tbuckley/cabot-search huggingface dataset:
Abstract 2292: Epigenetic alterations in Barrett's esophagus and esophageal adenocarcinoma: identification and evaluation of potential biomarkers
Authors: Rachele M. Stockdale, Andrew M. Kaz, Shelli M. Morris, Amitabh Chak, Joseph Willis, Dean Brenner, Sharmila Anandabapasathy, Maria Westerhoff, Chao-Jen Wong, Jill Barnholtz-Sloan, Yanwen Chen, William M. Grady
Journal: Cancer Research (2014)

Abstract Patients diagnosed with esophageal adenocarcinoma (EAC) have poor long-term survival rates. Currently, patients identified with Barrett's esophagus (BE), the strongest risk factor for EAC, are placed in costly and invasive surveillance programs. The impact of these surveillance programs on decreasing EAC related mortality is debatable, presumably because many patients with BE are not diagnosed until they develop cancer and because of suboptimal BE risk markers for EAC. Thus, there is a need for more accurate biomarkers. Epigenetic alterations in BE have the potential to be detection and risk markers for BE and EAC. In order to identify individual gene methylation patterns of normal squamous (SQ) epithelium, BE, low-grade dysplasia, high-grade dysplasia and EAC tissues, we have conducted genome-wide methylation assessments of these tissue types using HumanMethylation450 arrays (Illumina). Unique methylation signatures for each histological subtype have been identified by unsupervised clustering. Additionally, we determined the mean methylation state (‘beta value’) for more than 480,000 CpGs for each sample group. After normalization and filtering, differentially methylated loci (FDR p &amp;lt; 0.05) with mean beta values with differences greater than 0.20 between the different tissue types were used to identify potential biomarkers. These biomarkers were then subjected to technical and clinical validation studies. We have currently identified and validated four potential biomarkers that may be useful in detection assays for BE and EAC. We have found two CpGs that distinguish EAC from BE, and two other CpGs that distinguish BE from SQ epithelium. The best performing biomarker has 100% sensitivity and 87.5% specificity in its ability to distinguish BE from EAC in the validation set of tissue samples. We presently have a number of additional candidates in various stages of validation. In summary, we have shown that differential methylation patterns exist between the various stages of progression from normal SQ epithelium to BE and ultimately EAC. Furthermore, some of these methylated CpGs have potential to be used as detection markers for BE or EAC. Citation Format: Rachele M. Stockdale, Andrew M. Kaz, Shelli M. Morris, Amitabh Chak, Joseph Willis, Dean Brenner, Sharmila Anandabapasathy, Maria Westerhoff, Chao-Jen Wong, Jill Barnholtz-Sloan, Yanwen Chen, William M. Grady. Epigenetic alterations in Barrett's esophagus and esophageal adenocarcinoma: identification and evaluation of potential biomarkers. [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 2292. doi:10.1158/1538-7445.AM2014-2292
The Musculoskeletal System
Authors: James L. Hughes
Journal: JAMA (1976)

This text concerns itself with the structure and function of the musculoskeletal system and directs the basic information toward the proper diagnosis and treatment. The book takes up the gross anatomy of the limbs and back, as well as the individual tissues of the musculoskeletal system—bone, muscle, cartilage, and synovium. Included are the microscopic structure, physiology, biochemistry, and pathology. The excellent text gives well-written, concise information. The beginning of each section indicates the goals and objectives that allow the reader to assess his individual learning progress to the maximum degree of efficiency and at an individual pace. Information flows smoothly from section to section, with no break in continuity. The text is more than adequate to give the reader a concrete basis on which to build a stable foundation for future knowledge. The selected references for the most part are represented by textbooks on a given topic. Areas of special
Uric acid concentration as a risk marker for blood pressure progression and incident hypertension: A Chinese cohort study
Authors: Tsan Yang, Chi-Hong Chu, Chyi-Huey Bai, San-Lin You, Yu-Ching Chou, Lee-Ching Hwang, Kuo-Liong Chien, Ta-Chen Su, Chin-Hsiao Tseng, Chien-An Sun
Journal: Metabolism (2012)
The Toxicity and Dose of Desipramine Hydrochloride
Authors: Y. Amitai, H. Frischer
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Desipramine hydrochloride has been associated with a disproportionately high fatality rate. The relative risk of death from desipramine in suicide attempt is twofold to threefold higher than that of other tricyclic antidepressants.<sup>1,2</sup>Sudden deaths have occurred in three children treated with desipramine for attention deficit disorder (<i>Med Lett</i>. June 1,1990). Outcome data from overdoses with four tricyclic antidepressants for the years 1989 through 1992 (Table) show a significantly higher fatality rate from desipramine (<i>P</i>&lt;.001). The increased relative toxicity of desipramine requires explanation. The pharmacokinetic data of four tricyclic antidepressants listed in the Table show a key difference between tertiary and secondary amines. The secondary amines desipramine and nortriptyline hydrochloride have higher distribution volumes, red blood cell (RBC)/plasma ratios, and a higher proportion of unbound (free) drug than their respective parent compounds, imipramine hydrochloride and amitriptyline hydrochloride. This distribution pattern implies that desipramine and nortriptyline have
INTRACORONARY BOLUS ADMINISTRATION OF NEOSYNEPHRINE DURING CORONARY INTERVENTION. IMMEDIATE AND THREE-YEAR RESULT
Authors: Walid Sayed M. Hassan, Shabir Shah, Nathem Akhras, Hani Al Sergani, Fawaz Al Turki, Suliman Kharabsheh, Mohamed Shalaby, Ahmed Ahmed
Journal: Journal of the American College of Cardiology (2011)
Atom bombs and genetic damage.
Authors: R J Berry
Journal: BMJ (1982)

