tbuckley/cabot-search huggingface dataset:
UK consultants fees for private work are amongst highest in world
Authors: M. Gould
Journal: BMJ (2004)

Consultants in the United Kingdom charge the highest fees in major developed nations for private work, a new study shows. But the government's introduction of foreign healthcare providers into the United Kingdom will force them to cut their fees.

Research jointly commissioned by Norwich Union Healthcare and the Financial Times shows that UK surgeons are paid up to 59% more in private fees for the most common procedures than their counterparts in the United States, Australia, Canada, and Germany ( Financial Times 2003 December 29:1).

While the survey results were issued with a warning that they had to be “interpreted with care,” because of the different ways that health care is …
Glucoregulatory endocrine responses to intermittent exercise of different intensities: Plasma changes in a pancreatic [beta ]-cell peptide, amylin
Authors: R.R. Kraemer, E.O. Acevedo, L.B. Synovitz, R.J. Durand, L.G. Johnson, E. Petrella, M.S. Fineman, T. Gimpel, V.D. Castracane
Journal: Metabolism (2002)
THE USE OF ALCOHOL IN MEDICAL PRACTICE
Authors: ROGER I. LEE
Journal: JAMA (1925)

It is an old saying that alcohol is a highly inflammable substance whether you apply a match or a word to it. Nevertheless, from time to time some of us with more courage than caution may well venture to express our views concerning the place of alcohol in therapeutics. Certainly it is to be expected that there will be some differences of opinion. Complete agreement means cessation of inquiry, and mental and scientific stagnation.  The difficulties with regard to a reasonable evaluation of the therapeutic place of alcohol are obvious. There are few of us, indeed, that did not have prejudices with regard to alcohol before we entered the therapeutic field. Then, too, the statistical data with regard to alcohol, whether clinical, experimental, sociological or economic, have been subjected to partisan and emotional interpretation.  In this brief paper there will be no discussion of the sociological or economic aspects. Furthermore,
Abstract 1149: The role of the novel Notch1-Sox9 signaling axis in NSCLC progression and EMT
Authors: Kathleen M. Capaccione, Xuehui Hong, Katherine M. Morgan, Thaddeus D. Allen, Gregory D. Miles, Elke K. Markert, J. Michael Bishop, Sharon R. Pine
Journal: Cancer Research (2014)

Abstract Sox9 plays critical roles in the specification and differentiation of numerous progenitor and differentiated cell types during embryonic and fetal development. Sox9 is overexpressed in 40 - 50% of lung adenocarcinomas and associated with poor prognosis in lung cancer patients. We set out to identify upstream pathways that regulate Sox9 expression in lung cancer, as well as the role of Sox9 in lung adenocarcinoma progression. Several developmental and stem cell pathways are known to induce Sox9 transcription during carcinogenesis, including the TGB-β, Wnt/β-catenin, Sonic Hedgehog, and NF-κB signaling. Sox9 has also been shown to be a transcriptional target of the Notch pathway during mouse development, although the binding sites for Notch within the mouse Sox9 promoter are not conserved in humans. We mined gene expression data from three publicly available datasets and found that Hes1, a known Notch target gene, is co-expressed with Sox9 in lung adenocarcinoma. Furthermore, Sox9 mRNA and protein levels were upregulated over 100-fold as early as 14 days after Notch1 induction in the Notch1-induced mouse model of lung cancer, suggesting that Sox9 overexpression is an early event during lung cancer development. Through a series of in vitro assays, we determined that Sox9 is downstream of Notch1 in lung adenocarcinoma cell lines. By ChIP we determined that Sox9 is a direct target of Notch1 and using luciferase reporter assays, we located the previously unidentified human RBP-Jκ binding site, the principle effector of canonical Notch1 signaling, immediately upstream of the Sox9 transcriptional start site. We also examined TGF-β, a known inducer of epithelial-to-mesenchymal transition (EMT) in lung cancer. We determined that induction of Sox9 expression by Notch1 is independent of TGF-β signaling and that TGF-β and Notch1 cooperate in their regulation of Sox9 expression. Loss of Notch1 expression led to an induced MET phenotype, characterized by decreased cell invasion/migration, MET-like morphological changes, and increased E-cadherin expression, which were rescued by Sox9 overexpression. Our data also demonstrate that Sox9 contributes to Notch1-induced EMT in lung adenocarcinoma. These results establish Sox9 as a key Notch1 target gene mediating Notch1-induced EMT independent of TGF-β, leading to poor survival in lung adenocarcinoma. Citation Format: Kathleen M. Capaccione, Xuehui Hong, Katherine M. Morgan, Thaddeus D. Allen, Gregory D. Miles, Elke K. Markert, J. Michael Bishop, Sharon R. Pine. The role of the novel Notch1-Sox9 signaling axis in NSCLC progression and EMT. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1149. doi:10.1158/1538-7445.AM2014-1149
A Role for Selection in Regulating the Evolutionary Emergence of Disease-Causing and Other Coding CAG Repeats in Humans and Mice
Authors: John M. Hancock, Elizabeth A. Worthey, Mauro F. Santibáñez-Koref
Journal: Molecular Biology and Evolution (2001)

