tbuckley/cabot-search huggingface dataset:
Abstract 2532: Integrated therapeutic antibody development at the National Research Council of Canada
Authors: Maria Luz Jaramillo, Maureen O'Connor-McCourt
Journal: Cancer Research (2012)

Abstract Advances in genomics and antibody engineering have enabled the development of an innovative class of targeted therapies to provide new treatment options for diseases with significant unmet medical needs such as cancer. Therapeutic antibodies represent one of the fastest growing classes of medications with sales anticipated to exceed $30 billion globally by 2012. The NRC has built a chain of cutting edge technology platforms needed to discover, engineer and produce therapeutic monoclonal antibodies with the goal of partnering with industrial and academic centers to advance research and development of this important class of therapeutics. Target Identification- To establish and validate the technology platform, tumor targets for candidate therapeutic antibody production were identified using a combination of proteomics, transcriptomics and bioinformatic approaches. Out of these lists, approximately 40 tumor targets were selected (known therapeutic antibody targets were excluded), and over 2,000 antibodies of mouse and camelid origin were then generated against these targets. Antibody generation- Once identified, the recombinant target protein of interest can be produced using the NRC's high efficiency cell expression platforms in CHO or HEK293 cells and purified protein used for immunization or panning. For targets which are difficult to express or purify, the capabilities for direct immunization with plasmid DNA constructs provides another option. Clone selection is carried out by ELISA and typically 50 antibodies/target are identified for further characterization. Antibody characterization and validation- The affinities of the antibodies are determined by SPR biosensor analysis. Reverse phase protein arrays and Western blot analysis on protein mixes and cell lines allow the characterization of the specificity of the antibodies. Epitope mapping can be carried out so that representative antibodies from each epitope bin can be selected for further validation in appropriate cell-based assays (many of which are established at NRC) and animal models. Therapeutic antibody Optimization, Bioprocessing and Biomanufacturing- Therapeutic antibodies selected for development can be further optimized using antibody engineering technologies to humanize them and/or modify their glycosylation patterns to improve their effector function, pharmacokinetics, solubility and stability as well as reduce their immunogenicity. The NRC platform for large scale protein production has the capacity to manufacture up to 13.5 g of commercial grade antibody using serum free, low endotoxin media in a cGMP certified CHO cell line which is ready for transfer to CMOs or other industrial partners. 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 2532. doi:1538-7445.AM2012-2532
Case 32-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Gerald F. Winkler, Suzanne M. de la Monte
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 69-year-old woman was admitted to the hospital because of multiple cranial-nerve palsies and weakness of the legs.She was well and active until seven months earlier, when she experienced the sudden onset of right lower facial weakness, which was believed to be Bell's palsy. Prednisone was administered, without improvement. During the four months to two months before admission the facial weakness became bilateral, and evidence of bilateral trigeminal-nerve and acoustic-nerve palsies developed, accompanied by difficulty in walking, diffuse weakness of the lower extremities, impaired phonation, and a decreased gag reflex.The patient was seen at two . . .
Representation and Misrepresentation of Scientific Evidence in Contemporary Tobacco Regulation: A Review of Tobacco Industry Submissions to the UK Government Consultation on Standardised Packaging
Authors: Selda Ulucanlar, Gary J. Fooks, Jenny L. Hatchard, Anna B. Gilmore
Journal: PLoS Medicine (2014)

Standardised packaging (SP) of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs) whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for 'more evidence', but four months later a second 'independent review' was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP.We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, 'mimicked scientific critique' was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific) model, and was not rigorous. Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach.The TTCs' claim that SP will not lead to public health benefits is largely without foundation. The tools of Better Regulation, particularly stakeholder consultation, provide an opportunity for highly resourced corporations to slow, weaken, or prevent public health policies.
Impairment of heart rate variability control during arsenic trioxide treatment for acute promyelocytic leukemia
Authors: A Takeshita, A Uehara, K Shinjo, K Naito, N Sahara, K Yamazaki, H Katoh, T Kamikawa, K Ohnishi, M Maekawa, H Hayashi, R Ohno
Journal: Leukemia (2003)
Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene.
Authors: M J Telen, G S Eisenbarth, B F Haynes
Journal: Journal of Clinical Investigation (1983)

