tbuckley/cabot-search huggingface dataset:
Cancer survival in UK and Denmark lags behind that in Australia, Canada, and Sweden
Authors: Z. Kmietowicz
Journal: BMJ (2010)

Late diagnosis means that patients in the United Kingdom and Denmark are less likely to survive bowel, lung, breast, or ovarian cancer than patients in Australia, Canada, and Sweden, a new study concludes.

The study of the records of 2.4 million adults who were given a diagnosis of one of the cancers between 1995 and 2007 found that patients were living longer in 2007 in all the six countries studied than they were in the late 1990s ( Lancet , doi:10.1016/S0140-6736(10)62231-3). But survival rates were persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark and the United Kingdom (excluding Scotland), especially in the first year after diagnosis and in people aged over 65.

Many countries have implemented …
Gordon William Taylor
Authors: Phil Simmons
Journal: BMJ (2004)

Former general practitioner Reading (b 1928; q Manchester 1952; MBE, FRCGP), died from bronchopneumonia and Parkinson's disease on 18 June 2004.​2004.




Figure 1




Five years after qualification Gordon settled in Reading as a general practitioner, helping to build up a practice on a new housing estate. In 1981 he became a magistrate. He was actively involved in medical politics, and chaired the BMA ethics committee for a number of years. He had a special interest in the training of medical secretaries, and in 1997 was made a fellow of the Association of Medical Secretaries and Practice Administrators. Parkinson's disease forced him to take early retirement in 1988. A dedicated Christian, he worshipped at the same church for over 50 years. He leaves a wife, Joan; three children; and seven grandchildren.
Hepatocyte‐specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure†
Authors: Ying Chen, Yi Yang, Marian L. Miller, Dongxiao Shen, Howard G. Shertzer, Keith F. Stringer, Bin Wang, Scott N. Schneider, Daniel W. Nebert, Timothy P. Dalton
Journal: Hepatology (2007)

Oxidative stress is considered to be a critical mediator in liver injury of various etiologies. Depletion of glutathione (GSH), the major antioxidant in liver, has been associated with numerous liver diseases. To explore the specific role of hepatic GSH in vivo, we targeted Gclc, a gene essential for GSH synthesis, so that it was flanked by loxP sites and used the albumin-cyclization recombination (Alb-Cre) transgene to disrupt the Gclc gene specifically in hepatocytes. Deletion within the Gclc gene neared completion by postnatal day (PND)14, and loss of GCLC protein was complete by PND21. Cellular GSH was progressively depleted between PND14 and PND28—although loss of mitochondrial GSH was less severe. Nevertheless, ultrastructural examination of liver revealed dramatic changes in mitochondrial morphology; these alterations were accompanied by striking decreases in mitochondrial function in vitro, cellular ATP, and a marked increase in lipid peroxidation. Plasma liver biochemistry tests from these mice were consistent with progressive severe parenchymal damage. Starting at PND21, livers from hepatocyte-specific Gclc knockout [Gclc(h/h)] mice showed histological features of hepatic steatosis; this included inflammation and hepatocyte death, which progressed in severity such that mice died at approximately 1 month of age due to complications from liver failure. Conclusion: GSH is essential for hepatic function and loss of hepatocyte GSH synthesis leads to steatosis with mitochondrial injury and hepatic failure. (HEPATOLOGY 2007.)
Abstract 4453: Development and characterisation of AZD-8931-resistant HER-2 positive breast cancer cells.
Authors: Helen Creedon, Morwenna Muir, Larry Hayward, Valerie Brunton
Journal: Cancer Research (2013)