The evolutionary expansion of CAG repeats in human triplet expansion disease genes is intriguing because of their deleterious phenotype. In the past, this expansion has been suggested to reflect a broad genomewide expansion of repeats, which would imply that mutational and evolutionary processes acting on repeats differ between species. Here, we tested this hypothesis by analyzing repeat- and flanking-sequence evolution in 28 repeat-containing genes that had been sequenced in humans and mice and by considering overall lengths and distributions of CAG repeats in the two species. We found no evidence that these repeats were longer in humans than in mice. We also found no evidence for preferential accumulation of CAG repeats in the human genome relative to mice from an analysis of the lengths of repeats identified in sequence databases. We then investigated whether sequence properties, such as base and amino acid composition and base substitution rates, showed any relationship to repeat evolution. We found that repeat-containing genes were enriched in certain amino acids, presumably as the result of selection, but that this did not reflect underlying biases in base composition. We also found that regions near repeats showed higher nonsynonymous substitution rates than the remainder of the gene and lower nonsynonymous rates in genes that contained a repeat in both the human and the mouse. Higher rates of nonsynonymous mutation in the neighborhood of repeats presumably reflect weaker purifying selection acting in these regions of the proteins, while the very low rate of nonsynonymous mutation in proteins containing a CAG repeat in both species presumably reflects a high level of purifying selection. Based on these observations, we propose that the mutational processes giving rise to polyglutamine repeats in human and murine proteins do not differ. Instead, we propose that the evolution of polyglutamine repeats in proteins results from an interplay between mutational processes and selection.
Seasonal variations in house dust mite influence the circadian peak expiratory flow amplitude.
Authors: G G Meijer, D S Postma, S van der Heide, D M de Reus, G H Koëter, R J Roorda, W M van Aalderen
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The aim of the study was to investigate whether seasonal differences in house dust mite (HDM) allergen exposure influence the circadian peak expiratory flow (PEF) amplitude in asthmatic children. Asthmatic children (n = 25) with a solitary allergy to HDM were studied in spring and in autumn. All used inhaled corticosteroids (ICS) regularly. Six days after withdrawal of ICS, PEF amplitude (every 4 h during 24 h, highest-lowest/percentage of mean value) was assessed. HDM allergen (HDMA) in living rooms, bedrooms, and mattresses was collected. HDMA levels were not always highest in autumn. PEF amplitudes in spring and autumn did not correlate with HDMA levels in the same season. However, the seasonal difference in PEF amplitude (autumn value - spring value) correlated positively and significantly with the seasonal difference in HDMA exposure levels from the mattresses (rho = 0.34, p < 0.05). Multivariate analysis showed that the seasonal difference in HDMA exposure in the mattress was the single parameter explaining seasonal difference in PEF amplitudes by 21.0% (p = 0.02). Our cross-sectional study showed a higher PEF amplitude not to be significantly associated with higher HDMA exposure in mattresses in a group of HDM-allergic asthmatic children. However, the change in HDMA exposure over seasons contributed significantly to the change in PEF amplitude after withdrawal of ICS in HDM-allergic asthmatic children.
DISSOCIATION OF CORTICOTROPIN-SUPPRESSING ACTIVITY FROM THE EOSINOPENIC AND HYPERGLYCEMIC ACTIVITIES OF CORTICOSTEROID ANALOGUES*
Authors: John W. Kendall, Grant W. Liddle, Charles F. Federspiel, Jerome Cornfield
Journal: Journal of Clinical Investigation (1963)

