tbuckley/cabot-search huggingface dataset:
Abstract 1421: Inhibition of melanoma growth by activation of Notch pathway in stromal fibroblasts
Authors: Hongwei Shao, Long Cai, Yan Li, Omaida C. Velazquez, Zhao-Jun Liu
Journal: Cancer Research (2010)

Abstract Background. Tumor microenvironment influences tumor initiation and progression. Fibroblasts are major components of tumor stroma and critically involved in regulating tumor growth and angiogenesis through secretion of soluble factors, synthesis of extracellular matrix and direct cell-cell interaction. The Notch pathway regulates a variety of cellular activities. However, it is unknown whether and how manipulation of Notch signaling in stromal fibroblasts affects melanoma growth. Objectives. This study aimed to investigate the effects of Notch-activated stromal fibroblasts on melanoma growth and elucidate the underlying mechanism. Methods. Enforced activation of Notch pathway was achieved by transducing fibroblasts with lentiviral vector encoding activated Notch1 (NIC). The effect of Notch1-activated stromal fibroblasts on melanoma growth was tested by in vitro co-culture and in vivo co-injection approaches. The soluble factor which produced by Notch1-activated fibroblasts was identified by PCR Array and validated by Western blot analysis. Function of the candidate factor in mediating the inhibitory effect of Notch1-activated stromal fibroblasts on melanoma growth was examined through siRNA-mediated blockade approach and tested by in vitro cell co-culture and in vivo tumor xenografting animal models. Results. Notch1-activated fibroblasts significantly inhibited melanoma growth by inducing tumor cell apoptosis and suppressing tumor angiogenesis. The inhibitory effect of NIC-engineered fibroblasts was mediated by up-regulating WISP-1 expression. Elevated WISP-1 suppressed melanoma growth while blockade of WISP-1 liberated the inhibitory effect. Conclusions. Activation of Notch pathway in stromal fibroblasts can suppress melanoma growth, partially through WISP-1. Our study provides a novel approach to target tumor microenvironment through modulating stromal fibroblasts by manipulation of Notch signaling, and highlights WISP-1 as a potential therapeutic target in melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1421.
Innovation in general practice: Author's reply
Authors: N. Bosanquet
Journal: BMJ (1988)

gresses more rapidly in this group is in dispute.Although we are unlikely to find premalignant disease in the sexually active girls under 16, we think that cytological screening is useful to educate them about the need for regular cervical smears.These patients are likely to have many sexual partners, have a high prevalence of sexually trans- mitted diseases (770/o-A J Robinson, unpublished data), and be at high risk of developing cervical intraepithelial neoplasia.
Cardiovascular Morbidity in Relation to Change in Blood Pressure and Serum Cholesterol Levels in Treated Hypertension
Authors: Ola Samuelsson
Journal: JAMA (1987)

The relationship of cardiovascular disease (CVD) to the control of blood pressure (BP) and serum cholesterol levels was studied in 686 treated, middle-aged hypertensive men whose condition was followed up for 12 years. Both mean in-study BP (<i>P</i>&lt;.001) and serum cholesterol levels (<i>P</i>&lt;.001) were better predictors for CVD than the respective entry levels (both not significant) in multivariate analysis. Surprisingly, for mean in-study systolic and diastolic BP there seemed to be a level (approximately 150 and 85 mm Hg, respectively) below which further reduction of BP had no additional benefit from treatment. Analyses of CVD morbidity in relationship to changes in BP and serum cholesterol levels clearly showed that a combined reduction of both risk factors was necessary to achieve a substantial reduction in morbidity. These study findings indicate that (1) it may be unfavorable to reduce BP below a certain level in middle-aged hypertensive men; and (2) other risk factor interventions must be improved to improve the patient's prognosis. (<i>JAMA</i>1987;258:1768-1776)
GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ–mediated molecular connection between innate and adaptive immunity in the lung
Authors: Pierre-Yves Berclaz, Yoko Shibata, Jeffrey A. Whitsett, Bruce C. Trapnell
Journal: Blood (2002)
Abstract 2283: The role of insulin-like growth factor-1 and insulin like growth factor-1 receptor in obesity and oesophageal cancer
Authors: Suzanne L. Doyle, Claire Donohoe, Joanne Lysaght, Fiona Lithander, Graham Pidgeon, John V. Reynolds
Journal: Cancer Research (2010)

