tbuckley/cabot-search huggingface dataset:
Beneficial Effects of Fibrates on Apolipoprotein A-I Metabolism Occur Independently of Any Peroxisome Proliferative Response
Authors: Nathalie Hennuyer, Philippe Poulain, Lise Madsen, Rolf K. Berge, Louis-Marie Houdebine, Didier Branellec, Jean-Charles Fruchart, Catherine Fiévet, Nicolas Duverger, Bart Staels
Journal: Circulation (1999)

Background —In humans, fibrates are frequently used normolipidemic drugs. Fibrates act by regulating genes involved in lipoprotein metabolism via activation of the peroxisome proliferator-activated receptor-α (PPARα) in liver. In rodents, however, fibrates induce a peroxisome proliferation, leading to hepatomegaly and possibly hepatocarcinogenesis. Although this peroxisome proliferative response appears not to occur in humans, it remains controversial whether the beneficial effects of fibrates on lipoprotein metabolism can occur dissociated from such undesirable peroxisomal response. Here, we assessed the influence of fenofibrate on lipoprotein metabolism and peroxisome proliferation in the rabbit, an animal that, contrary to rodents and similar to humans, is less sensitive to peroxisome proliferators. Methods and Results —First, we demonstrate that in normal rabbits, fenofibrate given at a high dose for 2 weeks does not influence serum concentrations or intestinal mRNA levels of the HDL apolipoprotein apoA-I. Therefore, the study was continued with human apoA-I transgenic rabbits that overexpress the human apoA-I gene under control of its homologous promoter, including its PPAR-response elements. In these animals, fenofibrate increases serum human apoA-I concentrations via an increased expression of the human apoA-I gene in liver. Interestingly, liver weight or mRNA levels and activity of fatty acyl-CoA oxidase, a rate-limiting and marker enzyme of peroxisomal β-oxidation, remain unchanged after fenofibrate. Conclusions —Expression of the human apoA-I transgene in rabbit liver suffices to confer fibrate-mediated induction of serum apoA-I. Furthermore, these data provide in vivo evidence that the beneficial effects of fibrates on lipoprotein metabolism occur mechanistically dissociated from any deleterious activity on peroxisome proliferation and possibly hepatocarcinogenesis.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 48
Authors: A Vernec, S J Stear, L M Burke, L M Castell
Journal: British Journal of Sports Medicine (2013)

As we end this series of reviews of supplements and sports foods, it is fitting that the last words should come from the World Anti-Doping Agency. After all, the contravention of anti-doping rules due to the ingestion of prohibited substances that are ingredients or contaminants of some supplements and sports foods is a key issue which must be taken into account whenever an athlete decides whether or not to use such products.

### A Vernec

Athletes have a long history of using substances in an attempt to gain an advantage in sporting competitions. The ancient Greeks and Romans used herbs, fungi, poppy seeds and stimulants such as strychnine in order to boost performance.1 In the modern era, this practice continued mostly with the use of stimulants and narcotics. Sports federations took notice and in 1928 the International Association of Athletics Federations (IAAF) became the first federation to prohibit the use of performance-enhancing drugs (PEDs), although there would be no testing in sport for another 40 years.2

Amphetamine use was involved in the deaths of cyclists Knud Jensen and Tommy Simpson in the 1960 Olympic Games and the 1967 Tour de France respectively: this spurred the development of the International Olympic Commissions (IOC) Medical Commission, which published the first IOC Prohibited List in 1967. This became the de facto Prohibited List for Olympic Sport Federations. The ‘Festina affair’ (1998 Tour de France), where a team trainer's car was found to contain a panoply of PEDs, was the catalyst to create a new organisation to harmonise, coordinate and promote the fight against doping in sport in all its forms.3 The IOC convened the first World Conference in Doping in Sport in 1999, which resulted in the formation of the World Anti-Doping Agency (WADA).