Atom bombs and genetic damageThe genetic effects of ionising radiation much more difficult to measure than the somatic.radiation induces mutation, but a cynic could only inescapable evidence for radiation-induced man comes by extrapolation from studies mice.Some studies in medically exposed reported, but by far the greatest effort searching for genetic effects in the offspring of the in Hiroshima and Nagasaki, directed by Schull the auspices of the Atomic Bomb Casualty (since 1975) the Radiation Effects Research began as a straightforward epidemiological study with other probes (growth rates, cytogenetic, chemical) added as techniques became available.the total data has just been published.'In common with virtually every other Hiroshima and Nagasaki results fail to identify mutational effects of radiation.In their early and Schull claimed that there was a change the children of irradiated people which could the induction of deleterious mutations.abandoned this belief.2Previous work also ence between the children of irradiated non-irradiated parents in growth rates, stillbirths, or perinatal new review adds to the observed effects chromosome aneuploidies and 15 balanced autosome changes children (aged 13 years and upward when and one probable mutation in 300 000 electrophoresis (exposed to an estimated locusrem).The firmest conclusion from all this labour unduly sensitive to genetic damage.result in itself.But can anything more all-but-negative studies ?In an earlier phase Nagasaki study, the "minimal" doubling induced mutation-that is, the amount received which produces the same number of occurring spontaneously-was estimated3 "of of 100 r."In their new review, Schull and colleagues' calculate that the doubling dose for human chronic rens.This is appreciably higher than the experimental studies used by the International Radiological Protection to calculate genetic energy transfer, low dose-rate exposures,4 which basis for the commission's recommendations tion.5It is also the figure adopted by Scientific Committee on the Effects Atomic its 1972 and 1977 reports.Estimates of the doubling dose have, continuing tendency for upward revisions.MedicalCouncil committee which reported in 19566 arguments still underlie the assessment stated that "the values for the doubling may be, in general, in the range of individual may reasonably accept a total no t more than 0 r frro onception to theage 30 ye ars addition to that received from the natural background."
Pre-operative liver enzyme predicts survival and recurrence after liver resection for hepatocellular carcinoma arising from non-cirrhotic/non-fibrotic liver: A European perspective
Authors: C.Y. Tan, V.S. Yip, G. Sarno, S. Staettner, M. Terlizzo, N. Misra, S. Fenwick, H. Malik, P. Ghaneh, G. Poston
Journal: International Journal of Surgery (2013)
Imaging Tri-Fusion Multimodality Reporter Gene Expression in Living Subjects
Authors: Pritha Ray, Abhijit De, Jung-Jun Min, Roger Y. Tsien, Sanjiv S. Gambhir
Journal: Cancer Research (2004)

