tbuckley/cabot-search huggingface dataset:
Abstract 78: BRCA1/2 mutation analysis in 43 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation
Authors: Britta Stordal, Kirsten Timms, Mickaël Renaud, Julien Thery, Angela Farelly, Deborah Williams, Jennifer Potter, Thanh Tran, Greg Korpanty, Mattia Cremona, Mark Carey, Jie Li, Yang Li, Ozlem Aslan, John J. O'Leary, Gordon B. Mills, Bryan T. Hennessy
Journal: Cancer Research (2012)

Abstract Introduction: Germline mutations in DNA repair genes BRCA1/2 increase the risk of developing breast and ovarian cancer. Germline BRCA1/2 mutations occur in 8.6-13.7% of unselected epithelial ovarian cancers, somatic mutations are also frequent. BRCA1/2 mutated or dysfunctional cells may be sensitive to PARP inhibition by synthetic lethality, the inhibition of two major DNA repair pathways. Therefore, there is a need to characterize ovarian cell lines for their BRCA1/2 status for in vitro studies of novel drugs. Methods: The BRCA1/2 genes were sequenced in 43 ovarian cell lines, mRNA expression of BRCA1/2 and gene methylation of BRCA1 were also examined. The cytotoxicity of PARP inhibitors olaparib and veliparib was examined in 10 cell lines. Results: Sequencing of BRCA1/2 revealed 18 and 33 different alterations respectively, mostly non-pathogenic polymorphisms. The cell line SNU-251 has a deleterious BRCA1 mutation at 5564G&amp;gt;A and is the only deleterious BRCA1/2 mutant in the panel. Two cell lines (UPN-251 and PEO1) had deleterious mutations as well as additional reversion mutations which restore the function of the protein. BRCA1 was methylated in three cell lines (A1847, OVCAR8, EF021) and there was a corresponding decrease in gene expression in these cell lines. The deleterious mutant SNU-251 was relatively resistant to PARP inhibition, compared to wild-type cells. However, the methylated cell lines A1847 and OVCAR8 were more sensitive to PARP inhibition than wild-type cells. Conclusions: The incidence of BRCA1/2 deleterious mutations 1/43 cell lines (2.3%) is much lower than the population incidence. The reversion mutations suggest that there is a selective pressure against BRCA1/2 mutations in cell culture. PARP inhibitors may be useful in patients with BRCA1 methylation and reduced gene expression in their ovarian tumour. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 78. doi:1538-7445.AM2012-78
TUBERCULIN AS A DIAGNOSTIC TEST OF TUBERCULOSIS IN MAN
Authors: L. M. RYAN
Journal: JAMA (1918)

When one delves into the vast amount of bewildering literature that represents the present day knowledge of tuberculins, one is apt to emerge with a chaotic idea, if any at all, of the entire matter. From this literature I have made selections, and have arranged the matter in the way in which it makes the subject clearest to me. I present it here as it applies to diagnostic tests.  Before taking up the subject matter I will give some definitions of terms used, in accordance with my plan:  Antituberculin.  —A substance found in the blood and tissues (Ludke, 1907) of a tuberculous person after being treated with tuberculin. In this connection this would also be called substance sensabilitrice , antibody or amboceptor.  Antigen.  —The exciting agent—in this case, the injected or applied tuberculin.  Complement.  —A protective substance found in normal blood serum. Its union with the foregoing factors has been found
Interferon in suction blister fluid from psoriatic lesions
Authors: J.R. BJERKE, J.K. LIVDEN, M. DEGRE, R. MATRE
Journal: British Journal of Dermatology (1983)

Interferon (IFN) (at least 16 units/ml) was demonstrated in suction blister fluid obtained from lesional skin in nine of thirteen patients with psoriasis vulgaris and in two patients with allergic contact dermatitis, but not in blister fluid from unaffected skin. IFN was detected in only three of the sera from the patients with psoriasis. The difference in results between the blister fluid and the sera from these patients was statistically significant (P less than 0.025). Evidence was obtained which indicated that the activity was probably IFN-gamma (immune IFN), but the additional presence of IFN-alpha in some of the fluids could not be excluded. The data indicate that IFN is produced locally in the psoriatic lesions, most likely by activated T lymphocytes.
An Accurate, Clinically Practical System For Spatial Vectorcardiography
Authors: ERNEST FRANK
Journal: Circulation (1956)

