tbuckley/cabot-search huggingface dataset:
Abstract 4339: Prostate adenocarcinoma and intensive bone remodeling in a new prostate cancer IGR-CaP1 preclinical model derived from a human primary tumor
Authors: Nader AL NAKOUZI, Paule OPOLON, Olivia BAWA, Stéphanie LERONDEL, Alain LEPAPE, Patrick GONIN, Christophe MASSARD, Karim FIZAZI, Anne CHAUCHEREAU
Journal: Cancer Research (2010)

Abstract Background: Bone metastasis is a frequent and catastrophic consequence of prostate cancer for which new therapeutics are needed. Although animal models of bone metastatic prostate cancer are necessary for understanding disease mechanism, there is currently no animal model that recapitulates spontaneous clinical bone metastases. We recently obtained the new prostate cell line IGR-CaP1 derived from primary epithelial prostate cancer. In vitro characterization indicates that IGR-CaP1 corresponds to basal epithelial cells expressing cancer stem cell markers and showing TP53 and PTEN mutations. Methods: We realized orthotopic xenografts in male nude mice and used bioluminescence imaging (BLI) that allows the sensitive detection of luciferase-expressing IGR-CaP1 cells to monitor tumor growth. Bone lesions were observed after direct intratibial injections of 5×105 luciferase-expressing IGR-CaP1 cells and were evaluated by both Computerized Tomography (CT) and micro Single-Photon Emission Computed Tomography (SPECT) measuring the bone fixation of 99Tc methylenediphosphonate (m99Tc-MDP). Results: Orthotopic injection of IGR-CaP1 cells yielded an undifferentiated prostate adenocarcinoma capable of metastasizing mainly to the liver and lung. Contrasting with the widely used PC3 preclinical model showing only osteolytic activity after bone injection, high resolution CT scan showed both lytic lesions in the cortical bone and osteoblastic lesions in the trabecular bone in 86% of the IGR-CaP1-injected mice (6/7). The mixed nature of the lesions and the intensive bone remodeling were confirmed by bone scintigraphy with a ∼5 fold increase in m99Tc-MDP fixation in injected tibia versus control tibia (P=0.0013). Conclusion: IGR-CaP1 is a rare model issued from a primary tumor able to reconstitute prostate adenocarcinoma in animals. Characterization of this new model of prostate cancer will provide investigators with an exceptional tool for developing approaches that prevent and treat prostate cancer bone metastases. In this way, micro SPECT/CT imaging provides a useful and quantitative tool for evaluating bone-targeting therapeutic strategies. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4339.
Targeting RAD51 phosphotyrosine-315 to prevent unfaithful recombination repair in BCR-ABL1 leukemia
Authors: Artur Slupianek, Yashodhara Dasgupta, Shu-yue Ren, Ewa Gurdek, Milene Donlin, Margaret Nieborowska-Skorska, Fabrice Fleury, Tomasz Skorski
Journal: Blood (2011)
Tuberous Sclerosis Complex Suppression in Cerebellar Development and Medulloblastoma: Separate Regulation of Mammalian Target of Rapamycin Activity and p27Kip1 Localization
Authors: Bobby Bhatia, Paul A. Northcott, Dolores Hambardzumyan, Baskaran Govindarajan, Daniel J. Brat, Jack L. Arbiser, Eric C. Holland, Michael D. Taylor, Anna Marie Kenney
Journal: Cancer Research (2009)

