tbuckley/cabot-search huggingface dataset:
Abstract A17: Non-RGD-based strategies to target the thyroid hormone receptor-integrin αvβ3: Lessons from myeloma cells.
Authors: Keren Cohen, Martin Ellis, Paul J. Davis, Aleck Hercbergs, Osnat Ashur-Fabian
Journal: Clinical Cancer Research (2015)

Abstract Introduction. Integrin αvβ3 is a plasma membrane structural protein expressed/activated in tumor cells and dividing blood vessel cells. The extracellular domain of αvβ3 has an Arg-Gly-Asp (RGD) recognition site that enables the integrin to bind specific extracellular matrix (ECM) proteins that contain the RGD sequence and to transduce the binding into discrete intracellular signals. Such ECM proteins have pivotal roles in solid tumors and the RGD site has been tested as a chemotherapeutic target. Recently, a receptor for thyroid hormone (L-thyroxine, T4; 3, 5, 3'-triiodo-L-thyronine, T3) has been described on αvβ3 that is distinct from the RGD recognition site and has been shown to mediate proliferative effects of T4 and T3 on solid tumor cells via the MAPK pathway. We have recently shown that similar T4- and T3-induced proliferation occurs in multiple myeloma (MM) cells. Actions of T4 and T3 at the non-RGD site can be blocked by tetraiodothyroacetic acid (tetrac), a naturally-occurring deaminated T4 analog. In addition, tetrac has anti-tumor effects that are independent of blockade of actions of T4 and T3. In this report, we define mechanisms of tetrac action in MM cells. Methods. MM cell lines (CAG, RPMI 8226, ARK, ARP-1, U266) and primary cultures of marrow cells from MM patients were grown with T4/T3 and with/without tetrac (100 nM-50 μM). Harvested cells were subjected to the following analyses: cell counts (FACS, CyQuant), viability (WST-1), cell cycle (FACS, PI), cell death (Annexin-PI ± pan-caspase inhibitor, ZVAD, FACS; cleaved caspase-3, cleaved PARP, western blots), DNA damage response (pATM and PARP, western blots) and transcription of apoptosis-relevant genes (RT-PCR). Results. Early (4-8 h) and late (24 h) effects of tetrac were observed. In the early phase, tetrac reduced cell proliferation (p &amp;lt;&amp;lt;0.05) and induced a DNA damage response (ATM and PARP) and apoptosis (cleaved caspase-3 and cleaved PARP). After 24 h, tetrac significantly (p &amp;lt; 0.05) reduced cell number and viability and induced apoptotic cell death, with a parallel increase in pro-apoptotic gene expression. Conclusion. The thyroid hormone-binding (non-RGD) site on integrin αvβ3 in myeloma cells appears to be a novel target for chemotherapy with tetrac. Citation Format: Keren Cohen, Martin Ellis, Paul J. Davis, Aleck Hercbergs, Osnat Ashur-Fabian. Non-RGD-based strategies to target the thyroid hormone receptor-integrin αvβ3: Lessons from myeloma cells. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A17.
Peter Alan Trott
Authors: Alan McKinna, Rosemary Millis
Journal: BMJ (2016)

Peter Alan Trott was not one to be deterred by adversity. Despite severe polio during national service he achieved a successful career in pathology. Having been educated at Repton School he read medicine at St John’s College, Cambridge. After his house jobs he was posted as resident medical officer to 2/7 Gurkha Rifles in Singapore, where he contracted a virulent polio infection. He was repatriated in an iron lung, straight to Stoke Mandeville and the inspiring Ludwig Guttmann. There he met a South African nurse, …
Abstract 13631: Therapeutic Inhibition of Mitochondrial Reactive Oxygen Species With Mito-tempo Reduces Diabetic Cardiomyopathy
Authors: Rui Ni, Tianqing Peng
Journal: Circulation (2015)