This paper describes a news improved system of spatial vectorcardiography that is practical for clinical use. It represents an optimum compromise among such factors as soundness of theoretic basis, accuracy, reproducibility, signal-to-noise ratio, and speed of application. Some of its advantages over currently employed systems include a rational physical basis, corrections for torso shape, avoidance of left arm, insensitivity to individual variability of ventricle location, and accuracy comparable to applicability of 3-dimensional torso-model data to the human subject. Detailed description of electrode placement, practical procedures, and useful technics is included.
Opposite effects of tumour necrosis factor-alpha on type I and III collagen gene expression by human dermal fibroblasts in monolayer and three-dimensional cultures
Authors: None Sato, None Ishikawa, None Abe, None Miyachi
Journal: British Journal of Dermatology (1998)

We have recently established a novel fibroblast culture system supplemented with L-ascorbic acid 2-phosphate. The addition of L-ascorbic acid 2-phosphate enables human dermal fibroblasts to organize a three-dimensional dermis-like structure by accumulating collagens and extracellular matrices. The purpose of this study was to examine the effects of tumour necrosis factor-alpha (TNF-alpha) on collagen gene expression by human dermal fibroblasts in this culture system in comparison with monolayer culture. TNF-alpha suppressed the expression of pro alpha 1 (I) and pro alpha 1 (III) collagen mRNA in monolayer culture. In contrast, their expression was elevated in the three-dimensional culture system. TNF-alpha increased the mRNA expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 both in monolayer and three-dimensional culture. These data suggest that responses of human dermal fibroblasts to TNF-alpha are distinct under the different culture conditions. Extracellular matrices may modulate the responsiveness of fibroblasts to TNF-alpha.
Prognostic importance of lower extremity arterial disease in patients undergoing coronary revascularization in the bypass angioplasty revascularization investigation (BARI)
Authors: Karen A Burek, Kim Sutton-Tyrrell, Maria Mori Brooks, Barbara Naydeck, Norma Keller, Mary Ann Sellers, Gary Roubin, Růžena Jandová, Charanjit S Rihal
Journal: Journal of the American College of Cardiology (1999)
[744] ASSESSMENT OF ASYMPTOMATIC LIVER FIBROSIS IN ALCOHOL ABUSER PATIENTS BY TRANSIENT ELASTOGRAPHY (FIBROSCAN)
Authors: E. Nguyen-Khac, B. Robert, M. Brevet, B. Tramier, C. Decrombecque, J.P. Toly, P. Grignon, S. Lion, L. Le Page, D. Chatelain, J.L. Dupas
Journal: Journal of Hepatology (2007)
Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE‐mediated allergy
Authors: D. Bučková, L. I. Hollá, M. Schüller, V. Znojil, J. Vácha
Journal: Allergy (2003)

Background: Immunoglobulin E (IgE)‐mediated allergy belongs to common chronic disorders resulting from an interaction between both genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31.1, a region that is linked to asthma and bronchial hyperresponsiveness. Recently, several polymorphisms in the promoter region of this gene have been associated with atopic phenotypes in various populations. Methods: We investigated relationship among atopic phenotypes and two polymorphisms [C(‐159)T and G(‐1359)T] in the promoter of the CD14 gene in the Czech population. Polymerase chain reaction with restriction fragment length polymorphism analyses was used to determine the CD14 genotypes in subjects with IgE‐mediated allergic diseases ( n = 562) and random controls ( n = 320). Results: The CD14 allele or genotype distributions were similar in patients and control group. However, the frequency of the C allele of the C(‐159)T polymorphism was higher in patients with positive skin prick tests for moulds than in patients without reactivity to this antigen ( P &lt; 0.002, P corr &lt;0.01). In addition, we found that patients with homozygous genotype (GG) of the G(‐1359)T polymorphism had marginally lower percentage of positive skin prick tests compared with the other genotypes ( P &lt; 0.029, P corr &gt; 0.05). Conclusions: Our study supports the idea that CD14 gene variants may act as disease modifiers of IgE‐mediated allergic diseases.
THE FUTURE OF OTOLARYNGOLOGY
Authors: Joseph Shanks
Journal: JAMA (1952)