During development, proliferation of cerebellar granule neuron precursors (CGNP), candidate cells-of-origin for the pediatric brain tumor medulloblastoma, requires signaling by Sonic hedgehog (Shh) and insulin-like growth factor (IGF), the pathways of which are also implicated in medulloblastoma. One of the consequences of IGF signaling is inactivation of the mammalian target of rapamycin (mTOR)-suppressing tuberous sclerosis complex (TSC), comprised of TSC1 and TSC2, leading to increased mRNA translation. We show that mice, in which TSC function is impaired, display increased mTOR pathway activation, enhanced CGNP proliferation, glycogen synthase kinase-3 alpha/beta (GSK-3 alpha/beta) inactivation, and cytoplasmic localization of the cyclin-dependent kinase inhibitor p27(Kip1), which has been proposed to cause its inactivation or gain of oncogenic functions. We observed the same characteristics in wild-type primary cultures of CGNPs in which TSC1 and/or TSC2 were knocked down, and in mouse medulloblastomas induced by ectopic Shh pathway activation. Moreover, Shh-induced mouse medulloblastomas manifested Akt-mediated TSC2 inactivation, and the mutant TSC2 allele synergized with aberrant Shh signaling to increase medulloblastoma incidence in mice. Driving exogenous TSC2 expression in Shh-induced medulloblastoma cells corrected p27(Kip1) localization and reduced proliferation. GSK-3 alpha/beta inactivation in the tumors in vivo and in primary CGNP cultures was mTOR-dependent, whereas p27(Kip1) cytoplasmic localization was regulated upstream of mTOR by TSC2. These results indicate that a balance between Shh mitogenic signaling and TSC function regulating new protein synthesis and cyclin-dependent kinase inhibition is essential for the normal development and prevention of tumor formation or expansion.
Atlas of Pediatric Physical Diagnosis
Authors: Frank K. Thorp
Journal: JAMA (1997)

This is the third, expanded edition of this widely acclaimed atlas, previously published 5 years ago. It is intended as a guide to visual recognition in making a correct diagnosis. While there exist a number of excellent pediatric texts about the process of physical diagnosis (history taking, techniques of physical examination, algorithms for differential diagnoses), none offer the massive number, range, and excellence of the illustrations of this atlas. As stated in the preface, "This book was envisioned by teachers and developed to aid students, residents, nurses and practitioners who care for children in the diagnosis of pediatric disorders. Our goal is to broaden the visual experience of the student and clinician through rapid visual examination or review of simple laboratory tests." In this edition, there has been revision and updating of each chapter with the addition of new information, diagnostic techniques, and references. New contributors and suggestions from readers
Reducing the neglected burden of viral hepatitis in Africa: Strategies for a global approach
Authors: Maud Lemoine, Serge Eholié, Karine Lacombe
Journal: Journal of Hepatology (2014)

The burden of liver disease may dramatically increase in the near future in Africa, where screening and access to care and treatment are hampered by inadequate disease surveillance, lack of high-quality tools to assess chronic liver disease, and underestimated needs for human and financial resources. Chronic hepatitis may be considered as silent and neglected killer, fuelled by many years of global inertia from stakeholders and policy makers alike. However, the global battle against viral hepatitis is facing a new era owing to the advent of highly effective drugs, innovative tools for screening and clinical follow-up, and recent signs that governments, advocacy groups and global health organizations are mobilizing to advocate universal access-to-treatment. This review details the barriers to prevention, screening and treatment of viral hepatitis on the African continent, focuses on the urgent need for operational and research programmes, and suggests integrated ways to tackle the global epidemic.
One in 12 children dies before age 5 from preventable disease
Authors: F. Fleck
Journal: BMJ (2002)

A 12 year study on the world's children to be presented at a United Nations conference in May concluded that child mortality is still high despite a decade of unprecedented economic growth.

The study found that while child mortality fell by 11%, from 93 to 83 deaths per 1000 live births during the 1990s—1 in every 12 children dies before age 5 from preventable diseases.

The 102 page study—an update of a 1990 report covering child heath, education, nutrition, and protection in nearly 150 countries—concluded that healthy and educated children are vital …
Accuracy of Screening for Inhalational Anthrax after a Bioterrorist Attack
Authors: Nathaniel Hupert, Gonzalo M.L. Bearman, Alvin I. Mushlin, Mark A. Callahan
Journal: Annals of Internal Medicine (2003)