SUMMARY Although the ACTH-suppressing, eosinopenic,and hyperglycemic activities of corticosteroids havepreviously been considered to be inseparable,three synthetic cortisol analogues have been foundto exhibit significant degrees of dissociation among these biological activities. These three com- poundswere1) 9a-fluoro-1 lf8,17a-dihydroxy-A1' 4-pregnene-3,20-dione; 2) 9a,21-difluoro-11/8,17a- dihydroxy-A4-pregnene-3,20-dione; and 3) 6a-methyl-9a-fluoro-1 1,3,17-dihydroxy-Al 4-pregnene-3,20-dione-21-mesylate. When compared with9a-fluoro-1 1,3,17a,21-trihydroxy-z1 4-pregnene-3,-20-dione as a biological standard, all three of theabove steroids werefound to be somewhatless ef-fective as ACTH-suppressing agents, but almosttotally ineffective as eosinopenic and hyperglyce-micagents. Thedegree of dissociation of ACTH-suppressing activity from eosinopenic and hyper-glycemic activities became greater as dosage wasincreased and was statistically significant at thehigher dosage levels for each of the three steroids.
Presentation of Study Results: The Authors’ Responsibility
Authors: Igor Burstyn, Brian Lee, Nicole B. Gidaya, Michael Yudell
Journal: Environmental Health Perspectives (2012)

A 343 due to disease misclassification, we (Camargo et al. 2011) concluded that our meta-analysis supports the IARC classification.This illustrates again that meta-analyses are not free from subjective decisions and interpretations.In conclusion, meta-analyses are a quantitative statistical tool that, in some instances may inform causal inference, but they never alleviate the need for critical review of all available data; narrative reviews by an interdisciplinary IARC Working Group may be, in some cases, more informative than a synthetic meta-analysis.Therefore, although a comprehensive review of all original data is required, a comprehensive review of all meta-analysis may not be warranted, particularly when the meta-analyses are outdated or cover only a subset of the original studies.The current "Preamble to the IARC Monographs" (IARC 2006) provides the Working Group with all options to perform quantitative meta-analysis where appropriate and helpful for causal inference.Different approaches have been applied in the history of the IARC Monographs.The Volume 100 series of the IARC Monographs confirmed all Group 1 carcinogens identified during the 40-year history of the monographs, which in turn confirmed that the procedures of the IARC Monographs are robust.With more epidemiological studies becoming available for each agent, additional cancer sites being investigated, and relatively small effect estimates becoming center of the discussion, the need for meta-analyses is likely to increase.
Not all PROMs reflect patients' perspectives
Authors: J. Trujols, M. J. Portella
Journal: BMJ (2013)

Pregnancy is a major life event for all women. However, when a psychiatric disorder is added to or exacerbated by the pregnancy then the problem requires expert knowledge from more than one area of medicine. This paper looks at pregnancy and the relationship with depression, eating disorders, and pathological fear of childbirth or tokophobia. It also examines the outcome for these women and their babies. Mental illness is a serious concern. It is now recognised that death from suicide is the leading cause of maternal death overall. Research in these areas is relatively sparse but an attempt is made to collate what is known.
Evaluation of one-visit endoscopic clinic for patients with dyspepsia.
Authors: A K Beavis, S La Brooy, J J Misiewicz
Journal: BMJ (1979)

An evaluation was made of the feasibility of an instant upper-gastrointestinal endoscopy clinic for patients referred to hospital for the investigation of dyspepsia. A total of 200 patients underwent endoscopy using a small-diameter endoscope with only topical pharyngeal anaesthesia but no premedication or sedation. The procedure was successful in 187 of the patients. Its acceptability was high for both patients and doctors. The average duration of the hospital visit was 45 minutes. Instant endoscopy with a small-diameter endoscope provides a convenient and fast primary diagnostic service for patients with dyspepsia.
Generation and characterization of mice deficient in hepsin, a hepatic transmembrane serine protease.
Authors: Q Wu, D Yu, J Post, M Halks-Miller, J E Sadler, J Morser
Journal: Journal of Clinical Investigation (1998)