Introduction: The mitochondria are important sources of reactive oxygen species (ROS) in the heart. Mitochondrial ROS production and subsequent oxidative damage have been implicated in the pathogenesis of diabetic cardiomyopathy. We hypothesized that therapeutic strategies specifically targeting mitochondrial ROS may have benefit in diabetic cardiomyopathy. Hypothesis: We hypothesized that therapeutic inhibition of mitochondrial ROS with mito-TEMPO reduces diabetic cardiomyopathy. Methods: The mitochondria-targeted antioxidant mito-TEMPO was administrated after diabetes onset in a mouse model of streptozotocin (STZ)-induced type-1 diabetes and type-2 diabetic db/db mice. Cardiac adverse changes were analyzed and myocardial function assessed. Cultured adult cardiomyocytes were stimulated with high glucose, and single mitochondrial superoxide generation and cell death were measured. Results: Incubation with high glucose increased mitochondria superoxide generation in cultured adult cardiomyocytes, which was prevented by mito-TEMPO. Co-incubation with mito-TEMPO also abrogated high glucose-induced cell death. Mitochondrial ROS generation, and intracellular ROS formation and oxidative damage were induced in both type-1 and type-2 diabetic mouse hearts. Daily injection of mito-TEMPO for 30 days inhibited mitochondrial ROS generation, prevented intracellular ROS formation and oxidative damage, decreased apoptosis and reduced myocardial hypertrophy in diabetic hearts without change of blood glucose, leading to improvement of myocardial function in both type-1 and type-2 diabetic mice. Mechanistic study revealed that the protective effects of mito-TMEPO were associated with down-regulation of ERK1/2 phosphorylation in diabetic hearts and high glucose-stimulated cardiomyocytes. Conclusions: Therapeutic inhibition of mitochondrial ROS by mitochondria-targeted antioxidant mito-TEMPO reduced adverse cardiac changes and mitigated myocardial dysfunction in both type-1 and type-2 diabetic mice. Thus, mitochondria-targeted antioxidants may be an effective therapy for diabetic cardiac complications.
Antibiotic prophylaxis to prevent catheter-related infections in recombinant interleukin-2-treated patients.
Authors: C Orcese, A Borri, C Besana
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.10.1767 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2213110 Antibiotic prophylaxis to prevent catheter-related infections in recombinant interleukin-2-treated patients. C OrcesexC OrceseSearch for articles by this author , A BorrixA BorriSearch for articles by this author , C BesanaxC BesanaSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.10.1767 PDF "Antibiotic prophylaxis to prevent catheter-related infections in recombinant interleukin-2-treated patients.." Journal of Clinical Oncology, 8(10), pp. 1767–1768© 1990 by American Society of Clinical Oncology
The concept of culture in psychiatric residency education
Authors: E F Foulks
Journal: American Journal of Psychiatry (1980)

Diagnosis and treatment in psychiatry are heavily influenced by cultural factors. The author argues that the subject of culture warrants a place in the curriculum of psychiatric residency education. He outlines approaches to the teaching of cultural psychiatry that have been used successfully in several departments of psychiatry. He feels that although the medical model of understanding mental illness has demonstrated its effectiveness in chemotherapeutic, psychotherapeutic, and other treatments, the cultural model can often provide unique insights and approaches in patient care.
Case 4-1967
Authors: Felix C. Fleischner, Benjamin Castleman
Journal: New England Journal of Medicine (1967)

Presentation of Case First admission. A sixty-three-year-old man entered the hospital because of a head injury and for investigation of progressive dyspnea.Three weeks previously, when he came home from his office, a lump and some blood on the back of his head were observed. He was unable to relate what had happened and subsequently appeared normal except for a slight decrease in hearing. There was no history of tinnitus, dizzy spells, headache, loss of consciousness, seizures, weakness, paresthesias or difficul within locomoton or speech.For several years he had been dyspneic, with a chronic cough productive of up . . .
NeoSCOPE: A phase II randomized comparison of neoadjuvant oxaliplatin/capecitabine versus carboplatin/paclitaxel-based chemoradiation in operable esophageal cancer.
Authors: Thomas Crosby, Somnath Mukherjee, Chris Hurt, Sarah Gwynne, Simon Gollins, Andrew Rea Bateman, Wyn Griffith Lewis, Ganesh Radhakrishna, Maria Hawkins, Heike I. Grabsch, Ruby Ray, Ricky A. Sharma, Wendy Wade, Rhydian Maggs, Bethan Tranter, Ashley Roberts, Sue Hadlow, David Sebag-Montefiore, Tim Maughan, Gareth Griffiths
Journal: Journal of Clinical Oncology (2014)