Our study describes a novel human erythrocyte protein antigen, the expression of which is regulated by the rare Lutheran inhibitor In(Lu) gene. We have produced a monoclonal antibody (A3D8) that bound strongly to erythrocytes from subjects with Lutheran phenotypes Lu(a+b+), Lu(a+b-), and Lu(a-b+) but bound negligibly to erythrocytes from subjects with the dominant form of Lu(a-b-) phenotype, reflecting inheritance of the In(Lu) gene. Importantly, erythrocytes from an individual with the recessive form of Lu(a-b-) phenotype (i.e., absence of the In(Lu) gene and absence of genes encoding for Lutheran antigens) showed reactivity with A3D8 antibody comparable to that seen with Lu(a+) or Lu(b+) erythrocytes. A3D8 antigen activity was also found on all leukocytes and in serum and plasma; this activity also appeared to be regulated by the In(Lu) gene in serum, plasma, and on a subset of leukocytes. Thus, we have identified a human erythrocyte protein whose expression is modified by the In(Lu) gene. This knowledge that such an antigen exists on erythrocytes and in normal plasma should allow further studies into the molecular genetics of the In(Lu) gene and into the functional and structural significance of the A3D8 antigen.
The Steve Biko case: politics and medical ethics
Authors: J N De Klerk
Journal: BMJ (1980)

expertise.There may need to be some change of emphasis with the increased importance which attaches to lay management, but I personally doubt it.What then of our hypothetical medical superintendent ?So far as the actual appointment is concerned I have no doubt of the need, but see the main difficulty to be in getting somebody to sit down and formulate the position, status, qualifications, accountability, and responsibilities of such an individual and of his relationship to the lay staff with whom he will have to operate if he is to be effective in translating policy into fact and medical opinion into reality.
Abstract 4235: Notch ligand-dependent cancer stem cell niche in glioblastoma
Authors: Thant S. Zhu, Shawn Hervey-Jumper, Francesco DiMeco, Angelo L. Vescovi, Jason A. Heth, Karin M. Muraszko, Xing Fan
Journal: Cancer Research (2010)

Abstract Recent data shows that endothelial cells function as a stem cell niche to promote CD133-positive cancer stem-like cells (CSLCs) self-renewal in glioblastoma (GBM). However, the mechanism by which endothelial cells function as a stem cell niche is largely unknown. To test if endothelial cells and differentiated tumor cells could function as a niche by providing Notch ligands to CSLCs, first we co-cultured GBM neurospheres with primary human endothelial cells (PHECs) which express Notch ligand Jagged/Delta. We found that PHECs promote GBM neurosphere growth, CD133 expression and clonogenicity in vitro, whereas knocking down Notch ligand expression in PHECs abrogates PHEC-induced GBM growth. We also found that the CD133-negative GBM cells express a higher level of Jagged/Delta and glial differentiation marker GFAP compared with CD133-positive population. When GBM neurospheres were forced to differentiate and grow as mono-layer attached cells, CD133-positive population was reduced, whereas expression of GFAP (glial marker), GalC (oligodendrocyte marker), Tuj1 (neuronal marker) and Notch ligands were induced. Furthermore, treatment of GBM neurospheres with a Jagged peptide increases GBM growth in a dosage dependent fashion. In addition, Notch ligands are highly expressed in the blood vessels of GBM primary tumors and intracranial xenografts in mouse, and CSLCs accumulate around the blood vessels within the tumors. Finally, we found that knocking down Notch ligands in PHECs inhibits GBM xenograft propagation in mice through reducing CD133-positive population. In summary, we show that Notch activation in GBM CSLCs is driven by juxtacrine signaling between tumor cells replicating the classical process of lateral inhibition and by stromal niche signals, suggesting that targeting both CSLCs and their niche may provide a profound strategy to deplete GBM CSLCs. 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 4235.
Two tests may be better than one in bowel cancer screening, finds study
Authors: N. Hawkes
Journal: BMJ (2012)

Two sigmoidoscopy tests separated by three to five years detect roughly a third more bowel cancers than does a single test, a new study shows. But whether the benefit of detecting the extra cancers justifies the additional costs and the risks of complications, or whether it reduces mortality by a similar degree, remains unknown.