Abstract Introduction: The insulin-like growth factor pathway, which is involved in cell proliferation, differentiation and protection against apoptosis, has been implicated in esophageal cancer progression. This study examined the role of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF-1R) as a potential mechanism linking obesity with esophageal cancer. Methods: IGF-1R expression in esophageal squamous cell carcinoma (KYSE, OE21) and adenocarcinoma (OE19, OE33) cell lines was measured by Western analysis and the effect of IGF-1 (0.1 − 1000 ng/ml) on survival of cell lines in relation to their expression of IGF-1R was assessed by MTT assay. Circulating levels of IGF-I were measured in 50 human serum samples by ELISA and immunohistochemistry determined IGF-1R expression in human tumor sections. Results were related to tumor type, BMI and survival. Results: Higher IGF-1R expression was observed in squamous cell carcinoma cell lines, however only adenocarcinoma cell lines showed significantly increased cell survival in response to IGF-1 (p &amp;lt;0.001). Significantly higher circulating levels of IGF-1 were observed in patients with adenocarcinoma (p = 0.02). In resected esophageal tumor sections, no statistical difference between intensity of IGF-1R expression and BMI or survival was observed, however reduced survival was observed in patients with moderate-strong compared to weak-negative IGF-1R expression. Higher intensity IGF-1R staining was observed in the ‘immune cell rich’ leading edge of adenocarcinomas. Conclusion: This study suggests an important role for IGF-1 in esophageal adenocarcinoma cell survival. Novel findings relating to high IGF-1R expression in the leading edge of esophageal adenocarcinoma and possible associations with obesity are also presented. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2283.
Physical activity in epidemiology: moving from questionnaire to objective measurement
Authors: K F Janz
Journal: British Journal of Sports Medicine (2006)

Physical activity can best be measured by a combination of activity monitors, questionnaires, and analytical techniques

Accurately measuring physical activity in epidemiological research is, of course, central to the internal validity of the research. Ultimately, getting this component of the work right is a prerequisite for successfully discerning the relation between activity and health outcomes, for setting efficacious and reasonable guidelines, for discerning causal factors for activity choices, and for intervening to improve activity levels within our communities. However, measuring a behaviour as complex and multifaceted as activity is, at best, challenging. Physical activity epidemiology relies heavily on questionnaire methods, generally to characterise easy to recall structured movement during exercise, sport, and work. Self reporting activity through questionnaires is cognitively difficult for adults and much more so for children, the elderly, and other subgroups. Questionnaires are also prone to various degrees of measurement error depending on the facet of activity queried and the time period considered. Assumed error in self reports is (somewhat) countered with large sample sizes so, despite shortcomings and given the lack of feasible alternatives, the reliance on questionnaires remains the most common assessment technique in epidemiology.1

Recently, the methodological gap between accuracy and …
Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-β
Authors: Sylvia A. Vetrone, Encarnacion Montecino-Rodriguez, Elena Kudryashova, Irina Kramerova, Eric P. Hoffman, Scot D. Liu, M. Carrie Miceli, Melissa J. Spencer
Journal: Journal of Clinical Investigation (2009)

Duchenne muscular dystrophy (DMD) is an X-linked, degenerative muscle disease that is exacerbated by secondary inflammation. Here, we characterized the immunological milieu of dystrophic muscle in mdx mice, a model of DMD, to identify potential therapeutic targets. We identified a specific subpopulation of cells expressing the Vβ8.1/8.2 TCR that is predominant among TCR-β+ T cells. These cells expressed high levels of osteopontin (OPN), a cytokine that promotes immune cell migration and survival. Elevated OPN levels correlated with the dystrophic process, since OPN was substantially elevated in the serum of mdx mice and muscle biopsies after disease onset. Muscle biopsies from individuals with DMD also had elevated OPN levels. To test the role of OPN in mdx muscle, mice lacking both OPN and dystrophin were generated and termed double-mutant mice (DMM mice). Reduced infiltration of NKT-like cells and neutrophils was observed in the muscle of DMM mice, supporting an immunomodulatory role for OPN in mdx muscle. Concomitantly, an increase in CD4+ and FoxP3+ Tregs was also observed in DMM muscle, which also showed reduced levels of TGF-β, a known fibrosis mediator. These inflammatory changes correlated with increased strength and reduced diaphragm and cardiac fibrosis. These studies suggest that OPN may be a promising therapeutic target for reducing inflammation and fibrosis in individuals with DMD.
The Failure of the Laboratory Worker as a Practitioner.
Authors: J. F. Percy.
Journal: JAMA (1904)