WADA is a unique, independent body representing equally sport and …
BMS-536924 Reverses IGF-IR-Induced Transformation of Mammary Epithelial Cells and Causes Growth Inhibition and Polarization of MCF7 Cells
Authors: Beate C. Litzenburger, Hyun-Jung Kim, Isere Kuiatse, Joan M. Carboni, Ricardo M. Attar, Marco M. Gottardis, Craig R. Fairchild, Adrian V. Lee
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study aimed to test the ability of a new insulin-like growth factor receptor (IGF-IR) tyrosine kinase inhibitor, BMS-536924, to reverse the ability of constitutively active IGF-IR (CD8-IGF-IR) to transform MCF10A cells, and to examine the effect of the inhibitor on a range of human breast cancer cell lines. Experimental Design: CD8-IGF-IR-MCF10A cells were grown in monolayer culture, three-dimensional (3D) culture, and as xenografts, and treated with BMS-536924. Proliferation, cell cycle, polarity, and apoptosis were measured. Twenty-three human breast cancer cell lines were treated in monolayer culture with BMS-536924, and cell viability was measured. MCF7, MDA-MB-231, and MDA-MB-435 were treated with BMS-536924 in monolayer and 3D culture, and proliferation, migration, polarity, and apoptosis were measured. Results: Treatment of CD8-IGF-IR-MCF10A cells grown in 3D culture with BMS-536924 caused a blockade of proliferation, restoration of apical-basal polarity, and enhanced apoptosis, resulting in a partial phenotypic reversion to normal acini. In monolayer culture, BMS-536924 induced a dose-dependent inhibition of proliferation, with an accumulation of cells in G0/G1,, and completely blocked CD8-IGF-IR–induced migration, invasion, and anchorage-independent growth. CD8-IGF-IR-MCF10A xenografts treated with BMS-536924 (100 mg/kg/day) showed a 76% reduction in xenograft volume. In a series of 23 human breast cancer cell lines, BMS-536924 inhibited monolayer proliferation of 16 cell lines. Most strikingly, treatment of MCF7 cells grown in 3D culture with BMS-536924 caused blockade of proliferation, and resulted in the formation of hollow polarized lumen. Conclusions: These results show that the new small molecule BMS-536924 is an effective inhibitor of IGF-IR, causing a reversion of an IGF-IR–mediated transformed phenotype.
What's the Alternative? The Worldwide Web of Integrative Medicine
Authors: Ranjana Srivastava
Journal: New England Journal of Medicine (2012)

A young woman wins a blood test at an integrative medicine seminar and is told she has circulating tumor cells, indicating advanced cancer, and requires a $6,000 course of IV vitamin C. Petrified, she is difficult to dissuade. What's a respectable oncologist to do?
Note on a Case of Pseudo-Hypertrophic Paralysis (?): Recovery
Authors: H. Donkin
Journal: BMJ (1882)

that dirty-red, slimy, bad smelling, never abundant expectoration which hysterical women with phthisis often exhibit at the bottoms of their spittoons; this may be left to itself.The other exception is a serious one; it comprises those forms of hzemoptysis, usually copious and angry, occurring in advanced and very chronic cases where there is a con- siderable amount of fibroid induration.In such patients, notable dyspncea on exertion has for a long time past been a prominent sym- ptom, and respiration has been maintained by a very small extent of lung-substance.These cases are open to a special danger-that of fatal embolism in the right chambers of the heart or the pulmonary artery.Not uncommonly, the course followed is for the bleeding gradually to abate in quantity, remaining, nevertheless, of the same angry red; then urgent dyspncea suddenly sets in, and death takes place within forty-eight hours.
Germany suspends decision to stop some hospitals treating very low birth weight babies
Authors: A. Tuffs
Journal: BMJ (2011)

The German healthcare system has decided to temporarily lift the recently announced ban on some small hospitals caring for babies with a very low birth weight.

The ban, which was announced in June 2010 and was due to come into force on 1 January, would have allowed only 70 hospitals to care for the 8000 very low birth weight babies born in Germany every year. Hospitals that cared for fewer than …
Reply from Authors re: Andrew J. Vickers, Michael J. Pencina. Prostate-specific Antigen Velocity: New Methods, Same Results, Still No Evidence of Clinical Utility. Eur Urol 2013;64:394–6
Authors: David D. Ørsted, Stig E. Bojesen, Pia R. Kamstrup, Børge G. Nordestgaard
Journal: European Urology (2013)
UK proposes reforms for research ethics committees
Authors: Susan Mayor
Journal: BMJ (2005)

NHS research ethics committees (RECs) should work more closely with each other, have a clearer remit, and improve training for their members. These were the recommendations of a report published this week that was designed to streamline the procedures for ethical review of research proposals for studies to be done in the NHS.