To the Editor:—   editorial entitled The Future of Otolaryngology, which appeared in the April 26 issue ofThe Journal, page 1508, was a true summary of the information now available in connection with otolaryngological practice today. However, more should have been said about meeting the challenge in spite of gloomy forecasts by some and bright predictions by others. It should be emphasized strongly that there always was, to a certain extent, the medical otolaryngologist whose chief interest lay in local rhinological and otological diseases (now allergic, psychosomatic, and dermatological) and the surgical otolaryngologist who quickly took up plastic surgery, bronchoesophagology, laryngoscopy, and even gastroscopy. Some mastered fenestrations, laryngeal surgery, neck dissection, esophageal surgery, and thyroid and cancer surgery; some also mastered ophthalmology and diseases of the chest.  Some of those who still practice the conventional field of otolaryngology, especially in smaller communities, call the surgeons super-specialists, overlooking the greater
Gynecologic Procedures and Women's Health
Authors: Nita Walker
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes18 July 2000Gynecologic Procedures and Women's HealthNita Walker, MDNita Walker, MDUniversity of Cincinnati Medical Center, Cincinnati, Ohio. (Walker)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-2-200007180-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Wigton RS, Tape TG, eds. St. Louis: Mosby; 1999. Single-user price, $99.00. ISBN 1556645481. Order phone 800-426-4545.Field of medicine: General internal medicine.Format: CD-ROM software.Minimum system requirements: PC: Windows 3.1, 95, 98, or NT, 133-MHz Pentium with 16 Mb of RAM, 10 Mb of free hard disk space, a 4× CD-ROM drive, sound card, and a video card capable of 800 × 600 resolution. Macintosh: System 7.1, 80-MHz Power Mac with 10 Mb of free hard disk space, 800 × 600 resolution monitor, QuickTime plug-in (available with the program), and a 4× CD-ROM drive.Audience: Primary care physicians.... Author, Article, and Disclosure InformationAffiliations: University of Cincinnati Medical Center, Cincinnati, Ohio. (Walker) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 July 2000Volume 133, Issue 2Page: 160KeywordsBiopsyMedical educationObstetrics and gynecologyPrimary care physiciansSoftware tools ePublished: 15 August 2000 Issue Published: 18 July 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
MYC Activates Stem-like Cell Potential in Hepatocarcinoma by a p53-Dependent Mechanism
Authors: Hirofumi Akita, Jens U. Marquardt, Marian E. Durkin, Mitsuteru Kitade, Daekwan Seo, Elizabeth A. Conner, Jesper B. Andersen, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Cancer Research (2014)

Activation of c-MYC is an oncogenic hallmark of many cancers, including liver cancer, and is associated with a variety of adverse prognostic characteristics. Despite a causative role during malignant transformation and progression in hepatocarcinogenesis, consequences of c-MYC activation for the biology of hepatic cancer stem cells (CSC) are undefined. Here, distinct levels of c-MYC overexpression were established by using two dose-dependent tetracycline-inducible systems in four hepatoma cell lines with different p53 mutational status. The CSCs were evaluated using side population (SP) approach as well as standard in vitro and in vivo assays. Functional repression of p53 was achieved by lentiviral shRNA transduction. The results show that c-MYC expression levels have a differential impact on liver CSC characteristics. At low levels, c-MYC activation led to increased proliferation and enhanced CSC properties including activation of reprogramming transcription factors and CSC marker expression (e.g., NANOG, OCT4, and EpCAM), expansion of SP, and acceleration of tumor growth upon subcutaneous transplantation into immunocompromised mice. However, when exceeding a threshold level, c-MYC induced a proapoptotic program and loss of CSC potential both in vitro and in vivo. Mechanistically, c-MYC-induced self-renewal capacity of liver cancer cells was exerted in a p53-dependent manner. Low c-MYC activation increased spheroid formation in p53-deficient tumor cells, whereas p53-dependent effects were blunted in the absence of c-MYC overexpression. Together, our results confirm the role of c-MYC as a master regulator during hepatocarcinogenesis and establish a new gatekeeper role for p53 in repressing c-MYC-induced CSC phenotype in liver cancer cells.
Abstract 1309: Identification of aurora kinase a as an unfavorable prognostic factor and potential treatment target for metastatic gastrointestinal stromal tumors
Authors: Chun-Nan Yeh, Chueh-Chuan Yen, Yeng-Yang Chen, Chi-Tung Cheng, Shih-Chiang Huang, Ting-Wei Chang, Fang-Yi Yao, Yung-Chan Lin, Yao-Shan Wen, Kun-Chun Chiang, Jen-Shi Chen, Ta-Sen Yeh, Cheng-Hwai Tzeng, Ta-Chung Chao, Jonathan A. Fletcher
Journal: Cancer Research (2014)