has a separate sort of usefulness and must be given a share of the total available time in accordance with local facilities.Nowhere, however, can the best results be achieved unless the advantages of these different methods of instruction are se¬ cured.The ward class is valuable according to the way in which it is conducted.My experience with students at the University of Pennsylvania has been that they learned more of that which it is most important to learn, in ward classes than in clinics, clinical conferences or work in the wards.The ward classes are composed of not more than ten men, and each group is taken to the bedside by an instructor, who usually demon¬ strates but one case during the hour.The instructor reviews this case thoroughly, taking up the history, the symptoms and the physicial examination systematically.The classes are small enough to allow each student to percuss, auscultate, etc.The important advantage of such a class is that it teaches method, and it is method more than a mere collection of facts that should be taught in practical courses.Compare such a class with the large "ward classes" of the English schools and the advantage of the former becomes obvious.The English ward class, as I have seen it conducted, is a class of from 20 to 30 men, who walk through the ward, stopping at one bed after another, to be shown some interesting feature in this or that case.The result of such a plan must be to teach superficiality
Operating on the Mind: The Psychosurgery Conflict
Authors: William D. Weitzel
Journal: JAMA (1976)

The specter of losing our personal identity and individual integrity through the use of a surgical technique accounts for much of the interest in this topic. The editors of this book represent various professional disciplines. In six chapters, they discuss psychosurgery as an extreme prototype of behavior modification, and they highlight a classic example of the politicization of medicine. Psychosurgery is defined as any operation designed to irreversibly injure or destroy brain tissue for the primary purpose of altering the thoughts, emotions, or behavior of a human being. An unknown number of psychosurgical procedures have been performed in this country since 1936. Apparently, the use of this technique peaked in 1949, with about 5,000 cases reported, and sharply decreased thereafter. Long-term follow-up studies are few and inconclusive. It is known that psychosurgery does not "control" behavior but results in decreased, unpleasant, and maladaptive affects. Undesirable side effects include a decrease
Diagnostic Nuclear Medicine
Authors: E. James Potchen
Journal: JAMA (1972)

What is nuclear medicine? This book characterizes the dilemma in defining a discipline. Although well written, the work is a poorly balanced compilation of "wet-tests" and other peripherally related topics. Specific areas are excellent. Dr. Raeside is to be complimented for his section on classical physics, which is an excellent overview of a very broad topic. The same holds true for the section on modern physics, although it is surprising to see a current text on nuclear medicine with only limited mention of isotope generators. There is a concise summary of radionuclide instrumentation, but it is superficial relative to a marked emphasis (some 60 pages) on dose calculations. Similarly, the counting statistics are dealt with nicely, but the appendix is far too complicated for a textbook of this nature. This depth of information will be useful only to full-time practitioners of nuclear medicine, and the rest of the book is
Selective inhibition of NF- B in Kupffer cells: good, but not for everything
Authors: F. Marra
Journal: Gut (2009)

Nuclear factor kappa B (NF-κB) is a highly conserved transcriptional regulator which has evolved to allow the cells to respond to stressful conditions and to devise appropriate defensive strategies.1 Two lines of protection are pivotally coordinated by members of this family, specifically inflammation, including antimicrobial resistance, and inhibition of apoptotic cell death. Although NF-κB is certainly important in many tissues, it has a particular relevance in liver pathophysiology, as indicated by the fact that interference with the “canonical” NF-κB pathway by gene deletion leads to death in utero due to massive hepatocyte apoptosis.2 Because NF-κB is a regulator of both inflammation and hepatocyte survival, the relevance of cellular specificity of hepatic NF-κB activation can be easily anticipated by the fact that the liver possesses the highest number of macrophages compared to any other tissues, and that macrophages decisively contribute to many inflammatory processes. On the other hand, hepatocytes are critically dependent on the integrity of the NF-κB pathway to survive in adverse conditions, such as those that accompany severe inflammation. For these reasons, strategies that could efficiently block NF-κB activation in a cell-specific fashion are extremely appealing, in order to inhibit inflammation while preserving hepatocyte survival.

