tbuckley/cabot-search huggingface dataset:
P76 Lentiviral vectors co-expressing hepatitis B core and vFLIP induce potent CD8 T-cell and antibody responses in HLA-A2 transgenic mice
Authors: D Macdonald, N Brindle, M Whelan, M Maini, M Collins, W Rosenberg
Journal: Gut (2010)

Introduction  The failure to clear persistent Hepatitis B viral (HBV) infection is characterised by an insufficient CD8 T-cell response to several antigens including HBV core (HBc). Generating a strong T-cell response to this antigen to counter immunotolerant mechanisms in chronic HBV is an attractive therapeutic strategy. We have previously shown that lentiviral vaccines (LV) encoding antigen can generate potent CD8 and CD4 responses and these can be dramatically enhanced by co-expression of viral FLICE-like inhibitory protein (vFLIP) from Kaposi sarcoma-associated herpes virus. vFLIP is a potent stimulator of the NFKB pathway which matures and activates dendritic cells, enhancing expression of costimulatory molecules (including CD80, CD86 and ICAM1) and increasing IL-12 secretion.  Aim  In this study we aimed to assess CD8 T-cell and antibody responses in HLA-A2 transgenic mice vaccinated with LV co-expressing vFLIP and HBc (A), expressing HBc alone (B) or HBc with an inactive vFLIP mutant (vFLIPa57l) (C).  Method  HLA-A2 transgenic mice were vaccinated with LV 12 days before sacrifice and harvest of splenocytes. These were restimulated overnight with an HLA-A2 restricted HBc peptide (18–27) and/or overlapping HBc peptides. IFN? responses were measured by intracellular cytokine staining and by ELIspot. Antibody responses were assessed by ELISA on serum obtained at sacrifice.  Results  Vaccination with LV co-expressing vFLIP and HBc (A) results in enhanced CD8-T-cell responses compared with mice vaccinated with LV expressing HBc alone (B) or HBc with an inactive vFLIP mutant (vFLIPa57l) (C). This was demonstrated on intracellular cytokine staining for IFN? of CD8+ve splenocytes re-stimulated overnight with HLA-A2 restricted peptide HBc 18–27 (A:B:C=5.35% :1.44% :0.84%). IFN? Elispot demonstrated twofold greater CD8 T-cell responses after restimulation with overlapping HBc peptides in splenocytes from mice vaccinated 12 days previously with LV co-expressing vFLIP and HBc compared with mice vaccinated with LV encoding HBc alone (p=0.006). LV expressing HBc also generated a strong antibody response comparable to vaccination with recombinant protein HBc virus-like particles (VLP). This was despite the presumed endogenous HBc antigen expression in transduced cells and no known mechanism of HBc secretion. LV encoding a mutant HBc p138g which does not multimerise into VLPs failed to raise an antibody response.  Conclusion  LV encoding HBc are a potential means of generating both therapeutic CD8 T-cell and antibody responses in chronic HBV. Our data suggest that an intact VLP structure is essential for the generation of an antibody responses to HBc delivered with a lentiviral platform. We are now using this system to explore potential synergy between T-cell and B-cell responses to HBc in HBV infection.
Immunologic Relatedness of Intracisternal A-Particles in Mouse Embryos and Neoplastic Cell Lines&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: T T Huang, P G Calarco
Journal: JNCI Journal of the National Cancer Institute (1982)

Murine intracisternal A-particles (IAP) are retroviruses expressed in large numbers in certain neoplastic cells and preimplantation mouse embryos. Immuno-electron microscopic detection of IAP-associated antigens in mouse rhabdomyosarcoma cells and early mouse embryos provides the first direct evidence that IAP produced by these two sources are serologically related. In both embryos and cells, data suggest that, after synthesis, IAP core protein rapidly associates with the endoplasmic reticulum. In addition, in embryos only, data confirm earlier observations that IAP-associated antigens are expressed on the cell surface. There is no evidence that the Golgi apparatus is involved in the processing of IAP antigens in either cell type.
The peripheral myelin gene PMP–22/GAS–3 is duplicated in Charcot–Marie–Tooth disease type 1A
Authors: L. J. Valentijn, P. A. Bolhuis, I. Zorn, J. E. Hoogendijk, N. van den Bosch, G. W. Hensels, V. P. Stanton, D. E. Housman, K. H. Fischbeck, D. A. Ross, G. A. Nicholson, E. J. Meershoek, H. G. Dauwerse, G. -J. B. van Ommen, F. Baas
Journal: Nature Genetics (1992)
Induction of Tumors in Hamsters by Rat Rous Sarcoma RBI, Producing Chick Sarcoma Virus. I. Continuous Production of Virus Oncogenic for Chicks by Hamster Sarcoma Cells
Authors: J. Svec, F. Svec, D. Šimkovič, V. Thurzo
Journal: JNCI Journal of the National Cancer Institute (1970)