Imaging reporter gene expression in living subjects with various imaging modalities is a rapidly accelerating area of research. Applications of these technologies to cancer research, gene therapy, and transgenic models are rapidly expanding. We report construction and testing of several triple fusion reporter genes compatible with bioluminescence, fluorescence and positron emission tomography (PET) imaging. A triple fusion reporter vector harboring a bioluminescence synthetic Renilla luciferase (hrl) reporter gene, a reporter gene encoding the monomeric red fluorescence protein (mrfp1), and a mutant herpes simplex virus type 1 sr39 thymidine kinase [HSV1-truncated sr39tk (ttk); a PET reporter gene] was found to preserve the most activity for each protein component and was therefore investigated in detail. After validating the activities of all three proteins encoded by the fusion gene in cell culture, we imaged living mice bearing 293T cells transiently expressing the hrl-mrfp-ttk vector by microPET and using a highly sensitive cooled charge-coupled device camera compatible with both bioluminescence and fluorescence imaging. A lentiviral vector carrying the triple fusion reporter gene was constructed and used to isolate stable expressers by fluorescence-activated cell sorting. These stable 293T cells were further used to show good correlation (R(2) approximately 0.74-0.85) of signal from each component by imaging tumor xenografts in living mice with all three modalities. Furthermore, metastases of a human melanoma cell line (A375M) stably expressing the triple fusion were imaged by microPET and optical technologies over a 40-50-day time period in living mice. Imaging of reporter gene expression from single cells to living animals with the help of a single tri-fusion reporter gene will have the potential to accelerate translational cancer research.
Impact of the Methotrexate Administration Dose on the Need for Intrathecal Treatment in Children and Adolescents With Anaplastic Large-Cell Lymphoma: Results of a Randomized Trial of the EICNHL Group
Authors: Laurence Brugières, Marie-Cécile Le Deley, Angelo Rosolen, Denise Williams, Keizo Horibe, Grazyna Wrobel, Georg Mann, Jozsef Zsiros, Anne Uyttebroeck, Ildiko Marky, Laurence Lamant, Alfred Reiter
Journal: Journal of Clinical Oncology (2009)

To compare the efficacy and safety of two methotrexate doses and administration schedules in children with anaplastic large-cell lymphoma (ALCL).This randomized trial for children with ALCL was based on the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Muenster 90 (NHL-BFM90) study protocol and compared six courses of methotrexate 1 g/m2 over 24 hours and an intrathecal injection (IT) followed by folinic acid rescue at 42 hours (MTX1 arm) with six courses of methotrexate 3 g/m2 over 3 hours followed by folinic acid rescue at 24 hours without IT (MTX3 arm). This trial involved most European pediatric/lymphoma study groups and a Japanese group.Overall, 352 patients (96% ALK positive) were recruited between 1999 and 2005; 175 were randomly assigned to the MTX1 arm, and 177 were assigned to the MTX3 arm. Ninety-two percent of patients received protocol treatment. Median follow-up time is 3.7 years. Event-free survival (EFS) curves were superimposed with 2-year EFS rates (73.6% and 74.5% in the MTX1 and MTX3 arms, respectively; hazard ratio = 0.98; 91.76% CI, 0.69 to 1.38). Two-year overall survival rates were 90.1% and 94.9% in MTX1 and MTX3, respectively. Only two CNS relapses occurred (both in the MTX1 arm). Toxicity was assessed after 2,050 courses and included grade 4 hematologic toxicity after 79% and 64% of MTX1 and MTX3 courses, respectively (P < .0001); infection after 50% and 32% of courses, respectively (P < .0001); and grade 3 to 4 stomatitis after 21% and 6% of courses, respectively (P < .0001).The results of the NHL-BFM90 study were reproduced in this large international trial. The methotrexate schedule of the NHL-BFM90 protocol including IT therapy can be safely replaced by a less toxic schedule of methotrexate 3 g/m2 in a 3-hour infusion without IT therapy.
Erratum: Corrigendum: A common coding variant in CASP8 is associated with breast cancer risk
Authors: Angela Cox, Alison M Dunning, Montserrat Garcia-Closas, Sabapathy Balasubramanian, Malcolm W R Reed, Karen A Pooley, Serena Scollen, Caroline Baynes, Bruce A J Ponder, Stephen Chanock, Jolanta Lissowska, Louise Brinton, Beata Peplonska, Melissa C Southey, John L Hopper, Margaret R E McCredie, Graham G Giles, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Lorna Gibson, Stig E Bojesen, Børge G Nordestgaard, Christen K Axelsson, Diana Torres, Ute Hamann, Christina Justenhoven, Hiltrud Brauch, Jenny Chang-Claude, Silke Kropp, Angela Risch, Shan Wang-Gohrke, Peter Schürmann, Natalia Bogdanova, Thilo Dörk, Rainer Fagerholm, Kirsimari Aaltonen, Carl Blomqvist, Heli Nevanlinna, Sheila Seal, Anthony Renwick, Michael R Stratton, Nazneen Rahman, Suleeporn Sangrajrang, David Hughes, Fabrice Odefrey, Paul Brennan, Amanda B Spurdle, Georgia Chenevix-Trench, Jonathan Beesley, Arto Mannermaa, Jaana Hartikainen, Vesa Kataja, Veli-Matti Kosma, Fergus J Couch, Janet E Olson, Ellen L Goode, Annegien Broeks, Marjanka K Schmidt, Frans B L Hogervorst, Laura J Van't Veer, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, Sara Wedrén, Per Hall, Yen-Ling Low, Jianjun Liu, Roger L Milne, Gloria Ribas, Anna Gonzalez-Neira, Javier Benitez, Alice J Sigurdson, Denise L Stredrick, Bruce H Alexander, Jeffery P Struewing, Paul D P Pharoah, Douglas F Easton
Journal: Nature Genetics (2007)
A PROTEOLYTIC ENZYME PRODUCED BY GROUP A STREPTOCOCCI WITH SPECIAL REFERENCE TO ITS EFFECT ON THE TYPE-SPECIFIC M ANTIGEN
Authors: Stuart D. Elliott
Journal: The Journal of Experimental Medicine (1945)

