tbuckley/cabot-search huggingface dataset:
Abstract 3180: <i>In vitro</i> tool for discovering oncogenes and tumor suppressor genes in a system's manner.
Authors: Gaye Saginc, Leena Ukil, Xingyi Woo, Francesca Menghi, Denis Bertrand, Charlie Wah Heng Lee, Koichiro Inaki, Edison Tak Bun Liu
Journal: Cancer Research (2013)

Abstract The molecular complexity of cancer still remains as the limiting factor for developing efficient therapies with minimal side effects. However, scientists succeeded in determining common alterations in most human cancer types. Each of these alterations results from disruption of an anti-cancer regulation mechanism and/or activation of cancer-promoting networks by genetic and epigenetic changes. As a consequence, cancer cells become capable of mimicking stem cells’ ability to proliferate indefinitely while maintaining their cellular identity, or to self-renew, which is crucial for any type of stem cell. Indeed, some of the networks which are deregulated in cancer normally regulate self-renewal in stem cells. However, self-renewal is tightly regulated in stem cells, while cancer cells manage to escape the internal and external regulation mechanisms. Hence, cancer cells differ from stem cells by displaying disruptions in feedback mechanism controlling the rate of cell division, aberrant differentiation programs and error-prone replication, so they become invasive and even metastatic. We hypothesize that the stemness regulatory “cassette” that serves limitless replicative potential and undifferentiated state is a measure of cancer virulence and progression. We believe that this gene cassette is established through different mechanisms in each cell type, so it can be separated from invasion and instability in a precise and defined manner. To test our hypotheses, we set up a system reconstruction model consisting of induced pluripotent cells and transformed cells as stem and cancer cell models respectively, and their source of primary mouse embryonic fibroblast cells. From this model system, we created a system's map for transformation using differential expression patterns from whole genome expression arrays. We discovered gene networks that are common between stem and cancer cells, but different from their primary cells of origin. We also found deregulated/activated cassettes which are unique for cancer cells and which are hardwired by genomic rearrangements (copy number and structural variations) identified by DNA paired end tag (DNA-PET) sequencing and single nucleotide variations using RNA sequencing. We are now investigating the role of candidate genes selected from this analysis in cancer and stem cell maintenance through a high content siRNA screening. Citation Format: Gaye Saginc, Leena Ukil, Xingyi Woo, Francesca Menghi, Denis Bertrand, Charlie Wah Heng Lee, Koichiro Inaki, Edison Tak Bun Liu. In vitro tool for discovering oncogenes and tumor suppressor genes in a system's manner. [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 3180. doi:10.1158/1538-7445.AM2013-3180
PRESCRIPTION EXIGENCIES.Read before Section on Materia Medica and Pharmacy, at the Forty-third Annual Meeting of the American Medical Association, held at Detroit, Mich., June, 1892.
Authors: JOSEPH P. REMINGTON
Journal: JAMA (1893)

"Every pilot Can steer the ship in calms; but he performs The skillful part, can manage it in storms." —<i>Sir J. Denharn</i>. The prescription is justly regarded by both professions as the most important link in the chain which binds them together. Upon the insignificant scraps of paper are traced the characters which represent the conclusions reached by the practitioner after most serious consideration of the patient's case and to the earnest physician the writing of the prescription is his most responsible duty. Notwithstanding the exceptions to the rule that are constantly forced to the attention of the pharmacist, safe ground can only be held by assuming that the physician always means what he writes and writes for exactly what he means. But, exigencies arise, we are all fallible, and "errare est humanum" must never be forgotten. Constant vigilance must then be the rule for the apothecary. Yet it must
International issues on human health effects of exposure to chemical mixtures.
Authors: Victor J Feron, Flemming R Cassee, John P Groten, Petronella W van Vliet, Job A van Zorge
Journal: Environmental Health Perspectives (2002)

In this article, we highlight new developments and recent studies concerning adverse human health effects related to chemical mixtures. One group of activities comprises the development of a new computer program for analyzing mixture studies and a mathematical model as a basis for combination rules that predict the toxicity of mixtures. Other new activities in the area of experimental studies are the application of gene expression technologies in mixture research, and pattern recognition as a tool in safety evaluation of complex mixtures. A "bottom-up" approach for chemosensory detection of mixtures has recently been presented. Other topics include a method for the safety evaluation of natural flavoring complexes, and an evaluation of the possible health effects of the simultaneous intake of food additives. Examples of issues related to mixtures of airborne chemicals are potential interaction of fine particles and gaseous pollutants in ambient air, nasal cancer associated with inhaled chemical mixtures, and the recommendation of a limit value for volatile organic compounds. Topics of a more strategic nature include studies concerning the public health effects of large airports, and the development of criteria for a harmonized classification of chemical mixtures. This overview illustrates that strategies to tackle the safety evaluation of combined exposures and complex mixtures as well as models facilitating the interpretation of findings in the context of risk assessment of mixtures have become increasingly important. It is true that exposure of humans to chemical mixtures is the rule rather than the exception, and therefore health risk assessments should focus on mixtures and not on single chemicals. It is also true, however, that humans have learned to cope with exposure to huge numbers of chemicals simultaneously (food, water, air, soil, and consumer products). Therefore, in view of limited resources for toxicological research, the focus in toxicology should be on priority mixtures--priority being determined by (estimated) health risk (= toxicity and exposure).
The diagnosis and management of tinea
Authors: B. Moriarty, R. Hay, R. Morris-Jones
Journal: BMJ (2012)