RBI rat sarcoma cells, producing virus pathogenic for chickens, induced sarcomas in hamsters. These sarcomas were designated RBH. A double heteroinduction, i.e., chicken-rat, rat-hamster, took place. The RBH tumor was transplantable in hamsters. RBH hamster sarcoma cells and virus preparations isolated from them induced sarcomas in chickens. The logarithms of ID50 values were from 1.9–3.7. RBH cells adapted to growth in tissue culture, termed RBHtc, also were transplantable in hamsters. RBHtc cells continuously released a virus infectious to chickens. The chromosomal investigation of RBH and RBHtc cells indicated their hamster origin.
A randomized phase III trial of DX-8951f (Exatecan Mesylate; DX) and Gemcitabine (GEM) vs. Gemcitabine alone in advanced pancreatic cancer (APC)
Authors: E. M. O' Reilly, G. K. Abou-Alfa, R. Letourneau, W. G. Harker, M. Modiano, H. Hurwitz, N. S. Tchekmedyian, J. Ackerman, R. L. De Jager, S. G. Eckhardt
Journal: Journal of Clinical Oncology (2004)

4006 BACKGROUND: DX is a novel hexacyclic, water-soluble, topoisomerase-1 inhibitor. DX has single-agent and combination activity with GEM in APC (D'Adamo, et al. ASCO, 2001; O'Reilly, et al. ASCO, 2002). A multicenter, randomized phase III trial comparing DX + GEM to GEM alone in APC was conducted. METHODS: Eligibility included KPS ≥ 60%; locally advanced or metastatic pancreatic adenocarcinoma; no prior chemotherapy. Radiation (RT) alone for locally advanced disease was permitted. Patients (pts) were randomized on a 1: 1 basis to DX + GEM or GEM alone. Pts were stratified by KPS, 60%, 70–80%, ≥ 90%, locally advanced vs metastatic disease, prior RT vs. no RT. For the DX + GEM arm, DX was dosed at 2.0mg/m2; GEM at 1,000mg/m2 on a days 1 and 8, q 3 weeks. GEM alone was dosed at 1,000mg/m2 up to 7 weeks in the 1st cycle, then weekly x 3, q 4 weeks. Tumor assessment was performed every 6 weeks. The primary endpoint was overall survival. An intent-to-treat analysis was used. An independent data safety monitoring board monitored the trial. RESULTS: From 8/01 to 1/03, 349 patients were randomized, 175 to DX + GEM, and 174 to GEM alone. Twenty-four pts (6.9%) were not treated. The treatment arms were well-balanced for extent of disease, KPS, and prior RT. The median survival time was 6.7 months for DX + GEM and 6.2 months for GEM alone (p=0.52). The median TTP for DX + GEM was 3.7 months and 3.8 months for GEM alone (p=0.22). There was an improvement in time-to-worsening of pain and analgesic consumption for DX + GEM compared to GEM alone. However, time-to-worsening of KPS and weight were similar for both treatment arms. Tumor response rates were 8.2% for DX + GEM and 6.3% for GEM alone. Grade 3–4 toxicity was higher for the DX + GEM arm for neutropenia (30% vs 15%, p=0.001), thrombocytopenia (17% vs 4%, p=0.0004) and vomiting (11% vs 5%, p=0.04). The rates of febrile neutropenia were 4% for DX + GEM and 2% for GEM alone, p=0.24. The relative dose-intensities were similar for both arms: 83% and 81% of projected doses for the DX and GEM arm compared to 92% for GEM alone. CONCLUSIONS: DX + GEM was not superior to GEM alone with respect to overall survival in the front-line treatment of APC. There was a trend in favor of clinical benefit for the combination arm. The results do not alter the standard of care for treatment of APC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi Pharma, Ltd., Daiichi Pharmaceuticals Daiichi Pharmaceuticals Daiichi Pharma, Ltd.
Abstract 13129: Ketogenic Diet Reduces Glucose Uptake and Infarct Volume in Murine Stroke
Authors: Ali Daneshmand, Peiman Habibollahi, Pedram Heidari, Umar Mahmood, Cenk Ayata
Journal: Circulation (2012)