1. Group A streptococci sometimes produce in broth culture an extracellular proteolytic enzyme. 2. Under suitable cultural conditions the enzyme has been demonstrated in representative cultures of most of the Griffith types. Its production by a given strain may be suppressed by serial passage through mice and the variant so produced has been found to maintain this change in character on subculture in artificial media. 3. Under certain conditions, the enzyme attacks the type-specific M antigens of all the group A streptococci so far tested, with the exception of that of type 28. The enzyme exhibits its maximal activity at 37 degrees C.: Extracts made from enzyme-producing cultures which have been grown at this temperature lack the M antigen; enzyme-producing strains may sometimes be induced to yield M substance in extracts by culturing the streptococci at 22 degrees C. Cultures which, when grown at 37 degrees C. yield M substance in extracts, do not produce the enzyme. 4. Human and rabbit fibrin are attacked and streptococcal fibrinolysin is also inactivated by the enzyme. Other susceptible substrates include casein, milk, gelatin, and benzoyl-l-arginineamide but not l-leucylglycylglycine. 5. The general properties of the enzyme resemble those of papain and some of the cathepsins: It is active under the reducing conditions produced in broth cultures by the presence of living bacteria; it is also activated by substances which reduce disulfide to sulfhydryl groups, e.g. potassium cyanide, cysteine, glutathione, and thioglycollic acid, but it is not activated by ascorbic acid. The enzyme is inactivated by iodoacetic acid and also by normal rabbit or mouse serum.
Bone Cancer Among Female Radium Dial Workers. Latency Periods and Incidence Rates by Time After Exposure: Brief Communication 2
Authors: Anthony P. Polednak
Journal: JNCI Journal of the National Cancer Institute (1978)

Bone cancer cases in 1,250 women exposed to radium while working in the luminous watch-dial industry between 1913 and 1929 were analyzed for times of appearance (“latency periods”) and incidence rates over time after first exposure. The lowest radium intake dose associated with bone cancer, among 751 women whose intake doses had been determined, was 202.5 μCi. Mean and median bone cancer latency periods tended to decline, but average survival among women without bone cancer also decreased with increasing intake level. Bone cancer incidence rates over time were compared in 2 intake-dose groups (200–749 and ≥750 μCi) by means of an actuarial method that takes competing risks into account. Incidence rates were consistently higher in the higher intake-dose group versus the lower dose group at each 5-year period after first exposure. The variability in the odds ratios across the time periods was not statistically significant, and the actuarial method provided little evidence for an effect of intake dose on the pattern of incidence rate over time. With the use of similar methods, no significant variability was evident in the relative odds of bone cancer over time after exposure between one group of women first exposed to radium at less than 18 years of age and another group exposed when 18 or more years old.
Cholesterol 7?-hydroxylase (CYP7A): Patterns of messenger RNA expression during rat liver development
Authors: Mara Massimi, Steven R. Lear, Sandra L. Huling, Albert L. Jones, Sandra K. Erickson
Journal: Hepatology (1998)

