tbuckley/cabot-search huggingface dataset:
Abstract 5621: MicroRNA 203 modulates glioma cell migration and invasion by targeting ROBO1
Authors: Sajani S. Lakka
Journal: Cancer Research (2012)

Abstract MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. A potential role for miRNAs in malignancy has been suggested by the location of the genes for several miRNAs at sites of translocation breakpoints or deletions linked to a specific neoplastic state. Allelic deletion on chromosome 14q plays an important role in the pathogenesis of GBM and was thought to harbor multiple tumor suppressor genes associated with GBM, a region which also encodes mir-203. Real-time PCR and insitu hybridization showed decreased levels of mir203 expression in anaplastic astrocytoma and glioblastoma tissues and cell lines. Exogenous expression of mir-203 using a plasmid expressing mir-203 precursor (pmir-203) suppressed cell invasion and migration in SNB19 glioblastoma cell line and 4910 xenograft cells. We determined that one relevant target of miR-203 was ROBO1, since miR-203 expression decreased mRNA and protein levels as determined by RT-PCR and western blot analysis. Moreover, cotransfection experiments using luciferase-based transcription reporter assay have shown direct regulation of ROBO1 3α-UTR regions by miR-203 which was significantly abrogated when mutating the predicted miR-203 seed regions in the pMIR-REPORT UTR constructs, thereby validating the direct interaction between miR-203 and the ROBO1 3α-UTRs. Concordantly, over expressing ROBO1 expression construct with no mir-203 binding site blocked pmir-203 mediated suppression of migration and invasion. Taken together these studies demonstrate that up regulation of Robo1 in response to the decrease in mir-203 in glioma cells is responsible for glioma tumor cell migration and invasion. 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 5621. doi:1538-7445.AM2012-5621
Relief of Reflux Symptoms after Endoscopic Gastroplication May Be Associated with Reduced Esophageal Acid Sensitivity: A Pilot Study
Authors: G. Wenzel, R. Kuhlbusch, J. Heise, T. Frieling
Journal: Endoscopy (2005)

Background and Study Aims: Although the new endoscopic techniques for the treatment of gastroesophageal reflux disease (GERD) lead to marked clinical benefit, the underlying mechanism of this is unknown. Materials and Methods: In this prospective study, the effect of endoscopic gastroplication was investigated in six patients with GERD, who were assessed before and 4 weeks after treatment. The effect on reflux symptoms, quality of life, proton pump inhibitor (PPI) consumption, reflux esophagitis, acid exposure, esophageal motility, lower esophageal sphincter pressure (LESP), and gastric emptying was measured. Esophageal acid sensitivity before and after treatment was investigated using a standardized acid provocation test, and compared with that of six age- and sex-matched healthy controls. Results: Significant clinical benefit and discontinuation of PPI consumption after gastroplication was seen. Among the objectively measured parameters, only acid exposure was significantly reduced and gastric emptying significantly delayed. However, acid exposure remained pathologically high. Esophageal acid sensitivity was significantly reduced. The induction of heartburn and/or pain was abolished in four patients after gastroplication. In two patients the intensity of heartburn/pain was significantly reduced by 40 % or 60 %, and the time to provoke heartburn/pain significantly prolonged by 40 % or 100 %. Conclusion: These preliminary data suggest that the decrease of esophageal sensitivity to acid after endoscopic gastroplication is part of the mechanism responsible for the reduction of reflux symptoms.
Role of ischemia in contrast-induced renal damage: an experimental study.
Authors: G Lund, S Einzig, J Rysavy, B Borgwardt, E Salomonowitz, A Cragg, K Amplatz
Journal: Circulation (1984)

Total and regional cortical blood flow was measured in dogs by the radioactive microsphere technique after renal damage of varying severity had been induced by combining selective injection of diatrizoate, iopamidol, or normal saline with a 10 min occlusion of the renal artery. There was extensive tubular and glomerular damage in the kidneys exposed to diatrizoate, but not in the kidneys exposed to saline. Iopamidol caused intermediate changes. Average cortical blood flow was reduced from baseline levels in all groups 5 min after perfusion was restored. After 1 hr the flow had returned to the baseline level. Analysis of variance did not show a statistically significant difference among the groups. A tendency for redistribution of flow from outer to inner cortical layers was seen, but this was present in all groups. The flow changes detected in this study cannot explain the varying severity of renal damage.
A Practice of Social Medicine: A South African Team's Experience in Different African Communities
Authors: Vincent J. Gagliardi
Journal: JAMA (1964)