Ischemic penumbra, the hypoperfused but viable tissue at risk surrounding the irreversibly injured core, has been a target for neuroprotective and reperfusion therapies in stroke. Ketogenic diet (K...
The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type of Involvement in the Forthcoming Eighth Edition of the TNM Classification
Authors: Frank C. Detterbeck, Edith M. Marom, Douglas A. Arenberg, Wilbur A. Franklin, Andrew G. Nicholson, William D. Travis, Nicolas Girard, Peter J. Mazzone, Jessica S. Donington, Lynn T. Tanoue, Valerie W. Rusch, Hisao Asamura, Ramón Rami-Porta, Peter Goldstraw, Ramón Rami-Porta, Hisao Asamura, David Ball, David G. Beer, Ricardo Beyruti, Vanessa Bolejack, Kari Chansky, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, Jeremy Erasmus, Douglas Flieder, Myrna Godoy, Jin Mo Goo, Lawrence R. Goodman, Jim Jett, Paul de Leyn, Alberto Marchevsky, Heber MacMahon, David Naidich, Morohito Okada, Marina Perlman, Charles Powell, Paul van Schil, Ming S. Tsao, Arne Warth
Journal: Journal of Thoracic Oncology (2016)
Acute exacerbation in COPD: we must do more
Authors: Tobias Welte
Journal: European Respiratory Journal (2015)

If one asks medical students which emergencies they hold as especially important in internal medicine, more than 90% first mention myocardial infarction and stroke. This is not surprising, because these diseases occupy the first places in the mortality statistics contained in the Global Burden of Disease report [1]. Nevertheless, respiratory failure is only described as rare, despite the fact that chronic obstructive pulmonary disease (COPD) is ranked fifth and pneumonia seventh in the same report. While the high hospital mortality rate of myocardial infarction and stroke is well known, the risk of acute exacerbation of COPD and of pneumonia is often underestimated. COPD audit: COPD exacerbation and pneumonia are internal medicine emergencies needing treatment in specialist units <http://ow.ly/VgjSS>
Alternating sequential endocrine therapy: Tamoxifen and medroxyprogesterone acetate versus tamoxifen in postmenopausal advanced breast cancer patients
Authors: M Beltrán, M C Alonso, M B Ojeda, A Izquierdo, J Ferrer, C Picó, L Anglada, G Catalán, E Batiste-Alentorn, I Tusquets
Journal: Annals of Oncology (1991)
Evidence on Use of Neuroimaging for Surgical Treatment of Temporal Lobe Epilepsy
Authors: Amy L. Jones, Gregory D. Cascino
Journal: JAMA Neurology (2016)

Surgery is an effective treatment for drug-resistant focal epilepsy. Neuroimaging studies are considered essential in the diagnostic evaluation of individuals with medically refractory focal seizures being considered for surgical treatment.To review the evidence for the use of neuroimaging studies in the selection of patients with drug-resistant temporal lobe epilepsy for focal cortical resection and discuss the prognostic importance of selected techniques.Randomized clinical trials, meta-analyses, and clinical retrospective case studies (≥20 patients with ≥1 year of follow-up) were identified using Medical Subject Headings and indexed text terms in EMBASE (1988-November 29, 2014); MEDLINE (1946-December 2, 2014), Cochrane Central Register of Controlled Trials (1991-October 31, 2014), and Cochrane Database of Systematic Reviews (2005-October 31, 2014). Twenty-seven articles describing 3163 patients were included. Neuroimaging techniques analyzed included magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Subpopulations and prognostic factors were identified.Of the 27 studies evaluated (3163 patients), 7 showed the outcome was more favorable in patients with MRI-identified hippocampal atrophy indicating mesial temporal sclerosis. Five additional studies indicated that the outcome was less favorable in patients with unremarkable MRI studies. There are conflicting findings regarding the prognostic importance of PET-identified focal hypometabolism; however, 2 investigations indicated that the presence of a PET imaging study demonstrating abnormalities in individuals with unremarkable MRI results showed an operative outcome similar to that in patients with mesial temporal sclerosis. The studies assessing SPECT use in temporal lobe epilepsy did not reveal a correlation with outcome.There is strong evidence that preoperative MRI-identified hippocampal atrophy consistent with mesial temporal sclerosis concordant with the seizure origin in the temporal lobe is a significant factor associated with a favorable outcome. PET studies may be valuable in individuals with unremarkable MRI findings. The current evidence does not support the prognostic importance of SPECT in patients undergoing temporal lobe surgery.
LBA-03 Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072)
Authors: D. Cunningham, R. Langley, M. Nankivell, J. Blazeby, M. Griffin, A. Crellin, H. Grabsch, A. Okines, C. Goldstein, S. Falk, J. Thompson, R. Krysztopik, F. Coxon, S. Pritchard, R. Langer, S. Stenning, D. Alderson
Journal: Annals of Oncology (2015)
Response to Letter Regarding Article, “Clinical Impact of Contemporary Cardiovascular Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy”
Authors: Martin S. Maron, Barry J. Maron
Journal: Circulation (2016)