The study of Hoffmann et al 3 published in this issue of Gut (see page 1670) addresses this important issue, describing the effects of a strategy directed to selectively inhibit NF-κB in Kupffer cells, in different murine models of liver injury. Unlike previous studies, where cell-specific inhibition of NF-κB was obtained generating conditional knock-out mice, the strategy utilised by Hoffmann et al 3 …
Poor immunogenicity of a self/tumor antigen derives from peptide–MHC-I instability and is independent of tolerance
Authors: Zhiya Yu, Marc R. Theoret, Christopher E. Touloukian, Deborah R. Surman, Scott C. Garman, Lionel Feigenbaum, Tiffany K. Baxter, Brian M. Baker, Nicholas P. Restifo
Journal: Journal of Clinical Investigation (2004)

Understanding the mechanisms underlying the poor immunogenicity of human self/tumor antigens is challenging because of experimental limitations in humans. Here, we developed a human-mouse chimeric model that allows us to investigate the roles of the frequency and self-reactivity of antigen-specific T cells in determination of the immunogenicity of an epitope (amino acids 209-217) derived from a human melanoma antigen, gp100. In these transgenic mice, CD8+ T cells express the variable regions of a human T cell receptor (hTCR) specific for an HLA-A*0201-restricted gp100(209-217). Immunization of hTCR-transgenic mice with gp100(209-217) peptide elicited minimal T cell responses, even in mice in which the epitope was knocked out. Conversely, a modified epitope, gp100(209-217(2M)), was significantly more immunogenic. Both biological and physical assays revealed a fast rate of dissociation of the native peptide from the HLA-A*0201 molecule and a considerably slower rate of dissociation of the modified peptide. In vivo, the time allowed for dissociation of peptide-MHC complexes on APCs prior to their exposure to T cells significantly affected the induction of immune responses. These findings indicate that the poor immunogenicity of some self/tumor antigens is due to the instability of the peptide-MHC complex rather than to the continual deletion or tolerization of self-reactive T cells.
THE CHOROID PLEXUS AND PSAMMOMAS: An Emeritus Lecture delivered at the Middlesex Hospital, February 7th, 1922
Authors: J. Bland-Sutton
Journal: BMJ (1922)

THE ruffle-like structures, called choroid plexuses, which float in the ventricular fluid of man's brain, have aroused the curiosity of anatomists for centuries, yet they took little more interest in them than gardeners take in weeds.Of late these plexuses have acquired importance for pathologists and clinicians.THE CHOROID PLEXUS.
The Transition from a Pharmacophore-Guided Approach to a Receptor-Guided Approach in the Design of Potent Protein Kinase C Ligands
Authors: Victor E Marquez, Kassoum Nacro, Samira Benzaria, Jeewoo Lee, Ravij Sharma, Kelly Teng, George W.A Milne, Bruno Bienfait, Shaomeng Wang, Nancy E Lewin, Peter M Blumberg
Journal: Pharmacology & Therapeutics (1999)
SYPHILIS SUCCESSFULLY TREATED BY HYDRIATICS.
Authors: ELMER LEE
Journal: JAMA (1896)

There is, perhaps, no disease whose character is so black, and whose ravages are so universally distressing as that under consideration. The name syphilis strikes terror into the soul of its victim, and measureless encertainty in the mind of the professional attendant upon whose shoulders the responsibility of treatment is placed. The exact origin of syphilis is uncertain. The records do not clearly establish by whom or at what time in the history of the world the disease was first discovered. There has been much discussion concerning this point, but little satisfaction has resulted. It is the common habit of Europeans to associate the disease with the return of the followers of Columbus, in 1493, from their discoveries of the West Indies. However this may be, without the shadow of a doubt, the same disease must have existed centuries before among the races of the Orient. The first record of
Professor Doll failed to declare interests when working on vinyl chloride
Authors: Roger Dobson
Journal: BMJ (2006)

The eminent epidemiologist Richard Doll acted as a paid industrial consultant to several chemical firms around the time he was working on a paper on the possible dangers of exposure to vinyl chloride, a new article says. Professor Doll, who died last year, did not declare that interest, the article claims. 