Abstract The introduction of HER-2 directed therapies has revolutionised the management of both early and advanced HER-2 positive breast cancer. However, despite significant improvements in treatment outcomes, both inherent and acquired resistance are frequently encountered problems. Emerging evidence from early phase neo-adjuvant clinical trials, such as Neo-sphere and Neo-ALTTO, suggests that targeting multiple members of the Human epidermal growth factor receptor (HER) family is more efficacious than single target inhibition. AZD 8931 is a novel equipotent reversible tyrosine kinase inhibitor of EGFR, HER-2 and HER-3 signalling with proven pre-clinical efficacy in breast, head and neck and non-small cell lung cancers {1}. To investigate potential mechanisms of acquired resistance to AZD-8931, HER-2 amplified SKBR-3 breast cancer cells were rendered resistant by culture with escalating doses of drug. Resistant and parental cell lines were phenotypically distinct with resistance being associated with greater cell spreading and increased cell density. Cross resistance to lapatinib, a reversible dual EGFR/HER 2 tyrosine kinase inhibitor, was demonstrated with an over 50 fold increase in IC50. Signalling changes associated with a resistant phenotype were explored with a combination of Reverse Phase Protein Array (RPPA) and western blotting. Following drug treatment, resistant cells still displayed a dose-dependent reduction in phospho HER-2 (Tyr 1248)/EGFR (Tyr 1173). However, constitutive activation of the HER 3 pathway resulted in persistent downstream signalling via the PI3K/AKT pathway and increased cell survival. Tumorigenesis in the MMTV-Nic model is driven by mammary-specific expression of a constitutively active HER 2 transgene {2}. This model has been crossed with a strain with a floxed PTEN allele {2} and studies are currently under way to explore the role of PTEN in AZD-8931 resistance. Citation Format: Helen Creedon, Morwenna Muir, Larry Hayward, Valerie Brunton. Development and characterisation of AZD-8931-resistant HER-2 positive breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4453. doi:10.1158/1538-7445.AM2013-4453
Similar arrhythmicity in hypertrophic and fibrotic cardiac cultures caused by distinct substrate-specific mechanisms
Authors: Saïd F.A. Askar, Brian O. Bingen, Martin J. Schalij, Jim Swildens, Douwe E. Atsma, Cindy I. Schutte, Antoine A.F. de Vries, Katja Zeppenfeld, Dirk L. Ypey, Daniël A. Pijnappels
Journal: Cardiovascular Research (2012)

Cardiac hypertrophy and fibrosis are associated with potentially lethal arrhythmias. As these substrates often occur simultaneously in one patient, distinguishing between pro-arrhythmic mechanisms is difficult. This hampers understanding of underlying pro-arrhythmic mechanisms and optimal treatment. This study investigates and compares arrhythmogeneity and underlying pro-arrhythmic mechanisms of either cardiac hypertrophy or fibrosis in in vitro models. Fibrosis was mimicked by free myofibroblast (MFB) proliferation in neonatal rat ventricular monolayers. Cultures with inhibited MFB proliferation were used as control or exposed to phenylephrine to induce hypertrophy. At Day 9, cultures were studied with patch-clamp and optical-mapping techniques and assessed for protein expression. In hypertrophic (n = 111) and fibrotic cultures (n = 107), conduction and repolarization were slowed. Triggered activity was commonly found in these substrates and led to high incidences of spontaneous re-entrant arrhythmias [67.5% hypertrophic, 78.5% fibrotic vs. 2.9% in controls (n = 102)] or focal arrhythmias (39.1, 51.7 vs. 8.8%, respectively). Kv4.3 and Cx43 protein expression levels were decreased in hypertrophy but unaffected in fibrosis. Depolarization of cardiomyocytes (CMCs) was only found in fibrotic cultures (−48 ± 7 vs. −66 ± 7 mV in control, P < 0.001). L-type calcium-channel blockade prevented arrhythmias in hypertrophy, but caused conduction block in fibrosis. Targeting heterocellular coupling by low doses of gap-junction uncouplers prevented arrhythmias by accelerating repolarization only in fibrotic cultures. Cultured hypertrophic or fibrotic myocardial tissues generated similar focal and re-entrant arrhythmias. These models revealed electrical remodelling of CMCs as a pro-arrhythmic mechanism of hypertrophy and MFB-induced depolarization of CMCs as a pro-arrhythmic mechanism of fibrosis. These findings provide novel mechanistic insight into substrate-specific arrhythmicity.
Relation between falciparum malaria and HIV seropositivity in Ndola, Zambia.
Authors: O. O. Simooya, R. M. Mwendapole, S. Siziya, A. F. Fleming
Journal: BMJ (1988)

