconnected wTith pay. Because local disputes of this kind were becoming common place the former Secretary of State for Social Services, Mr David Ennals, took the initiative of calling a round table conference of those who were principally concerned?repre sentatives of the unions (including the BMA) and the manage ment.1 The conference discussed whether agreement could be reached on a new NHS disputes procedure which would cut to a minimum the number of disputes that led to unnecessary industrial action. Afterwards, in October 1978, the DHSS published details of a proposed procedure.This was designed to cover local disputes and problems other than those concerned with pay. The DHSS statement gave as examples of the issues to be covered : duty rotas, staffing levels on the wards, arrange ments for parking bicycles, or even personality clashes between staff. In short, it was intended to cover a wide range of residual matters outside the Whitley Council system, most of which had been traditionally decided by management without any kind of formal consultation or negotiations with representatives of the staff affected. Since the round table initiative the proposed local disputes procedure has been under negotiation by unions and manage ment. While some differences of opinion remain, the manage ment and the staff sides agree on the basic guidelines. Some of these are unexceptionable. It is proposed, for example, that disputes should be resolved at the lowest possible operational level with the minimum of delay; and that there should be an agreed four-stage procedure for referring the dispute upwards if the local manager cannot resolve it, firstly, to the next layer of management, then to the chief officer of the employing authority, and finally to the employing authority. Such disputes procedure is a common feature of industrial relations machinery in other organisations and industries. The proposed procedure also contains what is commonly known as a status quo provision. This requires that the arrangements extant before the dispute should be reintroduced until the dispute has been resolved? namely, the unions should withdraw sanctions and the manage ment should unscramble any change in working practices it had introduced. The intention is to provide a conciliatory climate in which the dispute may be resolved.
The epidemiology of ankle injuries occurring in English Football Association academies
Authors: D J Cloke, S Spencer, A Hodson, D Deehan
Journal: British Journal of Sports Medicine (2008)

Objective: To ascertain the epidemiology of ankle injuries in elite youth football. Design: Retrospective analysis of prospectively collected injury data from English Football Association (FA) academies. Setting: Forty-one FA football academies, between 1998 and 2006. Participants: For the complete seasons studied, a total of 14 776 players was registered from U9 to the U16 age category, a mean of 2463 players per year. All ankle injuries of sufficient severity to miss 48 h or more of training were studied, 2563 injuries in total. Main Outcome Measure: The incidence and burden of ankle injuries in this population and factors associated with injury. Results: There was a mean incidence of one ankle injury per player per year, and a mean of 20 training days and two matches were missed per ankle injury. Increased injury rates were seen in older players, in competition and later in each half of match time. Peaks in injury were observed early in the season and after the winter break. In competition, more injuries were associated with a contact situation than in training. Eighty-eight injuries (3.4%) required a lay-off of 3 months or more and in 18 (0.7%) cases the player failed to return to training. In total, 52 290 training days and 5182 match appearances were lost through ankle injury. The majority of injuries were sprains, but more severe injuries occurred accounted for 3.9% of the total. Conclusions: Ankle injuries are common in young football players and are often severe, with prolonged loss of training time. This has potential far-reaching implications, both on and off the field.
Functional evidence of persistent airway obstruction in rats following a two-hour inhalation exposure to methyl isocyanate.
Authors: M A Stevens, S Fitzgerald, M G Ménache, D L Costa, J R Bucher
Journal: Environmental Health Perspectives (1987)