Cholesterol 7α-hydroxylase is a rate-limiting enzyme in bile acid synthesis, a major pathway for cholesterol catabolism. It plays a crucial role in postnatal development and survival. In an adult liver, its activity and messenger RNA (mRNA) are heterogeneously distributed with concentration in the pericentral area. We defined how the pattern of cholesterol 7α-hydroxylase mRNA evolves during rat liver development, correlated this with its total liver mRNA levels, and determined when its heterogeneous pattern of expression is established. Cholesterol 7α-hydroxylase mRNA was undetectable in 18-day-old fetal livers by Northern blot. It was increased markedly in newborns with a homogeneous liver lobular distribution as determined by in situ hybridization. At postnatal day four, mRNA levels were markedly decreased with concomitant appearance of a lobular gradient: mRNA was detected only in a few hepatocytes located around efferent venules. At 22 days, the time of highest mRNA expression, a marked extension of the gradient towards the periportal area was observed, indicating that the increase in total liver cholesterol 7α-hydroxylase mRNA level was a result of recruitment of hepatocytes upstream from the central vein area. By 28 days, the adult pattern was observed. Thus, expression of cholesterol 7α-hydroxylase mRNA is tightly regulated during rat liver development, both temporally and spatially supporting its critical role in normal postnatal development.
Cellular responses in experimental liver injury: Possible cellular origins of regenerative stem-like progenitor cells
Authors: William B. Coleman, D. Hunter Best, Hartmut Jaeschke, Kevin Mullen, Darius Moradpour
Journal: Hepatology (2005)

Background/Aims Mature hepatocytes divide to restore liver mass after injury. However, when hepatocyte division is impaired by retrorsine poisoning, regeneration proceeds from another cell type: the small hepatocyte-like progenitor cells (SHPCs). Our aim was to test whether SHPCs could originate from mature hepatocytes. Methods Mature hepatocytes were genetically labeled using retroviral vectors harboring the β-galactosidase gene. After labeling, retrorsine was administered to rats followed by partial hepatectomy to trigger regeneration. A liver biopsy was performed one month after surgery and rats were sacrificed one month later. Results We observed the proliferation of small hepatocytes arranged in clusters in liver biopsies. These cells expressed Ki67 antigen and displayed high mitotic index. At sacrifice, regeneration was completed and clusters had merged. A significant proportion of clusters also expressed β-galactosidase demonstrating their origin from labeled mature hepatocytes. Finally, the overall proportion of β-galactosidase positive cells was identical at the time of hepatectomy as well as in liver biopsy and at sacrifice. Conclusions The constant proportion of β-galactosidase positive cells during the regeneration process demonstrates that mature hepatocytes are randomly recruited to proliferate and compensate parenchyma loss in this model. Furthermore, mature hepatocytes are the source of SHPC after retrorsine injury.
Lung Clearance Index as an Outcome Measure for Clinical Trials in Young Children with Cystic Fibrosis. A Pilot Study Using Inhaled Hypertonic Saline
Authors: Padmaja Subbarao, Sanja Stanojevic, Meghan Brown, Renee Jensen, Margaret Rosenfeld, Stephanie Davis, Lyndia Brumback, Per Gustafsson, Felix Ratjen
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Lung clearance index (LCI), measured by multiple breath washout (MBW), is a noninvasive measure of ventilation inhomogeneity that holds promise as an objective physiologic endpoint for clinical trials in infants and preschool children with cystic fibrosis (CF).To study the feasibility of using LCI to assess treatment effect outcomes in CF trials of infants and preschoolers.The Infant Study of Inhaled Saline trial was a multicenter, randomized, controlled trial of hypertonic (7%) versus isotonic (0.9%) saline inhaled twice daily for 48 weeks in children with CF under 6 years of age. LCI measurements were performed in a single-center pilot substudy at baseline and 48 weeks using a respiratory mass spectrometer and sulfur hexafluoride as the tracer gas. LCI measurements were standardized using published normative data (zLCI) to account for height-related changes in LCI during early childhood. A generalized estimating equation model with an interaction between treatment group and test occasion was used to estimate a treatment effect.A total of 27 participants were randomized; 25 participants, aged (median [range]) 2.6 (0.34-4.95) years, had acceptable baseline and follow-up LCI measures. On average, LCI decreased in the hypertonic saline group (n = 12) by 1.19 z-scores units (95% confidence interval [CI] = -2.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = -0.40 to 2.02). A significant treatment effect was observed for zLCI (2.01; 95% CI = 0.26 to 3.76; P = 0.025).MBW testing is feasible in an interventional study in infants and preschool children with CF. These pilot findings support the development of MBW and LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.