The locale of this book is South Africa—among the Zulu-speaking tribes of rural Pholela and the inhabitants of the city of Durban (and its surrounding communities of varying ethnic and economic composition). Medical care, brought to these people by the Institute of Family and Community Living of the University of Natal, adapts itself to special community problems. If, for example, the men of a rural village migrate to the mines of Johannesburg, they leave their home area disproportionately populated with women and children. The result is poor farming, soil erosion, and malnutrition. The father makes a relatively good salary, but lives in squalid, crowded, migrant labor camps, and loses much of his money to liquor and entertainment. He may acquire a second wife there and return home less and less often. When he does he is likely to bring syphilis, previously unknown in rural villages. Such problems, both medical and
Recent molecular advances in the approach to early lung cancer detection and intervention.
Authors: J L Mulshine, F Scott, J Zhou, I Avis, M Vos, A M Treston
Journal: Environmental Health Perspectives (1997)

Lung cancer is a major contributor to overall cancer mortality. Detecting lung cancer while it is still a localized process is a long-cherished goal for improving the outcome of this disease. Recent developments suggest that we are approaching this capability. We next have to think about how to implement a change in our approach to lung cancer management to derive the benefit of better detection capability. This is an area in which our growing understanding of lung cancer biology is providing clues on improving the inhibition of cancer progression.
HIV infection: the challenge to general practitioners
Authors: P. Hodgkin
Journal: BMJ (1988)

The ability to control and treat the acquired immunodeficiency syndrome (AIDS) epidemic depends critically on care in the community, yet little is known about how primary care is responding to the challenge. The mere mention of AIDS raises huge anxieties for doctors as well as patients, and discussing sexual behavior rarely flows naturally from other aspects of routine consultations. Doctors should be discussing the risks of human immunodeficiency virus (HIV) infections with most adults attending for immunizations for overseas travel and many patients consulting about contraception. With regard to actual tests for HIV antibodies, positive results found by general practitioners, especially in cases where there is no major risk factor, should be treated as false positives until confirmed by specialized tests. Doctors should seek to use each consultation to educate the patient about HIV infection.
39 MK-5172: A NOVEL HCV NS3/4A PROTEASE INHIBITOR WITH POTENT ACTIVITY AGAINST KNOWN RESISTANCE MUTANTS
Authors: S. Carroll, J. McCauley, S. Ludmerer, S. Harper, V. Summa, M. Rowley, M. Rudd, P. Coleman, N. Liverton, J. Butcher, C. Mcintyre, J. Romano, K. Bush, M. Ferrara, B. Crescenzi, A. Petrocchi, M. Difilippo, C. Burlein, J. Dimuzio, D. Graham, C. Mchale, M. Stahlhut, A. Gates, C. Fandozzi, N. Trainor, D. Hazuda, J. Vacca, D. Olsen
Journal: Journal of Hepatology (2010)
Adventures in Nutrition: An Autobiography
Authors: Stanley M. Garn
Journal: JAMA (1991)

On December 7, 1941, Dr Frederick Stare arrived in Boston at the express invitation of Baird Hastings to consider a new Rockefeller-sponsored position in nutrition at the Harvard Medical School and the School of Public Health. With a PhD in nutrition from Wisconsin, an MD from the University of Chicago, and some 25 publications in the biochemical literature, he was a very well-qualified 30-year-old, and he was appointed as an assistant professor and chairman of the new department. What he then accomplished, with the collaboration of outstanding colleagues, is a surpassing record of achievements that continues to the present day. As we learn in this autobiography, Stare was able to build up a substantial endowment of nearly $30 million from private industry and philanthropic sources. Grants and contracts provided an equal amount of directed support. The Department of Nutrition at Harvard became known for research on lipid metabolism, obesity, diabetes,
Autoimmune pancreatitis--also a Western disease
Authors: R Sutton
Journal: Gut (2005)