Pulmonary function was assessed in male, F344 rats 1,2,4,7, and 13 weeks after a single 2-hr exposure to 0, 3, 10, or 30 ppm methyl isocyanate. No significant changes were observed in the rats exposed to 3 ppm through 13 weeks. Diffusing capacity (DLco), quasistatic lung compliance, and homogeneity of ventilation, as determined by multibreath nitrogen washout, were depressed in the rats exposed to 10 and 30 ppm by 1 week after exposure. None of the rats exposed to 30 ppm survived beyond 1 week. By 13 weeks, dramatic increases in lung volumes were observed in the rats exposed to 10 ppm, while DLco and lung compliance were only mildly affected. However, volume-specific DLco and compliance were depressed in the rats exposed to 10 ppm, suggesting that lung hyperinflation or other compensatory means of increasing lung size occurred in response to the methyl isocyanate-induced lung lesion. This group also exhibited increased expiratory times during tidal breathing and severely impaired distribution of ventilated air. Collectively, these results suggest the development and likely progression of a severe, obstructive airway lesion with associated gas trapping, and the existence of a pronounced concentration-response relationship between 3 and 10 ppm methyl isocyanate exposures.
Peanut protein in household dust is related to household peanut consumption and is biologically active
Authors: Helen A. Brough, Alexandra F. Santos, Kerry Makinson, Martin Penagos, Alick C. Stephens, Abdel Douiri, Adam T. Fox, George Du Toit, Victor Turcanu, Gideon Lack
Journal: Journal of Allergy and Clinical Immunology (2013)
Impact of Statin Therapy on Plaque Characteristics as Assessed by Serial OCT, Grayscale and Integrated Backscatter–IVUS
Authors: Kousuke Hattori, Yukio Ozaki, Tevfik F. Ismail, Masanori Okumura, Hiroyuki Naruse, Shino Kan, Makoto Ishikawa, Tomoko Kawai, Masaya Ohta, Hideki Kawai, Tousei Hashimoto, Yasushi Takagi, Junichi Ishii, Patrick W. Serruys, Jagat Narula
Journal: JACC. Cardiovascular imaging (2012)
Immunological studies of an organic anion-binding protein isolated from rat liver cell plasma membrane.
Authors: A W Wolkoff, A Sosiak, H C Greenblatt, J Van Renswoude, R J Stockert
Journal: Journal of Clinical Investigation (1985)

The mechanism of organic anion uptake by hepatocytes has kinetics that suggest facilitated diffusion, and carrier-mediated membrane transport has been postulated. In previous studies, we purified a 55,000-mol wt organic anion-binding protein (OABP) by affinity chromatography on sulfobromophthalein (BSP)-Sepharose of deoxycholate solubilized liver cell plasma membrane preparations. Using specific goat and rabbit antibodies to OABP, we have now investigated the distribution of this protein in liver fractions and other tissues by an enzyme-linked immunosorbent assay and by the immunoblot (Western blot) procedure. These studies indicated that OABP is present in significant amounts in all tissues examined except for blood. Although OABP has not as yet been isolated from each of these tissues and characterized, OABP in heart retained the ability to bind organic anions, and was purified by affinity chromatography on BSP-sepharose. In liver, OABP was membrane bound and remained so after extraction with 0.9 M NaCl, which suggests that it is an intrinsic membrane protein. OABP did not have a ubiquitous subcellular distribution within the hepatocyte. Preparation of subfractions of liver cell plasma membrane revealed that OABP is present in the sinusoidal and absent from the canalicular membrane. Immunofluorescence studies performed in short-term cultured hepatocytes suggest that OABP is associated with the surface of these cells and does not have a significant intracellular distribution.
MPs’ report criticises influence of drugs industry on GP prescribing
Authors: Zosia Kmietowicz
Journal: BMJ (2008)

Too many GPs are influenced by the pharmaceutical industry, which spends £850m (€1130m; $1670m) every year on marketing its products in primary care, says a report from the Public Accounts Committee, the government’s spending watchdog. 

And the NHS spends at least £200m more than it should on medicines because GPs do not heed official guidelines and continue to prescribe branded medicines rather than generics, says the report.