TPS4144 Background: Both oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal cancer, but no randomized study has compared their efficacy/toxicity. This study compares the two regimens to identify the optimum regimen to take forward to a phase III trial against neo-adjuvant chemotherapy, the current standard in the UK. Methods: Eligibility: Resectable adenocarcinoma of oesophagus and Type 1-2 Gastro-Osophageal Junction; ≥T3 and/or ≥N1 staged with EUS and PET-CT; PS 0-1. Intervention: Both arms receive 2 cycles induction OXCAP (oxaliplatin 130mg/m2 D1, Cape 625mg/m2 D1-21, q 3wk) followed by randomization to OXCAP-RT (oxali 85mg/m2 Day 1,15,29; cape 625mg/m2 on days of RT; RT-45Gy/25 fractions/5weeks) or CarPac-RT (Carbo AUC2 and paclitaxel 50mg/m2 Day 1,8,15,22,29; RT-45Gy/25 fractions/5weeks). Restaging CT/PET-CT 4-6 weeks after CRT, and 2-phase oesophagectomy with 2-field lymphadenectomy 6-8 weeks after CRT. Primary End-Point: Pathological complete response. Secondary: 1) Feasibility of recruitment; Toxicity; 30-day surgical morbidity/mortality; resection margin positivity rate; median, 3- and 5-yr OS. Statistics: Randomised phase II with 1:1 randomisation; planned accrual 76 patients (38/arm) over 18 months. In each arm, this sample size gives 90% power and one-sided type 1 error of 10% to detect that pCR is not <15% but could be >35%. Interim safety analysis: Toxicity analysis after 10 patients have completed treatment. RT Quality Assurance: Pre-trial: Detailed RT protocol and guidance document, RT workshop, central evaluation of test-case contours and adequacy of RT plan. On-trial: Real-time central review of contours and plans of first 20 patients on trial, 1st case from each centre, and 10% of cases selected at random. Current Status: Activation: September 2013; Centres open: 10, in set-up:10; Recruitment: 13. Funding: Cancer Research UK. Sponsor: Velindre NHS Trust. Trials Unit: Wales Cancer Trials Unit. Eudract No: 2012-000640-10. Clinical trial information: NCT01843829.
Abstract P3-01-07: ESTIMATED RISK OF RADIATION-INDUCED BREAST CANCER FROM MAMMOGRAPHIC SCREENING
Authors: R Freitas-Junior, RS Correa, J-E Peixoto, RS Ferreira, RMN Tanaka
Journal: Cancer Research (2012)

Abstract Objective: Estimate the benefit–risk balance of mammography, as number of lives saved/lost in an opportunistic screening in the state of Goiás, Brazil, in 2010, according to type of technology available and age group indicated for screening. Methods: The number of lives saved was estimated considering the gross mortality rate for breast cancer, female population living in the state, estimated mortality rate reduction due to screening programs, and mammographic coverage in the state. For number of lives lost, the model adopted by the Biological Effects of Ionizing Radiation (BEIR VII) was used. Based on the mean glandular tissue dose (Dg), the following parameters were calculated: number of radiation-induced cancer cases with one exposure, with several exposures in screening programs and over the lifetime, number of deaths caused by radiation-induced cancer at a certain age and over the lifetime. Dg of each equipment was estimated according to the European protocol, using the incident air kerma (Ki) at the simulator entrance and the half-value layer (HVL) of the X-ray beam, and table values of coefficients to convert Ki into Dg. Ki and HVL were measured in 100 equipments in operation in the state. A standard breast simulator (5.3 cm thickness and 50% glandular tissue) was used. We considered a biannual mammographic screening with an exam routine composed of a cranio-caudal and a mediolateral oblique view and 40–70 and 50–70-year age groups. Results: The mean Dg was 4.28 (±1.06) and 6.61 (±3.67) for conventional and digital equipments, respectively (p &amp;lt; 0.001). A woman undergoing mammography at the age of 40 in a conventional equipment has a 0.243/100000 probability of radiation-induced cancer at the age of 60, whereas using a digital equipment, the probability is 0.375/100000. The number of cases of radiation-induced breast cancer over the lifetime and consequent deaths followed the differences in the doses employed according to type of technology (p &amp;lt; 0.001). The balance between lives saved and lost was 75.5 (1253.8/16.6) and 166.5 (849.4/5.1) for women screened at 40–70 and 50–70 years, respectively. Conclusions: Screening among 50–70-year-olds, performed biannually using conventional equipments, presented more benefits regarding radiation protection. The number of cases of radiation-induced breast cancer and consequent deaths reproduces the same ratio observed for the difference in the doses between the types of technology. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-07.
Clonal Chromosomal Anomalies Similar to CLL and Other Hematologic Malignancies Can Be Found in “Normal” Individuals
Authors: Cathy C Laurie, Cecelia A Laurie, Brooke Fridley, Erin Carlson, Stephanie A. Smoley, Ian W. Flinn, Martin S. Tallman, Elisabeth Paietta, Richard Weinshilboum, Neil E. Kay, Tait D. Shanafelt
Journal: Blood (2012)
Determinants of Patient-Oncologist Prognostic Discordance in Advanced Cancer
Authors: Robert Gramling, Kevin Fiscella, Guibo Xing, Michael Hoerger, Paul Duberstein, Sandy Plumb, Supriya Mohile, Joshua J. Fenton, Daniel J. Tancredi, Richard L. Kravitz, Ronald M. Epstein
Journal: JAMA Oncology (2016)