Background: Bioterrorism using anthrax claimed five lives in the United States in 2001 and remains a potential public health threat. In the aftermath of a large-scale anthrax attack, mass screening to identify early inhalational anthrax may improve both the management of individual cases and the efficiency of health resource utilization. Purpose: To develop the evidence base for outpatient anthrax screening protocols by quantifying differences in clinical presentation between inhalational anthrax and common viral respiratory tract infections. Design: Review, compilation, and data extraction from English-language case reports of inhalational anthrax and epidemiologic studies of influenza and other viral respiratory infections. Data Sources: 13 reports of 28 cases of inhalational anthrax from 1920 to 2001 and 5 studies reporting on the clinical features of 2762 cases of influenza and 1932 cases of noninfluenza viral respiratory disease. Data Synthesis: Characterization of presenting clinical symptoms in anthrax and viral disease and calculation of likelihood ratios for the presence of selected clinical features. Results: Fever and cough do not reliably discriminate between inhalational anthrax and viral respiratory tract infection. Features suggestive of anthrax include the presence of nonheadache neurologic symptoms (positive likelihood ratio cannot be calculated), dyspnea (positive likelihood ratio, 5.3 [95% CI, 3.7 to 7.4]), nausea or vomiting (positive likelihood ratio, 5.1 [CI, 3.0 to 8.5]), and finding of any abnormality on lung auscultation (positive likelihood ratio, 8.1 [CI, 5.3 to 12.5]). In contrast, rhinorrhea (positive likelihood ratio, 0.2 [CI, 0.1 to 0.4]) and sore throat (positive likelihood ratio, 0.2 [CI, 0.1 to 0.5]) are more suggestive of viral respiratory tract infection. Conclusion: Inhalational anthrax has characteristic clinical features that are distinct from those seen in common viral respiratory tract infections. Screening protocols based on these features may improve rapid identification of patients with presumptive inhalational anthrax in the setting of a large-scale anthrax attack.
Evaluation of a New Heparin Agent in Percutaneous Coronary Intervention
Authors: Sunil V. Rao, Chiara Melloni, Shelley Myles-DiMauro, Samuel Broderick, Andrzej S. Kosinski, Neal S. Kleiman, Vladimír Dzavík, Jean Francois Tanguay, Harish Chandna, Roger Gammon, Ernesto Rivera, John H. Alexander, Ian Fier, James Roach, Richard C. Becker
Journal: Circulation (2010)

Background— Factor Xa and factor IIa (thrombin) play roles in thrombotic complications after percutaneous coronary intervention. M118 is a novel low–molecular-weight heparin that has been rationally designed to capture the desired attributes of unfractionated heparin (UFH) and low–molecular-weight heparin: Potent activity against factor Xa and IIa, predictable pharmacokinetics after both intravenous and subcutaneous administration, ability to be monitored by use of point-of-care coagulation assays, and reversibility with protamine sulfate. We performed a phase 2 randomized trial to evaluate the safety and feasibility of M118 in the setting of elective percutaneous coronary intervention. Methods and Results— Overall, 503 patients undergoing elective percutaneous coronary intervention at 43 centers in the United States and Canada were randomized in an open-label fashion to 1 of 4 arms: UFH 70 U/kg, M118 50 IU/kg IV, M118 75 IU/kg IV, or M118 100 IU/kg IV. The primary outcome was the composite of death, myocardial infarction, repeat revascularization, stroke, thrombocytopenia, catheter thrombus, bailout use of glycoprotein IIb/IIIa inhibitor, or any bleeding through 30 days. The primary end point occurred in 31.1% of patients randomized to UFH and in 22.7%, 28.3%, and 30.1% of patients randomized to M118 50, 75, and 100 IU/kg, respectively. The primary analysis comparing the rates of the primary end points between the pooled M118 groups versus UFH demonstrated that M118 was noninferior to UFH at preventing percutaneous coronary intervention–related complications (28.4% pooled M118 arms versus 31.1% UFH). The adverse event profiles of M118 and UFH were comparable. Conclusions— This phase 2 randomized trial demonstrates that M118 is well tolerated and feasible to use as an anticoagulant in patients undergoing elective percutaneous coronary intervention and forms the basis for further investigation of this agent in ischemic heart disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543400.
THE OPERATIVE TREATMENT OF CRANIAL DEPRESSION: (GREENSTICK FRACTURE OF THE SKULL)
Authors: Jas. H. Nicoll
Journal: BMJ (1903)