The committees give independent advice on whether proposals for research studies in the NHS comply with ethical standards. The report, from the UK Department of Health, was developed in response to criticisms from researchers that the committees are uncoordinated, application procedures are time consuming, and decisions are unpredictable. …
Spinocerebellar Degeneration Associated with a Selective Defect of Vitamin E Absorption
Authors: A.E. Harding, S. Matthews, S. Jones, C.J.K. Ellis, I.W. Booth, D.P.R. Muller
Journal: New England Journal of Medicine (1985)

A NUMBER of recent reports have suggested that some patients with chronic fat malabsorption have spinocerebellar degeneration secondary to a severe and prolonged deficiency of vitamin E. The clinical features of this syndrome comprise progressive ataxia of gait, incoordination of the limbs, areflexia, and distal loss of proprioception and vibration sense. Dysarthria, ophthalmoplegia, pigmentary retinopathy, generalized muscle weakness, extensor plantar responses, and superficial sensory loss occur in some cases.1 A relation between neurologic dysfunction and vitamin E deficiency was first suggested by Binder and colleagues in a report on patients with chronic steatorrhea,2 and subsequently confirmed in patients with abetalipoproteinemia, . . .
Shoulder pain: diagnosis and management in primary care
Authors: Caroline Mitchell, Ade Adebajo, Elaine Hay, Andrew Carr
Journal: BMJ (2005)

Compromised shoulder movement due to pain, stiffness, or weakness can cause substantial disability and affect a person's ability to carry out daily activities (eating, dressing, personal hygiene) and work.w1 Self reported prevalence of shoulder pain is estimated to be between 16% and 26%; it is the third most common cause of musculoskeletal consultation in primary care, and approximately 1% of adults consult a general practitioner with new shoulder pain annually. 1Occupations as diverse as construction work and hairdressing are associated with a higher risk of shoulder disorders.Physical factors such as lifting heavy loads, repetitive movements in awkward positions, and vibrations influence the level of symptoms and disability, and psychosocial factors are also important.w1 Recent studies suggest that chronicity and recurrence are common. 2 3 Common shoulder disorders exhibit similar clinical features, and the lack of consensus on diagnostic criteria and concordance in clinical assessment complicates treatment choices. 3w2-w5 This review proposes an evidence based approach using a simplified classification of shoulder problems, incorporating diagnostic techniques applicable to a primary care consultation and a "red flag" system to identify potentially serious disease. Sources and selection criteriaWe incorporated the latest consensus from systematic reviews and publications identified by a literature search through Medline, CINAHL, AMED, the Cochrane Library (Central, CDSR, HTA, DARE), Clinical Evidence, Best Evidence, Embase, British Nursing Index, PEDro, w6 Web of Science (social science and science citation indexes), and bmj.com.The search strategy included the terms "shoulder pain", "rotator cuff disorder", "rotator cuff tear", "frozen shoulder", and "primary care".We found six published systematic reviews of interventions for shoulder disorders and one health technology assessment systematic review of diagnostic tests for the assessment of shoulder pain. 4-10A topic search within Clinical Evidence identified the section "Shoulder pain." 11We identified and critically appraised other key publications in peer reviewed journals that were relevant to primary care or published since the latest systematic reviews.
(27) Cutaneous ectopic schistosomiasis
Authors: D.M. MacDonald, J.G.L. Morrison, M. Greaves
Journal: British Journal of Dermatology (2006)

Journal Article (27) Cutaneous ectopic schistosomiasis Get access D.M. MacDonald, D.M. MacDonald Sr John's Hospital far Diseases of the Skin, London WC2 Search for other works by this author on: Oxford Academic Google Scholar J.G.L. Morrison, J.G.L. Morrison Sr John's Hospital far Diseases of the Skin, London WC2 Search for other works by this author on: Oxford Academic Google Scholar M. Greaves M. Greaves Sr John's Hospital far Diseases of the Skin, London WC2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue s14, 1 December 1976, Pages 57–58, https://doi.org/10.1111/j.1365-2133.1976.tb07915.x Published: 01 December 1976
Searching high and low: Cancer stem cells in the eye
Authors: Konrad L. Streetz, Arndt Vogel
Journal: Hepatology (2008)