Patients with advanced cancer often report expectations for survival that differ from their oncologists' expectations. Whether patients know that their survival expectations differ from those of their oncologists remains unknown. This distinction is important because knowingly expressing differences of opinion is important for shared decision making, whereas patients not knowing that their understanding differs from that of their treating physician is a potential marker of inadequate communication.To describe the prevalence, distribution, and proportion of prognostic discordance that is due to patients' knowingly vs unknowingly expressing an opinion that differs from that of their oncologist.Cross-sectional study conducted at academic and community oncology practices in Rochester, New York, and Sacramento, California. The sample comprises 236 patients with advanced cancer and their 38 oncologists who participated in a randomized trial of an intervention to improve clinical communication. Participants were enrolled from August 2012 to June 2014 and followed up until October 2015.We ascertained discordance by comparing patient and oncologist ratings of 2-year survival probability. For discordant pairs, we determined whether patients knew that their opinions differed from those of their oncologists by asking the patients to report how they believed their oncologists rated their 2-year survival.Among the 236 patients (mean [SD] age, 64.5 [11.4] years; 54% female), 161 patient-oncologist survival prognosis ratings (68%; 95% CI, 62%-75%) were discordant. Discordance was substantially more common among nonwhite patients compared with white patients (95% [95% CI, 86%-100%] vs 65% [95% CI, 58%-73%], respectively; P = .03). Among 161 discordant patients, 144 (89%) did not know that their opinions differed from that of their oncologists and nearly all of them (155 of 161 [96%]) were more optimistic than their oncologists.In this study, patient-oncologist discordance about survival prognosis was common and patients rarely knew that their opinions differed from those of their oncologists.
Transcathether Valve Replacement and Valve Repair
Authors: Rebecca T. Hahn
Journal: Circulation Research (2016)

Transcatheter aortic valve replacement for treatment of aortic stenosis has now become an accepted alternative to surgical valve replacement for some patients. In addition, transcatheter mitral valve repair is also routinely used in high surgical risk patients with mitral regurgitation. Other transcatheter procedures are in rapid development. The current review attempts to summarize the procedures and echocardiographic imaging used for transcatheter valve replacement or valve repair.
Measurement of combat exposure, posttraumatic stress disorder, and life stress among Vietnam combat veterans
Authors: M J Friedman, C K Schneiderman, A N West, J A Corson
Journal: American Journal of Psychiatry (1986)

Two scales developed to assess combat exposure and posttraumatic stress disorder symptomatology in Vietnam veterans displayed very high reliability. High levels of posttraumatic stress disorder were associated with more current life stresses and other standardized indices of dysphoria.
Abstract 252: Generation of a Mouse ESC Reporter Line to Identify Purkinje-like Conduction System Cells
Authors: Karen Maass, Jia Lu, Fiona See, Guoxin Kang, Camila Delgado, Glenn I Fishman
Journal: Circulation Research (2014)