Women under the age of 20 years constituted a small minority of those attending the colposcopy clinic.This mainly reflects the small number of women of this age group who were screened.During the period of the study 46/1000 smears in girls under the age of 20 years were abnormal (range 41/1000 in 1982 to 69/1000 in 1985), the pick up rate for all ages being 65/1000 during that period (personal communication M Colquhoun, department of cytopathology, University of Edinburgh).This is two to three times the pick up rate reported by Sadeghi.5It is also of interest that in our study over half the patients had evidence of cervical human papillomavirus infection and that 68% of patients with external genital warts also showed cervical intraepithelial neoplasia.Significantly, two thirds of patients with vulval warts and normal findings on cervical cytology had cervical intraepithelial neoplasia, koilocytosis, or both.It is difficult to escape the conclusion that cervical screening may not be detecting all precancerous lesions and that patients with external genital warts should have colposcopic assessment even if their cervical cytology is reported as normal.The discovery of premalignant lesions of the cervix in increasing numbers of teenagers is worrying.While none of our teenagers had invasive disease, 25% of the whole group (31% of those with abnormal cervical cytology) had cervical intraepithelial neoplasia grade III, which supports a policy of especial vigilance in this group and suggests that the onset of cervical screening should start from an earlier age than currently recom- mended.
Immunological Aspects of Rheumatology
Authors: Robert Stephen Katz
Journal: JAMA (1982)

If you have been wondering lately which properties of immune complexes are most important in leading to tissue injury; what are the biological properties of complement (at least 12); and what is known about lymphocyte subpopulations related to the rheumatic diseases, then you should read all or part of<i>Immunological Aspects of Rheumatology</i>. This competent, concise book by 19 British authors brings the reader up to date in rheumatologic immunology. There are fine discussions of the relationship of Epstein-Barr virus to rheumatoid arthritis; the possible connection of viral infections to the etiology of the connective-tissue diseases; immunogenetics; neutrophils, macrophages, and eosinophils; and autoantibodies. This is a gentle book for us rheumatologists who don't know a lot of immunology. It doesn't try to make us appear foolish. It is well written, well documented with references (67 pages), and fairly easy reading. Reading the different chapters in this book is like trying
Neointimal Thickening After Severe Coronary Artery Injury Is Limited by Short-term Administration of a Factor Xa Inhibitor
Authors: Robert S. Schwartz, Daniel J. Holder, David R. Holmes, John P. Veinot, Allan R. Camrud, Michael A. Jorgenson, Robert G. Johnson
Journal: Circulation (1996)

Fibrin- and platelet-rich thrombus formations occur as the initial event after percutaneous transluminal coronary angioplasty. We therefore tested the hypothesis that short-term administration of the recombinant tick anticoagulant peptide (rTAP), a factor Xa inhibitor, would reduce the thickness of neointima at 28 days after injury in a porcine coronary balloon angioplasty model.Continuous intravenous infusion of rTAP (average dose, 194 micrograms . kg-1 . min-1) or placebo (vehicle only) was given to the study pigs for 60 hours. The goal of anticoagulation was to maintain the activated clotting time at 200 seconds. A central venous catheter was inserted 2 days before the procedure. On the day of coronary injury, the animals were administered boluses of rTAP (6.5 mg) and then underwent injury with an oversized metallic coil by standard methods in the right, circumflex, or left anterior descending coronary artery. No significant difference in vascular injury between rTAP and vehicle control was observed after euthanasia at 28 days. Significantly less neointimal thickening occurred in the rTAP-treated animals (thickness, mean +/-SD: 0.30 +/-0.08 mm) compared with the control (0.48 +/- 0.12 mm, P< .001).The specific factor Xa inhibitor rTAP, when given in fully anticoagulant doses for a short duration after coronary artery injury in the porcine model, resulted in a long-term decrease in neointimal thickness. These results implicate thrombin generation in neointimal formation and suggest that administration of a potent antithrombotic for several days immediately after the procedure may influence the long-term outcome of the coronary injury with a decrease in neointimal formation.
Does practice based commissioning avoid the problems of fundholding?
Authors: Ian Greener, Russell Mannion
Journal: BMJ (2006)

rather than classifying it as indeterminate, which we believe would be the correct solution for a substantial number of these reported deaths.There is furthermore the interesting statement regarding the 18 . . .cases for which data were available that 'all of them had high risk factors' and by implication the series contains no example of a repeat classic cot death in a low risk family."Professor Hall's conclusion was that he and others regarded the paper's findings as "seriously misleading" and thought they could have "serious consequences" for child protection.
Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice
Authors: Elena Corradini, Delphine Meynard, Qifang Wu, Shan Chen, Paolo Ventura, Antonello Pietrangelo, Jodie L. Babitt
Journal: Hepatology (2011)