This study characterized cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) cell lines, tumor specimens, and blood samples. The CD90+ cells, but not the CD90− cells, from HCC cell lines displayed tumorigenic capacity. All the tumor specimens and 91.6% of blood samples from liver cancer patients bore the CD45−CD90+ population, which could generate tumor nodules in immunodeficient mice. The CD90+CD44+ cells demonstrated a more aggressive phenotype than the CD90+CD44− counterpart and formed metastatic lesions in the lung of immunodeficient mice. CD44 blockade prevented the formation of local and metastatic tumor nodules by the CD90+ cells. Differential gene expression profiles were identified in the CD45−CD90+ and CD45−CD90− cells isolated from tissue and blood samples from liver cancer patients and controls.
Deaths from smoking: the avoidable holocaust
Authors: T. Delamothe
Journal: BMJ (2012)

Start by kicking British American Tobacco and Imperial Tobacco out of the country



At the beginning of the 20th century hardly anyone smoked cigarettes. By 1948 82% of men in Britain were smoking some form of tobacco. By 2009 only 22% were. Extrapolate forwards this rate of decline and by 2031 Britain should have no male smokers. (Women are on a slightly different trajectory.)

Would that it were so simple. A meeting to mark the 50th anniversary of the Royal College of Physicians’ report Smoking and Health ( BMJ 2012;344:e1676, doi:10.1136/bmj.e1676) offered three main messages on how change on this scale was achieved. Firstly, there was no single magic bullet: controls on marketing and sales, health warnings on packs, and prohibition of smoking in public places all played a part. Secondly, legislation worked much better than persuasion. And lastly, tobacco companies fought the controls every step of the way.

Yet these companies are purveyors of death on an industrial scale. In the 50 years since Smoking and Health ’s publication smoking has killed six million people in the United Kingdom. It remains the country’s number one cause of premature death, responsible for killing about 100 000 people a …
Bone Marrow and Bone Tissue: Color Atlas of Clinical Histopathology
Authors: William R. Best
Journal: JAMA (1972)

Burkhardt has led in developing a system of obtaining and examining sections incorporating cortex, bone spicules, and bone marrow from the iliac crest. This system guarantees an ample, undistorted piece of tissue. It utilizes newer techniques of fixation, sectioning, and staining, so that one may readily study both histology and cytology of the bone and marrow; but it involves more of a surgical procedure, special processing equipment, and a considerably longer period for specimen preparation than does marrow aspiration. The author believes that his system produces material for study superior to those obtained by marrow aspiration and the generally used methods for marrow section. This volume is his chef d'oeuvre for promoting his system and for guiding those who would use it. The technique involves removing a cylinder of bone and marrow about 4 × 18 mm. After special embedding it is cut into serial sections of 1μ to 3μ
The Effect of Acetylcholine and Potassium on Repolarization of the Heart *
Authors: Charles Fisch, Suzanne B. Knoebel, Harvey Feigenbaum
Journal: Journal of Clinical Investigation (1964)

Acetylcholine has been shown to have an effect on the action potentials of mammalian atrial muscle, the sinoatrial and the atrioventricular nodes, and on the action potential of frog ven- tricles (1-4).On the other hand, the action po- tential of mammalian ventricle has been found to be highly resistant to acetylcholine.Only very slight changes were noted in the presence of enor- mous concentrations of the drug (4-6).The purpose of this communication is to pre- sent electrocardiographic evidence indicating a) that acetylcholine exerts a consistent effect on re- polarization of the ventricles in the intact dog and that this effect is independent of the heart rate, ventricular arrhythmias, and atrioventricular (AV) or intraventricular conduction delays, and b) that the effect of acetylcholine on repolarization is augmented by increasing the level of plasma potassium (K). MethodsEleven experiments were performed with seven mon- grel dogs weighing 10 to 14 kg.The animals were anesthetized with either pentobarbital, 30 mg per kg iv, or a combination of morphine sulfate, 2.5 mg per kg im, followed by pentobarbital, 15 mg per kg iv.Ventila- tion was maintained through the use of a Harvard respirator.A bilateral cervical vagotomy was per- formed, and an arterial catheter was placed just above the aortic valves.Blood pressure was continuously re- corded through a Cournand needle in the femoral artery.The entire experiment was monitored with an oscilloscope, and permanent records were obtained with a direct- *
Human three-dimensional engineered neural tissue reveals cellular and molecular events following cytomegalovirus infection
Authors: Érika Cosset, Yannick Martinez, Olivier Preynat-Seauve, Johannes-Alexander Lobrinus, Caroline Tapparel, Samuel Cordey, Hedi Peterson, Tom J. Petty, Marilena Colaianna, Vannary Tieng, Diderik Tirefort, Andras Dinnyes, Michel Dubois-Dauphin, Laurent Kaiser, Karl-Heinz Krause
Journal: Biomaterials (2015)
Estradiol blocks the induction of CD40 and CD40L expression on endothelial cells and prevents neutrophil adhesion: An ERα-mediated pathway
Authors: P GERALDES, S GAGNON, S HADJADJ, Y MERHI, M SIROIS, I CLOUTIER, J TANGUAY
Journal: Cardiovascular Research (2006)