Autoimmune pancreatitis is recognised worldwide as a T cell mediated, organ specific disease characterised by lymphocytic infiltration of the exocrine parenchyma with fibrosis and autoantibodies, including to carbonic anhydrase II. Increasing use of biopsy at endoscopic ultrasound may permit more frequent diagnosis without resection, but if doubt remains as to the presence of neoplasia, resection is preferable

During the five decades after Hashimoto described struma lymphomatosa of the thyroid gland featuring diffuse lymphocytic infiltration, fibrosis, and parenchymal atrophy,1 autoimmunity became increasingly recognised, such that when similar histological changes were described affecting the pancreas, an autoimmune mechanism was postulated.2 Autoimmune pancreatitis then remained among a number of plausible explanations for the appreciable minority of patients with chronic pancreatitis who give no history of alcohol abuse.3 More recently, Japanese workers again took up the baton, describing series of patients who had undergone pancreatic resection for suspected neoplasia but whose histology demonstrated lymphocytic infiltration of the exocrine parenchyma, with periductular and interlobular fibrosis.4,5 Further study demonstrated a T cell predominance to the infiltrate,5 autoantibodies directed against carbonic anhydrase II,6 an enzyme present in pancreatic as well as salivary ductal epithelium, and frequently high serum levels of IgG4.7 These findings have been confirmed in the European population, as reported by Aparisi et al in this issue of Gut ,8 who describe a small series within a larger group of patients with non-alcoholic chronic pancreatitis (see page 703) . Although not stated, such a group is highly likely to include patients with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR)9 and serine protease inhibitor Kazal type 1 (SPINK1)10 which both increase the risk of chronic pancreatitis, as well as mutations of cationic trypsinogen (protease, serine, 1 (trypsin 1): PRSS1) which cause hereditary …
Stem cell and epithelial-mesenchymal transition markers on circulating tumor cells in patients with metastatic breast cancer.
Authors: B Aktas, M Tewes, S Hauch, T Fehm, R Kimmig, S Kasimir-Bauer
Journal: Cancer Research (2009)

Abstract Abstract #107 Background: Stem cell like tumor cells have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, these cells may undergo phenotypic changes, known as epithelial-mesenchymal transition (EMT), which allows them to travel to the site of metastasis formation without getting affected by conventional treatment. Assuming that metastasis requires a dissemination of tumor stem cells or tumor cells showing EMT, it was the purpose of this study to identify these cells among circulating tumor cells (CTC) in blood samples of 28 metastatic breast cancer patients.&amp;#x2028; Materials and Methods: 5 ml blood was analyzed for EpCAM, MUC-1 and HER-2 transcripts with the AdnaTest BreastCancer (AdnaGen AG). The recovered c-DNA was additionally multiplex tested for three EMT markers [Twist, Akt2, PI3K (TAP)] and separately for the tumor stem-cell marker ALDH1. The analytical sensitivity was determined by the detection of a low number of target cells (5 IGROV cells spiked into 5 ml blood of healthy donors) using the AdnaTest BreastCancer procedure. The identification of EMT markers was considered positive if at least one marker was detected in the sample. Healthy donor samples without spiked tumor cells were used to determine the specificity of the test. The resulting PCR fragments were separated and quantified using the Agilent Bioanalyzer 2100.&amp;#x2028; Results: Applying an amplicon cut-off value of 0.2 ng/μl for Akt2, 0.15 ng/μl for Twist, 0.25 ng/μl for PI3K and 0.15 ng/μl for ALDH1, 97% of 30 healthy donor samples investigated were negative for TAP and 95% for ALDH1 transcripts. The spiking experiments revealed 80% recovery of the IGROV cells. CTC were detected in 12/28 (43%) breast cancer samples. All samples were further examined for tumor stem cell or TAP markers. In the CTC (+) group 50% were positive for at least one of the TAP markers and 42% for ALDH1. In the CTC (-) group the percentages were 19% and 12%, respectively. The expression of TAP and/or stem cell markers in CTC was compared with the clinical follow up results. In CTC (+) patients diagnosed as non-responders the expression of TAP and ALDH1 was found in 5/12 (40%) samples. In the CTC (+) responder group only one sample expressed TAP and no positive case was found for ALDH1. In the CTC (-) non-responder group 1/14 samples was positive for TAP and ALDH1. 2/14 (14%) of CTC (-) responders were positive for TAP and 1/14 for ALDH1, respectively.&amp;#x2028; Conclusion: A major proportion of CTC found in the blood of metastatic breast cancer patients shows EMT and tumor stem cell characteristics supporting the hypothesis that these markers are an indicator for therapy resistant tumor cell populations and, therefore, for an inferior prognosis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 107.
Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution
Authors: Jamie C. Stanford, Christian Young, Donna Hicks, Philip Owens, Andrew Williams, David B. Vaught, Meghan M. Morrison, Jiyeon Lim, Michelle Williams, Dana M. Brantley-Sieders, Justin M. Balko, Debra Tonetti, H. Shelton Earp, Rebecca S. Cook
Journal: Journal of Clinical Investigation (2014)