The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is a central regulator of hepcidin expression and systemic iron balance. However, the molecular mechanisms by which iron is sensed to regulate BMP6-SMAD signaling and hepcidin expression are unknown. Here we examined the effects of circulating and tissue iron on Bmp6-Smad pathway activation and hepcidin expression in vivo after acute and chronic enteral iron administration in mice. We demonstrated that both transferrin saturation and liver iron content independently influence hepcidin expression. Although liver iron content is independently positively correlated with hepatic Bmp6 messenger RNA (mRNA) expression and overall activation of the Smad1/5/8 signaling pathway, transferrin saturation activates the downstream Smad1/5/8 signaling cascade, but does not induce Bmp6 mRNA expression in the liver. Hepatic inhibitory Smad7 mRNA expression is increased by both acute and chronic iron administration and mirrors overall activation of the Smad1/5/8 signaling cascade. In contrast to the Smad pathway, the extracellular signal-regulated kinase 1 and 2 (Erk1/2) mitogen-activated protein kinase (Mapk) signaling pathway in the liver is not activated by acute or chronic iron administration in mice.Our data demonstrate that the hepatic Bmp6-Smad signaling pathway is differentially activated by circulating and tissue iron to induce hepcidin expression, whereas the hepatic Erk1/2 signaling pathway is not activated by iron in vivo.
Soluble CD14 is increased in bronchoalveolar lavage of active sarcoidosis and correlates with alveolar macrophage membrane-bound CD14.
Authors: I Striz, L Zheng, Y M Wang, H Pokorná, P C Bauer, U Costabel
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

CD14 is a myeloid differentiation antigen which exists in a membrane-bound (55 kD) and a soluble (48 kD) form. This antigen is a receptor for lipopolysaccharide (LPS) structures and triggers the production of various cytokines. The aim of this study was to evaluate whether in active sarcoidosis, a disease with increased proportions of alveolar macrophages (AM) with CD14 expression in BAL fluid, the soluble form of CD14 (sCD14) is also increased. The sCD14 levels were measured in BAL fluid with an ELISA, and membrane-bound CD14 was determined by an immunoperoxidase assay, in active sarcoidosis (n = 13), inactive sarcoidosis (n = 9), idiopathic pulmonary fibrosis (IPF) (n = 6), and control subjects (n = 8). Higher concentrations of sCD14 were present in BAL fluid of patients with active sarcoidosis (58 +/- 34 ng/ml) than in those with inactive disease (13 +/- 10 ng/ml), patients with IPF (5 +/- 5 ng/ml), or control subjects (10 +/- 8% ng/ml) (p < 0.01). Similarly, the proportions of AM expressing membrane-bound CD14 were increased in active sarcoidosis (91 +/- 6%) compared with inactive sarcoidosis (82 +/- 6%), patients with IPF (76 +/- 13%), and control subjects (79 +/- 9%) (p < .05). In sarcoidosis, a significant correlation was found between the sCD14 concentration in BAL fluid and AM membrane expression of CD14 (r = 0.57, p < 0.01). We conclude that sCD14 is increased in BAL of active sarcoidosis suggesting a potential role for this substance as marker of activity and in the pathogenesis of pulmonary sarcoidosis.
Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy
Authors: Thomas Wisenbaugh, Ivor Katz, Jean Davis, Rafique Essop, John Skoularigis, Shirley Middlemost, Christian Röthlisberger, Daniel Skudicky, Pinhas Sareli
Journal: Journal of the American College of Cardiology (1993)
Immunoreactivity of alpha-melanocyte-stimulating hormone, adrenocorticotrophic hormone and beta-endorphin in cutaneous malignant melanoma and benign melanocytic naevi
Authors: None Nagahama, None Funasaka, None Fernandez-Frez, None Ohashi, None Chakraborty, None Ueda, None Ichihashi
Journal: British Journal of Dermatology (1998)