Knu is required.The observance of three cardinal rules of diagnosis prevents any serious blunder.First: Look ;it the whole patient.Secondly: Examine the whole of the diseased part, limb, or structure, and at rest.Thirdly: Compare the two sides of the body.Again, by looking at the whole patient, how much can be taken in at a glance " in a moment of time, for thought is quick."After awhile you may learn to guess the patients social position, character, mental peculiarities, general health, and perhaps the disease.Habits of rapid observation and of
Plasma Volume Prior to and Following Volume Loading During Shock Complicating Acute Myocardial Infarction
Authors: PROTASIO L. DA LUZ, MAX HARRY WEIL, VINNIE Y. LIU, HERBERT SHUBIN
Journal: Circulation (1974)

Blood volume was measured following onset of shock in 19 patients who had sustained acute myocardial infarction. The plasma volume was measured by dilution technique utilizing R 125 ISA and the red cell mass by ( 51 Cr) red cell tag, at the time of admission. The plasma volume in six survivors was 41.1 ± 3.3 ml/kg; in 13 fatal cases it was 44.7 ± 4.0 ml/kg; this difference was not significant. The red cell mass in four survivors was 27.2 ± 1.75 ml/kg and in four fatal cases, 24.7 ± 1.60 ml/kg. Since these measurements are within normal ranges, we excluded absolute hypovolemia as a significant factor in accounting for the circulatory failure. Infusion of fluids in amounts which maintained a positive fluid balance selectively increased the plasma volume (57.1 ± 4.4 ml/kg), cardiac index, stroke volume and central blood volume in survivors, and reversed arterial vasoconstriction and lactic acidosis. However, the plasma volume was unaffected in the fatal cases (44.4 ± 4.0 ml/kg) and this was associated with progressive hemodynamic and metabolic deterioration. These observations support the hypothesis that recovery from shock is associated with expansion of plasma volume. To the contrary, during fatal progression of shock, plasma volume expansion does not occur despite volume loading.
Photodynamic Diagnosis (5-Aminolevulinic Acid) of Transitional Cell Carcinoma After Bacillus Calmette-Guérin Immunotherapy and Mitomycin C Intravesical Therapy
Authors: Ronald O.P. Draga, Matthijs C.M. Grimbergen, Esther T. Kok, Trudy N. Jonges, Christiaan F.P. van Swol, J.L.H. Ruud Bosch
Journal: European Urology (2009)
Clinical Protocols in Obstetrics and Gynecology
Authors: Ronald T. Burkman
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
868 TREATMENT WITH TELAPREVIR-BASED THERAPY AFTER EXPOSURE TO PEG-IFN/RBV IN THE REALIZE STUDY: RESULTS FROM THE PHASE IIIB C219 ROLLOVER STUDY
Authors: P. Mathurin, C. Sarrazin, H.W. Reesink, O. Weiland, M. Diago, G. Dusheiko, A. Ascione, Z. Ben-Ari, L.G. Lyra, W. Sievert, M. Gschwantler, T.I. Hassanien, E. Janczewska, K. Janssen, D. Luo, A. Ghys, S. De Meyer, G. Picchio, K. de Backer, J. Witek
Journal: Journal of Hepatology (2013)
Opportunist pulmonary infection with Legionella bozemanii.
Authors: C R Swinburn, F K Gould, P A Corris, T L Hooper, N J Odom, R Freeman, C G McGregor
Journal: Thorax (1989)

Three cases of pulmonary Legionella bozemanii infection in immunocompromised patients are described. The diagnosis was made by culture in each case and would not otherwise have been made, and it is recommended that a culture specific for Legionella species should be included in the investigation of patients with suspected opportunist pulmonary infections.
Lymphocyte‐specific murine deubiquitinating enzymes induced by cytokines
Authors: Kwang‐Hyun Baek
Journal: American Journal of Hematology (2002)