Interferon gamma (IFN-gamma) was shown to induce CD40 and CD40L expression on endothelial cells (ECs) and consequently to promote neutrophil adhesion. The pro- and anti-inflammatory effects of estrogens are well recognized but their role on the regulation of CD40 and CD40L expression on ECs remains undefined.Treatment of porcine aortic endothelial cells (PAEC) with IFN-gamma for 24 h enhanced CD40 and CD40L expression by 97% and 78%, respectively. Pretreatment of PAEC with 17-beta-estradiol (17betaE) for 24 h prevented the latter expression of CD40/CD40L. Treatment of PAEC with antisense oligomers targeting ERalpha mRNA attenuated the ability of 17betaE to inhibit the IFN-gamma-induced CD40 and CD40L protein expression. The IFN-gamma activation pathway of CD40 is known to involve the phosphorylation of the Janus activated kinase (JAK) and the signal transducer and activator of transcription 1 (Stat1). 17betaE, acting via the estrogen receptor alpha (ERalpha), abrogated IFN-gamma-mediated effects on Stat1 but failed to inhibit Jak1 and Jak2 phosphorylation. Furthermore, 17betaE prevented neutrophil adhesion induced by IFN-gamma.In summary, 17betaE binding to ERalpha blocked IFN-gamma-induced Stat1 phosphorylation, CD40 and CD40L protein expression, and neutrophil adhesion onto ECs.
Genetic Instability Caused by Loss of MutS Homologue 3 in Human Colorectal Cancer
Authors: Astrid C. Haugen, Ajay Goel, Kanae Yamada, Giancarlo Marra, Thuy-Phuong Nguyen, Takeshi Nagasaka, Shinsaku Kanazawa, Junichi Koike, Yoshinori Kikuchi, Xiaoling Zhong, Michitsune Arita, Kazutoshi Shibuya, Mitsuo Oshimura, Hiromichi Hemmi, C. Richard Boland, Minoru Koi
Journal: Cancer Research (2008)

Abstract Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency. High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2. CRC with low levels of MSI (MSI-L) exists; however, its molecular basis is unclear. There is another type of MSI—elevated microsatellite alterations at selected tetranucleotide repeats (EMAST)—where loci containing [AAAG]n or [ATAG]n repeats are unstable. EMAST is frequent in non-CRCs; however, the incidence of EMAST and its cause in CRC is not known. Here, we report that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non–MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non–MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2% to 50% of the total tumor cell population, the tissues exhibiting EMAST contained more MSH3-negative cells (average, 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the concept that MSH3 deficiency causes EMAST or EMAST with low levels of MSI at loci with dinucleotide repeats in CRC. [Cancer Res 2008;68(20):8465–72]
The proteins encoded by the VpreB and lambda 5 pre-B cell-specific genes can associate with each other and with mu heavy chain.
Authors: H Karasuyama, A Kudo, F Melchers
Journal: The Journal of Experimental Medicine (1990)

The murine pre-B cell-specific genes VpreB and lambda 5, as well as the murine gene for mu heavy chain, were introduced into Ltk- fibroblast cells which normally do not express these genes. Stable transfectants carrying these genes produced the corresponding proteins of 15.5, 21.5, and 75 kD. They secreted the three proteins as a triple complex that could be immunoprecipitated by mu heavy chain-specific antibodies, consisting of one VpreB, one lambda 5, and one mu heavy chain. The mu heavy chain and lambda 5 were disulfide-bonded with each other, while the VpreB protein was noncovalently associated. These experiments proved that the VpreB, lambda 5 and mu H chain proteins can form a heavy/light chain-like heterocomplex.