Abstract Purpose: Although imatinib mesylate (IM) has revolutionized the management of gastrointestinal stromal tumors (GISTs), drug resistance remains a challenge. Previous studies have shown that the expression of aurora kinase A (AURKA) predicts recurrence in patients with primary surgically-resected GISTs. The current study aims to evaluate the significance of AURKA as an unfavorable prognostic marker for advanced GISTs, and provides evidence that AURKA could be a potential treatment target of GISTs. Experimental Design: The prognostic significance of AURKA, along with other clinicopathological factors, was analyzed in a cohort of 99 IM-treated patients with advanced GISTs using immunohistochemistry. The potential use of an AURKA inhibitor as therapeutic agent against GISTs was also tested in GIST cell lines. Results: Among 99 enrolled patients, poor performance status, large tumor size, drug response, and AURKA overexpression were independent poor prognostic factors for progression-free survival (PFS). For overall survival (OS), only large tumor size and AURKA overexpression were identified as independent unfavorable factors. In an in vitro study, MLN8237, an AURKA inhibitor, was demonstrated to inhibit growth of both IM-sensitive and IM-resistant GIST cells in a concentration-dependent manner. The inhibitory effect of MLN8237 on GIST cells could be attributed to the induction of G2/M arrest, apoptosis, and senescence, possibly through up-regulation of pro-apoptotic proteins. Conclusions: Our study showed that AURAK is an independent poor prognostic factor for both PFS and OS in patients with advanced GISTs treated with IM. AURKA inhibitor could be used as therapeutic agent for both IM-sensitive and IM-resistant GISTs. Citation Format: Chun-Nan Yeh, Chueh-Chuan Yen, Yeng-Yang Chen, Chi-Tung Cheng, Shih-Chiang Huang, Ting-Wei Chang, Fang-Yi Yao, Yung-Chan Lin, Yao-Shan Wen, Kun-Chun Chiang, Jen-Shi Chen, Ta-Sen Yeh, Cheng-Hwai Tzeng, Ta-Chung Chao, Jonathan A. Fletcher. Identification of aurora kinase a as an unfavorable prognostic factor and potential treatment target for metastatic gastrointestinal stromal tumors. [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 1309. doi:10.1158/1538-7445.AM2014-1309
Proteoglycans: the "Teflon" of the airways?
Authors: C P Page
Journal: Thorax (1997)

Proteoglycans are a family of structurally distinct, polyanionic complex carbohydrates composed of repeating disaccharide units. Proteoglycans include heparin, heparan sulphate, chondroitin 4-sulphate, chondroitin 6-sulphate, dermatan sulphate, and hyaluronic acid. Heparin is found in the granules of a subset of mast cells where it is bound to various mediators including histamine. Heparan sulphate has a much wider distribution in the body, being associated with stromal matrices, basement membrane and many cell surfaces, particularly the surface of endothelial cells. Heparin is an anticoagulant, but it is now very apparent that it possesses many other biological activities that have relevance to our understanding of lung diseases, particularly inflammatory diseases of the airway. Recent evidence suggests in the airway when administered by inhalation that could be exploited therapeutically.
Use clinical tests to diagnose asthma and to avoid overdiagnosis, says NICE
Authors: J. Wise
Journal: BMJ (2015)

Doctors should use clinical tests to accurately diagnose asthma rather than simply taking a medical history, the National Institute for Health and Care Excellence (NICE) has said, because around 1.2 million UK adults may be wrongly receiving treatment for the condition.