Breast cancers that occur in women 2-5 years postpartum are more frequently diagnosed at metastatic stages and correlate with poorer outcomes compared with breast cancers diagnosed in young, premenopausal women. The molecular mechanisms underlying the malignant severity associated with postpartum breast cancers (ppBCs) are unclear but relate to stromal wound-healing events during postpartum involution, a dynamic process characterized by widespread cell death in milk-producing mammary epithelial cells (MECs). Using both spontaneous and allografted mammary tumors in fully immune-competent mice, we discovered that postpartum involution increases mammary tumor metastasis. Cell death was widespread, not only occurring in MECs but also in tumor epithelium. Dying tumor cells were cleared through receptor tyrosine kinase MerTK-dependent efferocytosis, which robustly induced the transcription of genes encoding wound-healing cytokines, including IL-4, IL-10, IL-13, and TGF-β. Animals lacking MerTK and animals treated with a MerTK inhibitor exhibited impaired efferocytosis in postpartum tumors, a reduction of M2-like macrophages but no change in total macrophage levels, decreased TGF-β expression, and a reduction of postpartum tumor metastasis that was similar to the metastasis frequencies observed in nulliparous mice. Moreover, TGF-β blockade reduced postpartum tumor metastasis. These data suggest that widespread cell death during postpartum involution triggers efferocytosis-induced wound-healing cytokines in the tumor microenvironment that promote metastatic tumor progression.
The Role of Blood from HLA-Homozygous Donors in Fatal Transfusion-Associated Graft-versus-Host Disease after Open-Heart Surgery
Authors: Michael Thaler, Arie Shamiss, Shlomit Orgad, Monica Huszar, Naomi Nussinovitch, Simcha Meisel, Ephraim Gazit, Jacob Lavee, Aram Smolinsky
Journal: New England Journal of Medicine (1989)

Acute graft-versus-host disease has been described in immunocompromised patients receiving nonirradiated blood products.1 2 3 In addition to the involvement of the skin, liver, and gut typically seen in graft-versus-host disease after bone marrow transplantation,4 these patients have bone marrow involvement that results in pancytopenia. The aplasia observed in graft-versus-host disease is presumably due to recognition by the donor's immune-reactive cells of histoincompatible antigens on the host's hematopoietic precursor cells. Transfusion-associated graft-versus-host disease carries a high mortality rate; most patients succumb to infection.2 Because the onset of transfusion-associated graft-versus-host disease is delayed and because its symptoms are similar to those seen in . . .
Old and New Ways to Repair Inguinal Hernias
Authors: Jonathan L. Meakins, Jeffrey S. Barkun
Journal: New England Journal of Medicine (1997)

Inguinal hernias have been a problem since prehistory, and through recorded time, surgeons have attempted to repair them. A coherent anatomical basis for repair awaited Bassini's classic description in 1889: suture of the conjoined tendon (internal oblique and transverse muscles with the incised fascia transversalis) to Poupart's (inguinal) ligament.1 Modern conventional repairs are a variation on Bassini's original work. The two best-known techniques are the Cooper ligament repair (interrupted sutures approximating the conjoined tendon to Cooper's ligament with a relaxing incision on the external oblique aponeurosis)2 and the Shouldice technique (approximating with great precision the above anatomical elements in four . . .
THE SKIN ERUPTIONS OF CODEINE
Authors: MAX SCHEER
Journal: JAMA (1934)