The committee’s comments follow a survey by the National Audit Office which found that one in five GPs said their prescribing choices were swayed …
A Case of Osteomalacia in a Child
Authors: J. S. Bury
Journal: BMJ (1884)

THE specimens of tibia, radius, ulna, and rib, exhibited to-day, were obtained from a female child aged 8 months.When first seen, about a fortnight before death, the child was much wasted, and' seery s_iall for its ge; it weighed 5 lbs., and the lengthlof the bodyr was 45 centimbtres (about 17.75 inches),,which is at least 10 centi-' metres, or about four inclies, shorter thasn it should be at that age.'All the limbs were bent; the tibisew'ere strongly arched forwards, and felt thickened, the femora were bent outwards and backwards,' and the arms and forearms presented an outward curve.The chest was fairly shaped; there were no grooves, and no detectable enlarge- 'i 1 -.f;r z -f Il-'n,:Ls i..id .
Retinoic acid receptor β2 promotes functional regeneration of sensory axons in the spinal cord
Authors: Liang-Fong Wong, Ping K Yip, Anna Battaglia, John Grist, Jonathan Corcoran, Malcolm Maden, Mimoun Azzouz, Susan M Kingsman, Alan J Kingsman, Nicholas D Mazarakis, Stephen B McMahon
Journal: Nature Neuroscience (2005)
Hernia surgery is cost effective, finds UK study
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Elective hernia surgery presents value for money for the NHS, a study has found, contradicting recent guidelines suggesting that the operation was of “low clinical value” and that commissioners should consider restricting it.

The latest analysis used patient reported outcome measures (PROMs) from nearly 17 500 patients who had a hernia operation in England between 1 April 2009 and 31 Match 2010. These data have been collected routinely in the NHS since 2009, before and at least three months after patients undergo hernia repair.

Researchers from the think tank the King’s Fund and Imperial College London combined these outcomes with costs …
Abstract 5056: HuGAL-FR21, a humanized monoclonal antibody to Fibroblast Growth Factor Receptor 2, effectively inhibits the growth of gastric tumor xenografts
Authors: Hangil Park, Lihong Wang, Sophea Chhim, Yi Ding, Jin Kim
Journal: Cancer Research (2011)

Abstract The family of 22 fibroblast growth factors include potent mitogenic and angiogenic factors believed to play a role in the growth of many tumors. The various FGFs bind to only four tyrosine kinase signaling receptors, Fibroblast Growth Factor Receptors 1-4 (FGFR1-4). FGFR2 is a major cellular receptor for FGF2 (basic FGF), FGF7 (keratinocyte growth factor, KGF) and FGF10; and mutation or overexpression of FGFR2 is associated with a number of cancers, notably endometrial cancer and gastric carcinoma. In this study, we explored the therapeutic potential of the HuGAL-FR21 humanized monoclonal antibody (mAb) derived from our blocking anti-FGFR2 mAb, GAL-FR21. We previously showed that GAL-FR21 binds to only the FGFR2IIIb isoform of FGFR2, which is expressed on epithelial tissues and thus more commonly on carcinomas. Using well-established humanization techniques, GAL-FR21 was humanized to create HuGAL-FR21, which binds human FGFR2IIIb with at least as high affinity as GAL-FR21. HuGAL-FR21, like GAL-FR21, also bound well to monkey and mouse FGFR2IIIb, facilitating study of this mAb in animal models. In functional assays, HuGAL-FR21 inhibited binding of FGF2, FGF7 and FGF10 to FGFR2IIIb as completely as GAL-FR21. And HuGAL-FR21 inhibited FGF7 or FGF10-induced proliferation of the Ba/F3 cells transfected with FGFR2IIIb, actually better than GAL-FR21. Finally, HuGAL-FR21 inhibited phosphorylation of cellular FGFR2 induced by FGF7 and FGF10 as well as GAL-FR21. There are two major types of gastric cancer, well-differentiated and poorly differentiated, and published results show that many poorly differentiated tumors overexpress FGFR2, which is in fact the oncogenic driver for these tumors. We therefore tested the ability of HuGAL-FR21 to inhibit growth of xenografts of two cell lines, SNU-16 and OCUM-2M, derived from FGFR2-overexpressing, poorly differentiated gastric tumors. HuGAL-FR21, administered i.p. at 2.5 or 5 mg/kg twice per week, strongly inhibited the growth of established xenografts of both these cell lines. We conclude that FGFR2 is a promising molecular target, and that HuGAL-FR21 is a viable clinical candidate for the treatment of gastric and possibly other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5056. doi:10.1158/1538-7445.AM2011-5056
Modern Occupational Medicine—
Authors: Melvin N. Newquist
Journal: JAMA (1961)