Abstract It is becoming clear that a number of proteins regulating cellular mechanisms for homeostasis in all eukaryotes are controlled not only by phosphorylation and dephosphorylation but also by ubiquitination and deubiquitination. This includes most of oncoproteins and signaling components involved in receptor tyrosine kinase (RTK)‐mediated signal transduction pathways. Like protein phosphorylation and dephosphorylation regulated by kinases and phosphatases, respectively, protein ubiquitination and deubiquitination are very dynamic and are regulated by ubiquitin conjugating enzymes and deubiquitinating (DUB) enzymes. A number of deubiquitinating enzymes have been isolated even though little is known about their biological functions. This review concentrates on recent findings and new insights into DUB enzyme subfamily members in lymphocytes. Am. J. Hematol. 71:340–345, 2002. © 2002 Wiley‐Liss, Inc.
Chemotherapy Parity Laws
Authors: Bo Wang, Steven Joffe, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Phosphatidylinositol 3-Kinase/Akt Signaling Controls Endothelial Cell Sensitivity to Fas-Mediated Apoptosis via Regulation of FLICE-Inhibitory Protein (FLIP)
Authors: Toshimitsu Suhara, Toshiaki Mano, Beatriz Enes Oliveira, Kenneth Walsh
Journal: Circulation Research (2001)

Abstract —Fas is constitutively expressed on endothelial cells, but in contrast to smooth muscle and other cell types, endothelial cells are highly resistant to Fas-mediated apoptosis. In this study, we examined the role of the serine/threonine kinase Akt/PKB in controlling the sensitivity of endothelial cells to Fas-mediated apoptosis. Serum deprivation inhibited expression of the caspase-8 inhibitor FLICE-inhibitory protein (FLIP), which functions downstream from Fas. FLIP expression levels were restored when serum-depleted cells were treated with vascular endothelial growth factor. Treatment with the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors wortmannin or LY294002 or infection of the adenoviral construct expressing dominant-negative Akt (Adeno-dnAkt) also inhibited the expression of FLIP in endothelial cells, whereas the MEK inhibitor PD98059 had no effect. Conversely, adenovirus-mediated transfection of a constitutively-active Akt gene abolished the wortmannin- and LY294002-mediated downregulation of FLIP. Suppression of PI 3-kinase signaling sensitized endothelial cells to Fas-mediated apoptosis. Under conditions of suppressed PI 3-kinase signaling, restoration of FLIP expression reversed the induced sensitivity of endothelial cells to Fas-mediated apoptosis. These data suggest that inhibition of Fas-mediated apoptosis, via promotion of FLIP expression, is a mechanism through which Akt signaling can promote endothelial cell survival.
OC-032 Surveillance Leads To Improved Outcomes For Patients With Hepatocellular Carcinoma (hcc)
Authors: TJS Cross, W Ding, PD Richardson, F Yousef, D Palmer, E Joekes, C Farrell, J Evans
Journal: Gut (2014)

<h3>Introduction</h3> 6-monthly ultrasound surveillance is recommended in cirrhotic patients at risk of HCC. The benefit of surveillance has never been demonstrated in a western population. <h3>Methods</h3> A retrospective, single centre cohort analysis in patients diagnosed with HCC from 2008–2013. From 2008 an automated recall system for 6-monthly ultrasound was instigated by the radiology department, in preference <i>ad hoc </i>ultrasound requests. Patients with abnormal lesions proceeded to CT, MRI or liver biopsy according to defined international criteria. The primary end-points evaluated were stage of cancer detection (early i.e. BCLC 0 or A), versus late presentation (BCLC B-D) and patient survival from time of diagnosis to 12 months and 60 months. <h3>Results</h3> 160 patients were identified. Surveillance status was known in 132 patients. Median patient age was 68 years (57–75), median number of lesions was one, diameter of largest lesion 30 mm (19–50), and AFP 19.5 (5–250). Patients under surveillance were more likely to have disease at a curative stage 67 vs. 39% (p = 0.006, OR 0.59 (0.41–0.84), and had better survival at 1 year 80 vs. 62% (p = 0.04, OR 0.77 (0.62–0.97), and at 5 years 60 vs. 41% (p = 0.046, OR 0.69 (0.48–0.98). On univariate analysis the following variables on survival were evaluated: Age (p = 0.11), Number HCC nodules (p = 0.31), Total diameter of lesions (p = 0.001), Diameter of largest lesion (p &lt; 0.001), AFP (p &lt; 0.001). The presence on imaging of extra-hepatic metastases (p = 0.006), lymph nodes (p = 0.004), and portal vein thrombosis p &lt; 0.001), were associated with poorer survival. <h3>Conclusion</h3> Surveillance for hepatocellular carcinoma leads to earlier diagnosis and improved survival. <h3>Disclosure of Interest</h3> None Declared.