We have previously demonstrated that contactin2 (Cntn2) protein is enriched in Purkinje cells of the adult cardiac conduction system (CCS). Here we present a mouse embryonic stem cell (mESC) reporter line to identify Purkinje-like cardiomyocytes in vitro. Methods and Results: Dual reporter Purkinje cell mESC were generated from Cntn2-eGFP blastocysts, transduced with αMHC-mCherry lentivirus. The mESC expressed markers of pluripotency (Oct3/4; Sox2, Nanog) and differentiated into all three germ layers (Nestin, a-fetoprotein, Brachyury). Cultures differentiated under serum-free, cardiogenic conditions were enriched in cardiomyocytes (n=5), consisting of single positive aMHC-mCherry [57.76±3.7%] and double positive αMHC-mCherry/Cntn2-eGFP cells [1.9±0.9%]. Compared with eGFP negative cardiomyocytes (n=15), double positive cells (n=11) revealed electrophysiological characteristics consistent with Purkinje-like derivatives, including increased peak sodium currents (180.3±20.5 pA/pF vs. =-118.0±21.2pA/pF), faster upstroke velocities (133.7±12.3 V/s vs.60.0±13.2V/s) and elongated action potential duration (APD90=170.2±17.5ms vs. APD90=120.6±17.3ms). Calcium imaging demonstrated chronotrop regulation and spontaneous Ca2+ oscillations in mCherry+eGFP+ cells. Immunofluorecence analysis demonstrated endogenous expression of Purkinje cell markers, including Cntn2, Cx40 and Troponin-T, in double positive cells. Quantitative real-time PCR analysis of double positive cells verified cardiomyocyte-specific transcript expression [Mlc2v: 3.8x106-fold (p&lt;0.05); Nkx2.5: 178-fold (p&lt;0.05) compared to double negative cells]. Moreover, double positive cells expressed significantly elevated levels of CCS-specific transcripts compared to mCherry-single positive cells [Cntn2: 31-fold (p&lt;0.001); Cx40: 878 -fold (p&lt;0.01); Cav3.1: 11-fold (p&lt;0.05); HCN4: 7-fold (p&lt;0.001)]. Conclusion: The dual reporter Purkinje cell mESC reporter line permits identification and enrichment of ventricular CCS derivatives. [Supported by NYSTEM contracts #C024327 and #C028115 to GIF].
Colonisation with toxigenic Corynebacterium diphtheriae in a Scottish burns patient, June 2015
Authors: Ashutosh Deshpande, Teresa Inkster, Kate Hamilton, David Litt, Norman Fry, Iain T R Kennedy, Jacqueline Shookhye-Dickson, Robert L R Hill
Journal: Eurosurveillance (2015)

On 12 June 2015, Corynebacterium diphtheriae was identified in a skin swab from a burns patient in Scotland. The isolate was confirmed to be genotypically and phenotypically toxigenic. Multilocus sequence typing of three patient isolates yielded sequence type ST 125. The patient was clinically well. We summarise findings of this case, and results of close contact identification and screening: 12 family and close contacts and 32 hospital staff have been found negative for C. diphtheriae .
PD6-1-8: 18-FDG-PET based planning of limited stage small cell lung cancer changes radiotherapy fields: A planning study
Authors: Judith v. Loon, Rinus Wanders, Andre Dekker, Monique Hochstenbag, Gerben Bootsma, Geraedts Wiel, Cordula Pitz, Jean Simons, Philippe Lambin, Dirk Ruysscher
Journal: Journal of Thoracic Oncology (2007)
Late-breaking abstract: Repeated bronchoconstriction without additional inflammation is sufficient to induce airway remodelling in asthma
Authors: Christopher Grainge, Jonathan Ward, Gemma Lahiff, Valdeep Dulay, Laurie Lau, Donna Davies, Peter Howarth
Journal: European Respiratory Journal (2011)

Asthma is characterised clinically by intermittent bronchoconstriction and pathologically by structural airway changes termed airway remodelling. Remodelling is associated with adverse long term outcomes and has been attributed to eosinophilic inflammation. In vitro studies suggest that mechanical forces occurring during bronchoconstriction may induce remodelling independent of inflammation. This hypothesis was examined in human volunteers with asthma.   Methods:  48 asthmatics were randomised to 1 of 4 inhalation challenges involving 3 challenges at 48hr intervals: Challenge substances were; allergen (house dust mite), methacholine, saline or salbutamol followed by methacholine. Bronchoalveolar lavage (BAL) and bronchial biopsies were obtained before and 4 days after the challenges.   Results:  Allergen and methacholine challenges induced similar immediate bronchoconstriction. Eosinophilic inflammation increased only in the allergen group (BAL eosinophils (p=0.01), BAL eosinophil cationic protein (p=0.002) and tissue eosinophils (p=0.05)). Markers of remodelling increased in both the allergen and methacholine groups, with no increase in saline or salbutamol/methacholine groups. Sub-basement membrane collagen thickness (p   Conclusions:  Experimentally induced bronchoconstriction without additional airway inflammation is sufficient to induce airway remodelling in asthma.