Hepsin is a type II transmembrane serine protease highly expressed on the surface of hepatocytes. The physiological function of hepsin is not known, although in vitro studies indicate that hepsin plays a role in the initiation of blood coagulation and in hepatocyte growth. To determine the functional importance of hepsin, we generated hepsin-deficient mice by homologous recombination. Homozygous hepsin-/- mice were viable and fertile, and grew normally. In functional assays including tail bleeding time, plasma clotting times, and tissue factor- or LPS-induced disseminated intravascular coagulation models, no significant difference was found between hepsin-/- and wild-type litter mates. Liver weight and serum concentrations of liver-derived proteins or enzymes were similar in hepsin-/- and wild-type mice. Interestingly, serum concentrations of bone-derived alkaline phosphatase were approximately twofold higher in hepsin-/- mice of both sexes when compared with wild-type litter mates. No obvious abnormalities were found in major organs in hepsin-/- mice in histological examinations. Our results indicate that hepsin is not essential for embryonic development and normal hemostasis. Hepsin-/- mice will help to evaluate the long-term effects of hepsin deficiency in these animals.
Serum 25-hydroxyvitamin D concentration does not correlate with atopic dermatitis severity
Authors: Yvonne E. Chiu, Peter L. Havens, Dawn H. Siegel, Omar Ali, Tao Wang, Kristen E. Holland, Sheila S. Galbraith, Valerie B. Lyon, Beth A. Drolet
Journal: Journal of the American Academy of Dermatology (2013)
Acute myelopathy associated with primary infection with human immunodeficiency virus.
Authors: D W Denning, J Anderson, P Rudge, H Smith
Journal: BMJ (1987)

A 29 year old white homosexual man presented with a two and a half week history of severe sore throat, fever, and extreme fatigue. His symptoms did not respond to antibiotics. He had mild bilateral conjunctivitis, a rash over his chest and back, and enlarged lymph nodes, but examination of the nervous system yielded normal results. He had low total white cell and platelet counts. The results of enzyme linked immunosorbent assay for human immunodeficiency virus (HIV) were equivocal when HIV IgM was detected in serum. Despite treatment with ampicillin his temperature remained high and he developed abnormal neurological signs, including a paraparesis and hyperreflexia of the arms. HIV was isolated from lymphocytes from blood and cerebrospinal fluid. Over the next six weeks the patient improved and was discharged. Two months later abnormal neurological signs persisted in his legs. Although various neurological syndromes associated with seroconversion to HIV have been described, this is probably the first report of a patient with myelopathy at the time of seroconversion.
DIPHOSPHOPYRIDINE NUCLEOTIDASE AS AN EXTRACELLULAR PRODUCT OF STREPTOCOCCAL GROWTH AND ITS POSSIBLE RELATIONSHIP TO LEUKOTOXICITY
Authors: Alan W. Bernheimer, Penelope D. Lazarides, Armine T. Wilson
Journal: The Journal of Experimental Medicine (1957)

Among 170 streptococcal strains, there were encountered 98 that yielded culture supernates which caused splitting of diphosphopyridine nucleotide (DPN). All of the latter belonged to Group A, C, or G. Release of DPNase accompanied the growth of diverse antigenic types of Group A streptococci, and data on the frequency of DPNase-producing strains for certain types are given. In contrast, cultures representing 3 species of yeasts and 42 species of bacteria other than streptococci of the Lancefield groups were examined for the presence of DPNase as an extracellular product of growth, but in none of these was the enzyme detected. Of the Group A streptococci examined, 41 strains had pedigrees suggesting that they were the etiologic agents of acute glomerulonephritis, and 39 of these were found to produce DPNase. There is an association between capacity of streptococi to form DPNase and capacity to kill leukocytes. A possible mechanism of leukotoxicity is suggested.
The Immune Consequences of Thermal Injury
Authors: Martin C. Robson
Journal: JAMA (1981)