No gold standard test is currently available to diagnose asthma, and in current practice doctors mainly check for signs and symptoms. But NICE said that almost a third of people being treated for asthma do not have clear evidence of the condition. Some may have had asthma in the past, NICE added, but …
Involvement of urban living environments in atopy and enhanced eosinophil activity: potential risk factors of airway allergic symptoms
Authors: Y. Kuwahara, J. Kondoh, E. Azuma, T. Nakajima, M. Hashimoto, K. Tatara, Y. Komachi
Journal: Allergy (2001)

Background: Airway allergic diseases, such as bronchial asthma and allergic rhinitis, have increased, especially in urban areas. These diseases are characterized by airway inflammation with enhanced eosinophil activity, and the risk of disease development has been shown to increase with the prevalence of atopy. Methods: Questionnaires were administered to 426 healthy adult women aged 30–74 years, living in an urban area of Osaka, Japan, to survey individual living environments and airway allergic symptoms such as cough, sputum, and wheezing. Moreover, serum house‐dust‐mite ( Dermatophagoides pteronyssinus , [Der p])‐specific immunoglobulin E (IgE) and serum eosinophil cationic protein (ECP) were examined by radioimmunoassay, and the atopic status (atopic sensitization) and enhanced eosinophil activity were assessed as Der p‐specific IgE RAST scores of 2–6 and ECP levels of more than 10 ng/ml, respectively. Results: Intensive use of electric air conditioners in hot weather (odds ratio: 2.07 [95% CI: 1.11–3.87]) and mold proliferation in the kitchen (2.77 [1.34–5.73]) significantly increased the risk of atopic sensitization. Poor home ventilation and family smoking appeared to be positively but not significantly associated with atopic sensitization. Personal smoking and intensive use of the air conditioner appeared to be positively related to enhanced eosinophil activity. Atopic status showed significant involvement in the development of wheezing, and the development of cough was significantly associated with enhanced eosinophil activity. Conclusions: The results suggest that some urban styles of living are involved in atopic sensitization and enhanced eosinophil activity in the Japanese urban population, probably due to living conditions, such as indoor dampness and poor home ventilation, caused by tight insulation, which increase exposure to indoor air pollutants, such as respirable mite allergens and tobacco smoke.
Strongyloides stercoralis infection in Burma Star veterans.
Authors: G V Gill, D R Bell
Journal: BMJ (1987)

Cette strongyloidiase est frequente chez les anciens combattants ayant sejourne en Birmanie pendant la IIeme guerre mondiale. Elle persiste longtemps par auto-injection. 80% environ des malades presentent une eruption caracteristique. On estime qu'il doit exister actuellement 100 a 200 cas non diagnostiques
New method for measuring compliance with long term oxygen treatment
Authors: G D Philips, N K Harrison, A R C Cummin, J Ward, V S Shenoy, V Newey, R Ritchie, I P Williams, F J C Millard
Journal: BMJ (1994)

mineral density in the women with distal forearm fractures was lower after correction for age and weight than that in the population based controls (mean Z score -0 46 (95% confidence interval of the difference -0-63 to -0 29)).Bone mineral density in younger women with distal forearm fractures was lower than that in older women (ages 50 to 59, mean Z score -0-72 (-1-0 to -0-45); ages 60 to 69, -0-48 (-0-78 to -0d19); ages ,>70, -0 11 (-0-41 to 0 9)).The figure shows the relation between bone mineral density and age in women with distal forearm fractures and the population based group.The intercepts (P= 0-001) and slopes (P=0 006) of the regression lines were different.1.8 1.6 0 0 0 0 E 000 .4 0 0 0 0 C8 0 0 0 000 0 1 54-.0 0 07 0 08 0 Reato 0.8 ee bone0 minerlodenityo luba spin 0ngei p a0b c 0 P<0 00 0 0 0 0. 0.6 0 ~~~~~~~~0 0 0 0. 0 0 70 80 90Age (years) Relation between bone mineral density of lumbar spine and age in women with fractures of distal forearm (U, ---.; r=0O04, NS) and population based controls (O, -;-r=-0O24, P<OOOO1)
Glucose Measurements and Clinical Correlations
Authors: Daniel C. Niejadlik
Journal: JAMA (1973)

Various methods for glucose analysis of whole blood and plasma are currently utilized and the clinician should be familiar with them when interpreting a glucose value. Three methods of glucose analysis of whole blood and plasma have been evaluated: Somogyi-Nelson, hexokinase, and copper reduction. Linear regression equations were derived and statistical evaluation by analysis of variance revealed highly significant results. Plasma glucose as measured by the copper reduction technique is approximately 17% higher than whole blood glucose measured by the Somogyi-Nelson method. A consistent 5-mg/deciliter difference in plasma glucose was present between the two plasma glucose procedures, the enzymatic method, and the copper reduction method.