This publication represents an extensive revision of the first edition, published in 1954, and the addition of new chapters. Among the 23 contributors, all of the du Pont organization, are medical administrators, psychiatrists, a surgeon, a dermatologist, chemical engineers, industrial hygiene engineers, a toxicologist, a lawyer, and a statistician. The authors have slanted their contributions toward the chemical industry where toxicological hazards are important, as evidenced by their recommendation of a full-time physician in a plant of 1,000 employees. Nevertheless, the principles of organization and procedures, as expressed in this book, are generally applicable. The toxicity and biological action of chemicals, singly and in groups, are described, as well as the treatment of accidental poisoning. This authoritative and well-rounded book is a valuable source of information not only for industrial physicians but also for all persons concerned with occupational health, including physicians in rural areas who deal with the farmer
Surprises from the crystal structure of the hepatitis C virus NS2-3 protease
Authors: Jerome Gouttenoire, Darius Moradpour, François Penin
Journal: Hepatology (2006)

Abstract Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes 2 proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at 4 downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here, we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 Å resolution. The structure reveals a dimeric cysteine protease with 2 composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the 2 active sites, predicting an inactive postcleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design.
Alcoholism and drug dependence in doctors and nurses.
Authors: M. M. Glatt
Journal: BMJ (1968)

MMICJOULreabsorption either in their patient with primary aldosteronism or in their earlier studies on the effect of aldosterone in normal subjects.2At the present time it is believed, on evidence which is mainly derived from animal experiments, that potassium secretion into the colon is passive and occurs as a result of the negative intraluminal potential created by active absorption of sodium ion.If this view is correct the primary action of aldosterone is likely to be on sodium, as appears to be the case in all other tissues, including the renal tubule,4 in which aldosterone influences electrolyte transport.The fact that Levitan and Ingelfinger,5' using essentially the same method as that employed by Mr. Shields and his colleagues, found an effect on sodium but not on potassium suggests that small differences in experimental technique have a pro- found effect on the results of this type of experiment.The accompanying Figure, from an experi- ment which Dr. R. B. I. Morrison, Miss Ann Metcalfe-Gibson, and myself performed in 1962, confirms that aldosterone indeed has an effect on net sodium absorption from the human colon.
The Roles of Vitamin D in Skeletal Muscle: Form, Function, and Metabolism
Authors: Christian M. Girgis, Roderick J. Clifton-Bligh, Mark W. Hamrick, Michael F. Holick, Jenny E. Gunton
Journal: Endocrine Reviews (2012)

Abstract Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.
Agranulocytosis Associated With Disopyramide Therapy
Authors: Marcel E. Conrad
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Disopyramide phosphate (Norpace) is a newly available type 1 antiarrhythmic drug.<sup>1</sup>It is not chemically related to other antiarrhythmic drugs in structure. Similar to quinidine and procainamide, it is useful in the treatment of ectopic ventricular contractions and episodes of ventricular tachycardia and is purported to have less adverse reactions in therapeutic dosages.<sup>2</sup>We have treated a patient who had agranulocytosis on two occasions after the administration of disopyramide. <h3>Report of a Case.—</h3> A 61-year-old man underwent a cholecystectomy during April 1978. During convalescence from surgery ventricular bigeminy developed and was initially treated with quinidine. Inadequate control of his arrhythmia was obtained, and quinidine therapy was discontinued on April 28. Therapy with disopyramide phosphate and procainamide hydrochloride was initiated; a normal WBC count and differential cell count were obtained on that date. On May 11, fever with a suppurative tonsillitis developed; the patient had a