Codeine has been in use for the past fifty years and is today one of the most widely employed narcotics. As far back as 1832 it was extracted from opium and in 1881 its chemical formula was determined to be the methyl ester of morphine.<sup>1</sup>Despite its extensive use, proved cases of codeine exanthems due to hypersensitivity are rare. It is not even mentioned by Morrow<sup>2</sup>in his classic monograph on drug eruptions or by Lewin,<sup>3</sup>although the cutaneous manifestations of morphine and opium were well known to these authors. In 1874, Bardet<sup>4</sup>studied the comparative effects of codeine, morphine and narceine. Using large doses of codeine (from 0.2 to 0.4 Gm.) he found that itching occurred almost constantly in himself as well as in several patients. In two instances he noted a more or less generalized associated erythema, once in himself and once in a
Diagnostic Performance of Low-Radiation-Dose Coronary Computed Tomography Angiography
Authors: Hatem Alkadhi, Moritz Wyler von Ballmoos
Journal: Annals of Internal Medicine (2011)

Letters16 August 2011Diagnostic Performance of Low-Radiation-Dose Coronary Computed Tomography AngiographyHatem Alkadhi, MD, MPH and Moritz Wyler von Ballmoos, MD, PhD, MPHHatem Alkadhi, MD, MPHFrom University Hospital Zurich, Zurich CH-8091, Switzerland.Search for more papers by this author and Moritz Wyler von Ballmoos, MD, PhD, MPHFrom University Hospital Zurich, Zurich CH-8091, Switzerland.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-4-201108160-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Drs. Salavati and Radmanesh for their interest in our study. They touch on several important points of statistical analysis in research synthesis of studies on diagnostic tests.Data obtained from diagnostic test studies with a binary outcome frequently tend to be overdispersed. This requires appropriate analytic methodology for calculation of unbiased estimates and valid test statistics. We fitted nonlinear mixed models to calculate parameter estimates by maximizing an approximation to the likelihood integrated over the random effects and used the second derivative matrix of the likelihood function to compute approximate standard errors as described elsewhere (1).... References1. Harbord RM, Deeks JJ, Egger M, Whiting P, Sterne JA. A unification of models for meta-analysis of diagnostic accuracy studies. Biostatistics. 2007;8:239-51. [PMID: 16698768] CrossrefMedlineGoogle Scholar2. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539-58. [PMID: 12111919] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University Hospital Zurich, Zurich CH-8091, Switzerland.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2039. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-analysis: Diagnostic Performance of Low-Radiation-Dose Coronary Computed Tomography Angiography Moritz Wyler von Ballmoos , Bernhard Haring , Pascal Juillerat , and Hatem Alkadhi Diagnostic Performance of Low-Radiation-Dose Coronary Computed Tomography Angiography Ali Salavati and Farid Radmanesh Metrics 16 August 2011Volume 155, Issue 4Page: 278-279KeywordsAngiographyComputed axial tomographyConflicts of interestDisclosureResearch and reporting methodsStatistical dataTest statisticsTouch ePublished: 16 August 2011 Issue Published: 16 August 2011 CopyrightCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Regulation of cyclin G1 during murine hepatic regeneration following dipin-induced DNA damage
Authors: Michael Rugaard Jensen, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Hepatology (1998)

Cyclin G1 has been linked to both positive and negative growth regulation. The expression of cyclin G1 is induced by transforming growth factor beta1 and p53, as well as by multiple mitogenic stimuli in mammalian cells in culture. However, the physiological role of cyclin G1 remains unclear. To examine the cell-cycle regulation of cyclin G1 in vivo, two models of coordinated cell proliferation induced by partial hepatectomy (PH) in the presence or absence of DNA damage were used. To introduce DNA damage, mice were treated with the alkylating drug, 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin) 2 hours before PH. Cell-cycle progression was monitored by 5-bromo-2-deoxyuridine (BrdU) incorporation into the DNA, the frequency of mitoses, the expression of cell-cycle control genes, and by flow cytometry. Dipin treatment resulted in cell-cycle arrest at the G2/M boundary without affecting G0/G1 and G1/S transitions. While the hepatocytes progressively entered G2 phase arrest, the cyclin G1 mRNA and protein levels increased more than five- and eightfold, respectively. Cyclin G1 had a nuclear localization in all interphase cells with clear absence from nucleoli. In contrast, during mitosis, cyclin G1 was undetectable by immunohistochemistry. Taken together, our data provide evidence for a putative role of cyclin G1 in G2/M checkpoint control.