<h3>Abstract</h3> During inflammatory reactions, the production and release of chemotactic factors guide the recruitment of selective leukocyte subpopulations. HMGB1 and the chemokine CXCL12, both released in the microenvironment, form a heterocomplex, which exclusively acts on the chemokine receptor CXCR4, enhancing cell migration and, in some pathological conditions such as Rheumatoid Arthritis, exacerbating the immune response. An excessive cell influx at the inflammatory site can be diminished by disrupting the heterocomplex. Here, we report the computationally driven identification of a novel peptide (HBP08), which binds HMGB1 with the highest affinity reported so far (K<sub>d</sub> of 0.8 ± 0.1 μM), able to selectively inhibit the activity of the CXCL12/HMGB1 heterocomplex. The identification of this peptide represents an important step towards the development of innovative pharmacological tools for the treatment of severe chronic inflammatory conditions characterized by an uncontrolled immune response.
Germline APC mutation familial adenomatous polyposis in Indian family
Authors: Y. Wallis, F. Macdonald, P.M. Rindl, M. Hulten, C. Mckeown, D.G. Morton, M.R.B. Keighley, R. Fodde, R.V.D. Luijt, P. Meera Khan
Journal: The Lancet (1992)
Pulmonary Tuberculosis and Hypercalcaemia
Authors: ALLAN G. NEED
Journal: Annals of Internal Medicine (1979)

Letters1 October 1979Pulmonary Tuberculosis and HypercalcaemiaALLAN G. NEED, M.B., PATRICK J. PHILLIPS, M.A.ALLAN G. NEED, M.B.Search for more papers by this author, PATRICK J. PHILLIPS, M.A.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-4-652_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Abbasi and associates (1) suggest that hypercalcemia associated with tuberculosis does not occur until 4 weeks after hospitalization and may be related to vitamin D intake. We have found that a disorder of calcium homeostasis is present at admission in many such patients and explain here why it is not usually recognized.We have retrospectively studied 89 patients with culture-positive pulmonary tuberculosis admitted to the Royal Adelaide Hospital over a 2½-year period. Because hypoalbuminemia was present in 32 patients (36%) at admission, we corrected the calcium to the midpoint of the albumin reference range, assuming that 0.025...References1. ABBASI A, CHEMPLAVIL J, FARAH S, MULLER B, and ARNSTEIN A. Hypercalcemia in active pulmonary tuberculosis. Ann Intern Med. 1979;90:324-8. LinkGoogle Scholar2. PAIN R, ROWLAND K, PHILLIPS P, and DUNCAN B. Current "corrected" calcium concept challenged. Br Med J. 1975;4:617-9. CrossrefMedlineGoogle Scholar3. Diagnostic Standards and Classification of Tuberculosis. New York: National Tuberculosis Association; 1969. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ALLAN G. NEED, M.B.; PATRICK J. PHILLIPS, M.A.Affiliations: Institute of Medical and Veterinary Science Adelaide, South Australia 5000 Australia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEndocrine and Metabolic Aspects of TuberculosisEndocrine and Metabolic Aspects of TuberculosisEndocrine and Metabolic Aspects of TuberculosisHypercalcemia in Active Pulmonary TuberculosisM.P. KITROU, M.D., A. PHYTOU-PALLIKARI, M.S.B., S.E. TZANNES, M.D., K. VIRVIDAKIS, M.D., TH.D. MOUNTOKALAKIS, M.D. 1 October 1979Volume 91, Issue 4 Page: 652-653 Keywords Albumins Calcium Hospitalizations Hypercalcemia Vitamin D ePublished: 1 December 2008 Issue Published: 1 October 1979 PDF downloadLoading ...
Olfactory Plays a Key Role in Spatiotemporal Pathogenesis of Cerebral Malaria
Authors: Hong Zhao, Taiki Aoshi, Satoru Kawai, Yuki Mori, Aki Konishi, Muge Ozkan, Yukiko Fujita, Yasunari Haseda, Mikiko Shimizu, Masako Kohyama, Kouji Kobiyama, Kei Eto, Junichi Nabekura, Toshihiro Horii, Tomoko Ishino, Masao Yuda, Hiroaki Hemmi, Tsuneyasu Kaisho, Shizuo Akira, Manabu Kinoshita, Koujiro Tohyama, Yoshichika Yoshioka, Ken J Ishii, Cevayir Coban
Journal: Cell Host & Microbe (2014)
PHYSIOLOGIC IMPACT OF CHRONIC KIDNEY DISEASE ON WHOLE BLOOD CLOT KINETICS AND STRENGTH
Authors: Usman Baber, M. Urooj Zafar, jaime uribarri, Barbara Murphy, Avi Khan, Farzana Akter, Jeffrey Bander, Paul Muntner, Jason C. Kovacic, Jennifer Yu, Kleanthis Theodoropoulos, Roxana Mehran, George Dangas, Annapoorna Kini, Samin Sharma, Valentin Fuster, Juan Badimon
Journal: Journal of the American College of Cardiology (2012)
Patients With Type Ii Autoimmune Hepatitis Express Functionally Intact Cytochrome P–450 Db1 That Is Inhibited by Lkm–1 Autoantibodies In Vitro But Not In Vivo
Authors: Michael Manns, Ulrich Zanger, Guido Gerken, Kevin F. Sullivan, Meyer Karl-H. Zum Büschenfelde, Urs A. Meyer, Michel Eichelbaum
Journal: Hepatology (1990)