The authors of the review article, which was published online ahead of print publication on 3 November in the American Journal of Industrial Medicine (www3.interscience.wiley.com, doi: 10.1002/ajim.20357), say that the payments raise questions about whether or not consultancies influenced his work 

The article describes a number of cases of researchers and ties to industry. “The case studies are troublesome, because they involved some of the world's leading epidemiologists,” wrote the authors, from Orebro University, Orebro, Sweden, the Social Policy Research Institute, Skokie, Illinois, and Hebrew University-Hadassah …
Adaptive Evolution of Newly Emerged Micro-RNA Genes in Drosophila
Authors: J. Lu, Y. Fu, S. Kumar, Y. Shen, K. Zeng, A. Xu, R. Carthew, C.-I Wu
Journal: Molecular Biology and Evolution (2008)

How often micro-RNA (miRNA) genes emerged and how fast they evolved soon after their emergence are some of the central questions in the evolution of miRNAs. Because most known miRNA genes are ancient and highly conserved, these questions can be best answered by identifying newly emerged miRNA genes. Among the 78 miRNA genes in Drosophila reported before 2007, only 5 are confirmed to be newly emerged in the genus (although many more can be found in the newly reported data set; e.g., Ruby et al. 2007; Stark et al. 2007; Lu et al. 2008). These new miRNA genes have undergone numerous changes, even in the normally invariant mature sequences. Four of them (the miR-310/311/312/313 cluster, denoted miR-310s) were duplicated from other conserved miRNA genes. The fifth one (miR-303) appears to be a very young gene, originating de novo from a non-miRNA sequence recently. We sequenced these 5 miRNA genes and their neighboring regions from a worldwide collection of Drosophila melanogaster lines. The levels of divergence and polymorphism in these miRNA genes, vis-à-vis those of the neighboring DNA sequences, suggest that these 5 genes are evolving adaptively. Furthermore, the polymorphism pattern of miR-310s in D. melanogaster is indicative of hitchhiking under positive selection. Thus, a large number of adaptive changes over a long period of time may be essential for the evolution of newly emerged miRNA genes.
Association between waiting times and short term mortality and hospital admission after departure from emergency department: population based cohort study from Ontario, Canada
Authors: A. Guttmann, M. J. Schull, M. J. Vermeulen, T. A. Stukel
Journal: BMJ (2011)

<b>Objective</b> To determine whether patients who are not admitted to hospital after attending an emergency department during shifts with long waiting times are at risk for adverse events. <b>Design </b>Population based retrospective cohort study using health administrative databases. <b>Setting </b>High volume emergency departments in Ontario, Canada, fiscal years 2003-7. <b>Participants</b> All emergency department patients who were not admitted (seen and discharged; left without being seen). <b>Outcome measures </b>Risk of adverse events (admission to hospital or death within seven days) adjusted for important characteristics of patients, shift, and hospital. <b>Results</b> 13 934 542 patients were seen and discharged and 617 011 left without being seen. The risk of adverse events increased with the mean length of stay of similar patients in the same shift in the emergency department. For mean length of stay ≥6 <i>v</i> &lt;1 hour the adjusted odds ratio (95% confidence interval) was 1.79 (1.24 to 2.59) for death and 1.95 (1.79 to 2.13) for admission in high acuity patients and 1.71 (1.25 to 2.35) for death and 1.66 (1.56 to 1.76) for admission in low acuity patients). Leaving without being seen was not associated with an increase in adverse events at the level of the patient or by annual rates of the hospital. <b>Conclusions</b> Presenting to an emergency department during shifts with longer waiting times, reflected in longer mean length of stay, is associated with a greater risk in the short term of death and admission to hospital in patients who are well enough to leave the department. Patients who leave without being seen are not at higher risk of short term adverse events.