The complexity of thermal injury and its pathophysiology have stimulated experts in diverse disciplines to contribute vast amounts of new knowledge during the past ten years. Although there are several books devoted to thermal injuries and their pathophysiology,<i>The Immune Consequences of Thermal Injury</i>, the progeny of a five-day symposium held at Arrowhead, Calif, is specifically oriented toward immune mechanisms. Drs John L. Ninnemann and Jack C. Fisher, through the sponsorship of the American Burn Association, the Plastic Surgery Research Foundation in San Diego, and world-renowned contributors have masterfully organized and assimilated the many new concepts and developments in the field of immunity in the thermally injured. Chapter after chapter, 16 in all, the reader is impressed with the logical sequence, comprehensiveness, and clarity of coverage of these important phenomena in the thermally injured host. Each contributor gives the reader a historical review, presenting the findings and opinions of other
Two Distinct Molecular Mechanisms Underlying Cytarabine Resistance in Human Leukemic Cells
Authors: Jie Cai, Vijaya L. Damaraju, Normand Groulx, Delores Mowles, Yunshan Peng, Morris J. Robins, Carol E. Cass, Philippe Gros
Journal: Cancer Research (2008)

Abstract To understand the mechanism of cellular resistance to the nucleoside analogue cytarabine (1-β-d-arabinofuranosylcytosine, AraC), two resistant derivatives of the human leukemic line CCRF-CEM were obtained by stepwise selection in different concentrations of AraC. CEM/4×AraC cells showed low AraC resistance, whereas CEM/20×AraC cells showed high resistance. Both cell lines showed similar patterns of cross-resistance to multiple cytotoxic nucleoside analogues, with the exception that CEM/20×AraC cells remained sensitive to 5-fluorouridine and 2-deoxy-5-fluorouridine. Both cell lines were sensitive to 5-fluorouracil and to a variety of natural product drugs. Although both CEM/4×AraC and CEM/20×AraC cells displayed reduced intracellular accumulation of [3H]AraC, only CEM/4×AraC cells showed reduced uptake of [3H]uridine, which was used to assess nucleoside transport activities. Genes encoding proteins known to be involved in nucleoside transport, efflux, and metabolism were analyzed for the presence of mutations in the two cell lines. In CEM/4×AraC cells, independent mutations were identified at each allele of human equilibrative nucleoside transporter 1 (hENT1; SLC29A1), one corresponding to a single-nucleotide change in exon 4, the other being a complex intronic mutation disrupting splicing of exon 13. In contrast to CEM/20×AraC cells, CEM/4×AraC cells did not bind the hENT1/SLC29A1 ligand nitrobenzylmercaptopurine ribonucleoside and lacked detectable hENT1/SLC29A1 protein. In CEM/20×AraC cells, independent intronic mutations impairing splicing of exons 2 and 3 were found at each allele of the deoxycytidine kinase gene. These studies point to at least two distinct mechanisms of AraC resistance in leukemic cells. [Cancer Res 2008;68(7):2349–57]
Eosinophilia is associated with a higher mortality rate among patients with autoimmune lymphoproliferative syndrome
Authors: Yae‐Jean Kim, Janet K. Dale, Pierre Noel, Margaret R. Brown, Thomas B. Nutman, Stephen E. Straus, Amy D. Klion
Journal: American Journal of Hematology (2007)

Abstract Autoimmune lymphoproliferative syndrome (ALPS) is a disorder associated with heritable defects in lymphocyte apoptosis that result in chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity. To examine the prevalence, mechanisms, and potential implications of eosinophilia in ALPS, we reviewed data retrospectively from 187 consecutive ALPS patients and their family members studied at the National Institutes of Health. ALPS patients with eosinophilia were compared with ALPS patients without eosinophilia with respect to their clinical and immunologic phenotype. Potential mechanisms for the eosinophilia, including abnormal Fas‐mediated eosinophil apoptosis, increased production of eosinophilopoietic cytokines, and presence of anti‐eosinophilic autoantibodies were also explored in a small number of patients from whom samples were available. Analysis of data from 68 ALPS patients and 119 of their relatives identified a distinct subgroup of patients with prominent and persisting eosinophilia that proved to be associated with increased numbers of peripheral blood leukocytes (PBL) of multiple lineages and a trend towards increased serum IgE levels. Eosinophilic ALPS patients also had a significantly higher risk of death due to infectious complications. Although the specific etiology of the eosinophilia in these patients remains uncertain, it does not appear to be associated with an altered serum cytokine profile, increased survival responsiveness of eosinophils to IL‐5, defective Fas‐mediated eosinophil apoptosis, or anti‐eosinophil antibodies. Eosinophilia defines a distinct subgroup of ALPS patients with increased serum IgE levels, increased numbers of PBL of multiple lineages, and higher mortality from infectious complications. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.