We appreciate the comments by Ferreira et al regarding our recent Clinician Update on the clinical impact of cardiovascular magnetic resonance (CMR) in hypertrophic cardiomyopathy (HCM). 1 We agree completely with the authors that the diagnosis and clinical management of patients with this complex genetic heart disease has been substantially enhanced by applying CMR to large consecutive cohorts of this disease over the past 10 years.Indeed, CMR is ideally suited to defining the diverse HCM phenotype 2 by providing images with high spatial resolution, sharp contrast between the myocardial border and blood pool (permitting more reliable left ventricular wall thickness measurements than is possible with echocardiography in some patients), 2 and visualization of all left ventricular segments without obliquity.In addition, contrast-enhanced CMR with late gadolinium enhancement has the capability of identifying areas of myocardium occupied by fibrosis/scarring, information not obtainable with echocardiography.In this regard, CMR has become part of the HCM risk stratification algorithm, identifying candidates for implantable defibrillators and prevention of sudden death, even in the absence of conventional risk markers. 3These imaging strengths of CMR have resulted in improved diagnosis and risk prediction, thereby introducing into cardiovascular practice a new era of imaging for HCM.We therefore agree with an expanded role for CMR in HCM, to be performed at least once as part of the contemporary assessment of all patients with a confirmed (or suspected) HCM diagnosis.5] In addition, despite historical differences in the approach to certain aspects of HCM management among investigators in the United States and Europe, we are pleased to see that the importance of CMR in HCM has emerged as an area of common ground independent of the national origin of the clinical imagers.We are hopeful that this mutual enthusiasm and support will help facilitate future investigations aimed at improving our understanding of how CMR can further impact clinical management strategies for patients with HCM.
How to do it: How to acquire a coat of arms
Authors: J. Thurston
Journal: BMJ (1997)

The Faculty of Accident and Emergency Medicine was inaugurated on 2 November 1993. The new council decided that it would like a logo or badge to signify its identity and to adorn such items as headed notepaper and the president's badge of office. As registrar I was instructed to approach the College of Arms for letters-patent granting the faculty its own coat of arms.

Because of the multidisciplinary nature of accident and emergency medicine, the faculty is an intercollegiate one based on six royal colleges. The faculty has flourished, it has a steadily increasing membership, and the faculty board's examination committee holds regular examinations for fellowship of the faculty twice a year.

The first step was to approach the College of Arms in London and the duty herald, who in our case was William Hunt, Portcullis Pursuivant of Arms. He led me through the detailed process of acquiring our armorial bearings.

We submitted the articles of constitution of the faculty to Portcullis, who submitted them to the Kings of Arms. The faculty was then given permission to petition the Earl Marshal for armorial bearings. Portcullis had made it clear that the smaller the committee designing the coat of arms the better. He favoured a committee of one. In the event we formed a small subcommittee of three.