Liver–kidney microsomal–1 autoantibodies characterize a subgroup of autoimmune chronic active hepatitis. The liver antigen of liver–kidney microsomal–1 antibodies has been identified as cytochrome P450 db1, a microsomal enzyme catalyzing the oxidative metabolism of more than 20 drugs, including debrisoquine, sparteine and bufuralol. A genetic polymorphism (debrisoquin–sparteine polymorphism) is responsible for the lack of P450 db1 protein in the livers of 5% to 10% of Caucasians, leading to impaired drug metabolism and a distinct poor metabolizer phenotype. We investigated whether liver–kidney microsomal–1 positive autoimmune chronic active hepatitis patients express functionally intact P450 db1 in their livers. In four patients with liver–kidney microsomal–1 positive chronic active hepatitis, but not in five patients with various liver–kidney microsomal–1 negative liver diseases, the presence of circulating liver–kidney microsomal–1 antibodies was confirmed by immunofluorescence, radioimmunoassay and immunoblotting analysis using recombinant P450 db1. Moreover, only sera from liver–kidney microsomal–1 positive autoimmune chronic active hepatitis patients strongly inhibited the enzymatic activity of P450 db1 in human liver microsomes in vitro . Immunoblotting detected 50–kd P450 db1 protein in liver biopsy specimens from all patients. The in vivo function of P450 db1 was investigated by determining the metabolic ratio for sparteine and its 2–dehydro and 5–dehydro metabolites in 12–hr urine samples after oral administration of sparteine sulfate. In vivo P450 db1-mediated drug metabolism was of the extensive metabolizer phenotype and did not differ significantly between liver–kidney microsomal–1 positive (metabolic ratio = 1.15 ± 0.32) and liver–kidney microsomal–1 negative (metabolic ratio = 1.18 ± 0.48) patients. Thus patients with liver–kidney microsomal–1 positive chronic active hepatitis express functionally intact P450 db1 in their livers. However, the activity of this enzyme is not significantly diminished in vivo by circulating liver–kidney microsomal–1 autoantibodies that react with the active site of P450 db1 and inhibit its function in vitro . (Hepatology 1990;12:127-132).
Internal Biliary Fistula After Cholecystectomy
Authors: B. R. MITTAL, M. D. IBRARULLAH, S. S. SIKORA, B. K. DAS
Journal: Clinical Nuclear Medicine (1993)

A 60-year-old-woman presented with fever, mild jaundice, and an external biliary fistula following cholecystectomy. Her hospital course was complicated by worsening general condition, intractable diarrhea, and cessation of bile output from the fistula site. An ultra-sonogram did not reveal any intra-abdominal collection. Hepatobiliary scintigraphy demonstrated a subhepatic bile leak communicating with the hepatic flexure of the colon. On exploration, the hepatic flexure was adherent to the portahepatis forming an inflammatory mass. Limited exploration with external drainage was performed. The patient succumbed to her illness on the 3rd postoperative day.
Gynecology: Essentials of Clinical Practice
Authors: Brian Little
Journal: JAMA (1977)

The third edition of this now classic text is like an old hat with a new ribbon; it is just as comfortable as ever, but its face-lifting reflects the times. The chapters have been revised, and a new chapter on breast disease has been added. The objective, as stated by the author originally and restated with this new edition, is to present a concise yet comprehensive and up-to-date volume covering the fundamentals of clinical gynecology. Although comprehensive and concise are not always consistent, Thomas Green makes the reader completely comfortable as he discusses many of the more complex aspects of the clinical specialty. The sensation, as I read this text, was that the author was at my shoulder taking me through the clinical aspects of the care of gynecological patients. His enthusiasm pervades the entire text and envelopes the reader. I would like all our students to read the first
Vaginal Bleeding in Pregnancy
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1963)