Journal Article Immunoreactivity of α‐melanocyte‐stimulating hormone, adrenocorticotrophic hormone and β‐endorphin in cutaneous malignant melanoma and benign melanocytic naevi Get access M. Nagahama, M. Nagahama Department of Dermatology, Kobe University School of Medicine, 5–1 Kusunoki‐cho 7‐chome, Chuo‐ku, Kobe 650‐0017, Japan, Search for other works by this author on: Oxford Academic Google Scholar Y. Funasaka, Y. Funasaka Department of Dermatology, Kobe University School of Medicine, 5–1 Kusunoki‐cho 7‐chome, Chuo‐ku, Kobe 650‐0017, Japan, YokoFunasaka E‐mail: funasaka@med.kobe‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar M.L. Fernandez‐Frez, M.L. Fernandez‐Frez Department of Dermatology, Kobe University School of Medicine, 5–1 Kusunoki‐cho 7‐chome, Chuo‐ku, Kobe 650‐0017, Japan, Search for other works by this author on: Oxford Academic Google Scholar A. Ohashi, A. Ohashi Department of Dermatology, Kobe University School of Medicine, 5–1 Kusunoki‐cho 7‐chome, Chuo‐ku, Kobe 650‐0017, Japan, Search for other works by this author on: Oxford Academic Google Scholar A.K. Chakraborty, A.K. Chakraborty Department of Dermatology, Yale University School of Medicine, New Haven, CT, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M. Ueda, M. Ueda Department of Dermatology, Kobe University School of Medicine, 5–1 Kusunoki‐cho 7‐chome, Chuo‐ku, Kobe 650‐0017, Japan, Search for other works by this author on: Oxford Academic Google Scholar M. Ichihashi M. Ichihashi Department of Dermatology, Kobe University School of Medicine, 5–1 Kusunoki‐cho 7‐chome, Chuo‐ku, Kobe 650‐0017, Japan, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 138, Issue 6, 1 June 1998, Pages 981–985, https://doi.org/10.1046/j.1365-2133.1998.02263.x Published: 01 June 1998
Controversies in Surgery II
Authors: David C. Sabiston
Journal: JAMA (1983)

The editors of this superb text have selected a series of controversial issues in the current practice of surgery and have invited authorities on both sides of the question to prepare scholarly essays defending their points of view. Those contributing have been asked (1) to state concisely their positions, (2) to discuss the supporting evidence for their points of view, (3) to indicate gaps in the evidence, (4) to emphasize flaws in the opposing points of view presented by the other author, (5) to provide references (with brief annotation of the most important literature on the subject), and, finally, (6) to answer the specific questions put forth by the editors to address each subject thoroughly. In most of the sections, two or more authorities taking opposing or differing positions have been invited to comment on a subject. In some instances, the subject does not lend itself to this approach, and
Mitochondrial DNA modifies cognition in interaction with the nuclear genome and age in mice
Authors: Pierre L Roubertoux, Frans Sluyter, Michèle Carlier, Brice Marcet, Fatima Maarouf-Veray, Chabane Chérif, Charlotte Marican, Patricia Arrechi, Fabienne Godin, Marc Jamon, Bernard Verrier, Charles Cohen-Salmon
Journal: Nature Genetics (2003)
Effects of an amphoteric surfactant on the skin barrier: an in vivo electro-physiological study
Authors: G. BORRONI, E. BERARDESCA, P. GABBA, R. PERICOLI, P.T. PUGLIESE, M. BELLOSTA, G. RABBIOSI
Journal: British Journal of Dermatology (1986)

Journal Article Effects of an amphoteric surfactant on the skin barrier: an in vivo electro‐physiological study Get access G. BORRONI, G. BORRONI Department of Human and Hereditary Pathology, Section of Dermatology, University of Pavia ‐ IRCCS S. Matteo, Pavia, Italy Dr G.Borroni, Clinica Dermatologica dell'Universitá di Pavia, Policlinico S. Matteo, Piazzale C. Golgi, 27100 Pavia, Italy. Search for other works by this author on: Oxford Academic Google Scholar E. BERARDESCA, E. BERARDESCA Department of Human and Hereditary Pathology, Section of Dermatology, University of Pavia ‐ IRCCS S. Matteo, Pavia, Italy Search for other works by this author on: Oxford Academic Google Scholar P. GABBA, P. GABBA Department of Human and Hereditary Pathology, Section of Dermatology, University of Pavia ‐ IRCCS S. Matteo, Pavia, Italy Search for other works by this author on: Oxford Academic Google Scholar R. PERICOLI, R. PERICOLI Department of Human and Hereditary Pathology, Section of Dermatology, University of Pavia ‐ IRCCS S. Matteo, Pavia, Italy Search for other works by this author on: Oxford Academic Google Scholar P.T. PUGLIESE, P.T. PUGLIESE Xienta Institute, Bernville, PA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M. BELLOSTA, M. BELLOSTA Department of Human and Hereditary Pathology, Section of Dermatology, University of Pavia ‐ IRCCS S. Matteo, Pavia, Italy Search for other works by this author on: Oxford Academic Google Scholar G. RABBIOSI G. RABBIOSI Department of Human and Hereditary Pathology, Section of Dermatology, University of Pavia ‐ IRCCS S. Matteo, Pavia, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s31, 1 August 1986, Pages 138–146, https://doi.org/10.1111/j.1365-2133.1986.tb02125.x Published: 01 August 1986