Figure 1 shows the principal elements of an achievement of arms, in this case those of the Worshipful …
Virological and Immunological Features of Long-Term Human Immunodeficiency Virus–Infected Individuals Who Have Remained Asymptomatic Compared With Those Who Have Progressed to Acquired Immunodeficiency Syndrome
Authors: Edward Barker, Carl E. Mackewicz, Gustavo Reyes-Terán, Akihiko Sato, Sharon A. Stranford, Sue H. Fujimura, Cindy Christopherson, Sheng-Yung Chang, Jay A. Levy
Journal: Blood (1998)
SAT0238 The cost of osteoarthritis and its association with the severity of the disease
Authors: A Belisari, LG Mantovani
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To assess the cost related to caring for Osteoarthritis (OA) patients in Italy and to verify any association between cost and severity expressed in terms of Lequesne Index (LI) score. <h3>Methods</h3> The analytic framework of the present study was a prevalence-based Cost of Illness Analysis. The societal perspective was adopted with a 6 months time horizon. Subjects: Eleven rheumatologic centres were selected all over Italy. These recruited and interviewed the first 30 consecutive OA patients presenting to their office with a diagnosis of knee osteoarthritis. To this purpose, a questionnaire was developed so to collect information about: demography, concomitant localisation of OA, LI score, direct and indirect costs. The severity of the disease was assessed at the time of the visit. To investigate the association between cost and severity we used multivariate linear regression techniques. <h3>Results</h3> A total of 277 patients were recruited and interviewed. The average age was 65,7 (± 9,8) years, the average LI score was 12,3 (± 4,5) and the 73% were female subjects. In 6 months the burden to society to care for an OA patient was around 1.993 Euro (year 2000 value). Almost 33% of this cost was represented by direct costs and about 67% by indirect costs. In general, the most important component of cost was informal care, followed by productivity losses and direct medical cost. Statistical analysis: The total cost was significantly associated with disease severity (p &lt; 0,001), increasing with increasing severity as measured through LI quartiles. <h3>Conclusion</h3> From our results, it appears that interventions reducing LI score are likely to reduce the amount of resources needed to care for OA patients.
Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system
Authors: Karen A. Simon, Bobak Mosadegh, Kyaw Thu Minn, Matthew R. Lockett, Marym R. Mohammady, Diane M. Boucher, Amy B. Hall, Shawn M. Hillier, Taturo Udagawa, Brenda K. Eustace, George M. Whitesides
Journal: Biomaterials (2016)
The Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs
Authors: Patrick Micke, Johanna Sofia Margareta Mattsson, Dijana Djureinovic, Björn Nodin, Karin Jirström, Lena Tran, Per Jönsson, Maria Planck, Johan Botling, Hans Brunnström
Journal: Journal of Thoracic Oncology (2016)
Letter by Ferreira et al Regarding Article, “Clinical Impact of Contemporary Cardiovascular Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy”
Authors: António Ferreira, Hugo Marques, Nuno Cardim
Journal: Circulation (2016)

We read with enthusiasm the Clinician Update from Maron and Maron 1 on the role of cardiac magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM).It was a great pleasure to see that, in this regard, there is full agreement on the viewpoints of European and US cardiologists.In fact, in 2 recently published articles from European institutions, CMR is recommended for all HCM patients in the absence of contraindications. 2,3In the 2015 European Association of Cardiovascular Imaging Expert Consensus document, this indication is highlighted as a key point: "CMR should be considered in all HCM patients: It should be performed at least once-at the initial evaluation-if local resources and expertise permit, and may be repeated according to potential changes in the clinical status, in order to answer to specific clinical questions and problems." 2 In the 2014 European Society of Cardiology guidelines this comes as a class IIa recommendation, level of evidence B: "In the absence of contraindications, CMR with late gadolinium enhancement (LGE) should be considered in patients fulfilling diagnostic criteria for HCM, to assess cardiac anatomy, ventricular function, and the presence and extent of myocardial fibrosis." 3s the authors appropriately state, the role of CMR in HCM spans from diagnosis and family screening to prognostic assessment and preprocedural planning for septal reduction.Arguably, in the near future, the most useful piece of information provided by CMR will likely be the amount of myocardial delayed enhancement to refine the assessment of sudden cardiac death risk. 4Of course, a lot still needs to be done to bridge the gap between recommendations and clinical practice, and to further substantiate the usefulness of CMR with studies that prove its impact in clinical decision making and, most importantly, patient outcomes.Nevertheless, it is with great pleasure that we realize that, thanks to CMR, the HCM recommendations distance between the United States and Europe is becoming shorter.
A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma
Authors: K.J. O'Byrne, P.A. Philip, D.J. Propper, I.P. Braybrooke, M.P. Saunders, N.P. Bates, M.A. Taylor, D. Madigan, T.S. Ganesan, D.C. Talbot, A.L. Harris
Journal: Annals of Oncology (1999)