THE obvious goal of therapy in bleeding during pregnancy is to arrest loss of blood before it threatens loss of life. Although the physician may sometimes fall short of this with respect to the fetus, he can hardly be forgiven for losing the mother. The proper treatment is usually self-evident once a correct diagnosis has been made, but accurate diagnostic evaluation must often be postponed at the very juncture when delay can be dangerous, as in late pregnancy when bleeding subsides and the fetus is immature. In other words, proper management is not necessarily synonymous here with immediate therapy.First . . .
Triiodothyronine in Diagnosis
Authors: JOEL I. HAMBURGER
Journal: Annals of Internal Medicine (1973)

Letters, Comments, and Corrections1 January 1973Triiodothyronine in DiagnosisJOEL I. HAMBURGER, M.D.JOEL I. HAMBURGER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-1-156 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Shenkman and associates (1) remind us that an elevated serum triiodothyronine (T3) concentration need not mean hyperthyroidism. Nonsuppressible 24-hour131I uptake may be seen ineuthyroidpatients with autonomously functioning adenomas, multinodular goiter, or Graves's disease. Thus the principal laboratory criteria for the diagnosis of T3toxicosis are not specific for hyperthyroidism. Shenkman's 10 patients seem bona fide, since all have elevated131I uptake values and histories of previous toxicity. Patients in other published cases have had normal uptake values, non-suppressible, to be sure, with diagnosis based chiefly on the elevated serum T3level (2). Since elevated...References1. SHENKMANMITSUMABLUM LTM: Recurrent hyperthyroidism presenting as triiodothyronine toxicosis. Ann Intern Med 77:410-413, 1972 LinkGoogle Scholar2. WAHNERGORMAN HC: Interpretation of serum tri-iodothyronine levels measured by the Sterling technic. N Engl J Med 284:225-230, 1971 CrossrefMedlineGoogle Scholar3. HAMBURGER J: Hyperthyroidism—Concept and Controversy. Springfield, Ill., Charles C Thomas, Publisher, 1972, p. 28 Google Scholar1. SHENKMANMITSUMABLUM LTM: Recurrent hyperthyroidism presenting as triiodothyronine toxicosis. Ann Intern Med 77:410-413, 1972 LinkGoogle Scholar2. SHENKMANMITSUMAHOLLANDER LTC: Modulation of pituitary responsiveness to thyrotropin-releasing hormone by triiodothyronine. J Clin Invest. In press, 1973 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Northland Thyroid Laboratory Northland Medical Building Southfield, Mich. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1973Volume 78, Issue 1Page: 156-157KeywordsAdenomasAttentionHyperthyroidismResearch laboratoriesToxicityTriiodothyronine Issue Published: 1 January 1973 PDF DownloadLoading ...
Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial
Authors: D.Y.M. Leung, J.M. Hanifin, D.M. Pariser, K.A. Barber, R.G. Langley, P.M. Schlievert, B. Abrams, T. Hultsch
Journal: British Journal of Dermatology (2009)

Background Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. Objectives To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. Methods This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2–49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. Results An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. Conclusions In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.
Serum Cortisol, Plasma Free Fatty Acids, and Urinary Catecholamines as Indicators of Complications in Acute Myocardial Infarction
Authors: RAVI PRAKASH, WILLIAM W. PARMLEY, MATIJA HORVAT, H. J. C. SWAN
Journal: Circulation (1972)

Levels of serum cortisol, plasma free fatty acids (FFA), and urinary catecholamines were collected in 31 patients with acute myocardial infarction on the day of admission to the coronary care unit (samples obtained from 15 patients with diseases other than myocardial infarction were considered as controls). These values were correlated with the presence or subsequent development of left ventricular failure, arrhythmias, shock, or death. Sixteen of 17 infarction patients without the above complications had cortisol levels less than 20 µg%; 10 of 12 patients with complications had higher cortisol levels. All of the infarction patients without complications had plasma FFA levels less than 1100 µEq/liter, while six of nine patients with complications had levels of 1100 µEq/liter or higher. Fourteen of 16 patients without complications had urinary catecholamines less than 12.5 µg%, while seven of 10 patients with complications had levels greater than this. Of interest were a few patients without complications on admission, but with elevated cortisol or FFA levels, who developed complications on the following day. The results of the present study suggest that the generalized metabolic stress of acute myocardial infarction results in elevations of cortisol, FFA, and catecholamines as measurable biochemical indicators and/or predictors of the severity of the infarction.