The NHS in England plans to offer flexible sigmoidoscopy screening for bowel cancer to all people from the age of 55, after a trial showed that a single such test conferred a substantial and lasting benefit. The new results, from …
Eye inflammation in psoriatic arthritis.
Authors: J R Lambert, V Wright
Journal: Annals of the Rheumatic Diseases (1976)

In a study of 112 patients (49 men, 63 women) with psoriatic arthritis, ocular inflammation was noted in 35 (31.2%). Conjunctivitis was the most common lesion, being found in 19.6% (10 males, 12 females). Iritis occurred in 7.1% (5 men, 3 women), episcleritis in 1.8% (1 man, 1 woman), and keratoconjunctivitis sicca in 2.7% (3 women). 20 patients (10 men, 10 women) had radiological sacroiliitis and 11 of these (7 men, 4 women) had ankylosing spondylitis according to the New York criteria. Eye lesions were noted in 7 of the patients with sacroiliitis, 3 having iritis (15%) and 4 (20%) conjunctivitis. 2 patients with spondylitis had iritis (18%) and 1 (9%) conjunctivitis. It is concluded that inflammatory eye lesions are a frequent accompaniment to psoriatic arthritis. This is taken as further evidence for the concept of the seronegative spondyloarthritides.
Gruppenpsychotherapie und Symbolbildung
Authors: W. Willeford
Journal: Psychotherapy and Psychosomatics (1966)

Research Articles| February 11 2010 Gruppenpsychotherapie und Symbolbildung Subject Area: Psychiatry and Psychology W. Willeford W. Willeford Klinik am Zürichberg der Stiftung «Klinik und Forschungsstätte für Jungsche Psychologie », Zürich (Chefarzt: Dr. med. H. K. Fierz) Search for other works by this author on: This Site PubMed Google Scholar Psychother Psychosom (1966) 14 (4): 282–297. https://doi.org/10.1159/000285831 Article history Published Online: February 11 2010 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation W. Willeford; Gruppenpsychotherapie und Symbolbildung. Psychother Psychosom 1 April 1966; 14 (4): 282–297. https://doi.org/10.1159/000285831 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsPsychotherapy and Psychosomatics Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1966Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
Family Consent to Orders Not to Resuscitate
Authors: David J. Doukas
Journal: JAMA (1991)

<h3>To the Editor. —</h3> Hackler and Hiller's<sup>1</sup>recent article addressing the need to reconsider hospital resuscitation policies was valuable in furthering the exchange of ideas on the "futility" of treatment. In the same issue, Tomlinson and Brody<sup>2</sup>also argue for the limiting of resuscitative efforts in the face of futility. However, the two points of view diverge at the important point of informing the patient or the incompetent patient's family that medical therapies would be clearly fruitless. Tomlinson and Brody, as well as Youngner<sup>3</sup>in a commentary on both articles, encourage discussion on the futility of therapy with the patient and family for a variety of reasons, such as facing denial of death. In contrast, Hackler and Hiller's first proposal states that "hospital policy should allow physicians to write DNR orders without family [or patient] consent or discussion, if CPR would be futile."1 However, even when treatment
Isolation of a human myocardial cytosolic phospholipase A2 isoform. Fast atom bombardment mass spectroscopic and reverse-phase high pressure liquid chromatography identification of choline and ethanolamine glycerophospholipid substrates.
Authors: S L Hazen, C R Hall, D A Ford, R W Gross
Journal: Journal of Clinical Investigation (1993)

Recent studies have demonstrated the existence of a novel family of calcium-independent plasmalogen-selective phospholipases A2 in canine myocardium that have been implicated as enzymic mediators of ischemic membrane damage. We now report that human myocardium contains two functionally distinct isoforms of cytosolic calcium-independent phospholipase A2. The major cytosolic phospholipase A2 isoform preferentially hydrolyzes plasmalogen substrate, possesses a pH optimum of 7.0, and is chromatographically resolvable from a minor cytosolic calcium-independent phospholipase A2 isoform that hydrolyzes plasmenylcholine and phosphatidylcholine substrates at similar rates and possesses a pH optimum of 8.5. The major cytosolic calcium-independent phospholipase A2 isoform was identified as a 40-kD polypeptide after its 182,000-fold purification by sequential column chromatographies to a final specific activity of 67 mumol/mg.min. The purified 40-kD human myocardial phospholipase A2 preferentially hydrolyzes plasmalogens containing arachidonic acid at the sn-2 position. Both reverse-phase HPLC and fast atom bombardment mass spectroscopic analysis of human myocardial ethanolamine and choline glycerophospholipids demonstrated that plasmenylethanolamine and plasmenylcholine molecular species containing arachidonic acid at the sn-2 position are prominent constituents of human myocardium. Collectively, these results identify and characterize the major human myocardial cytosolic calcium-independent phospholipase A2 activity, demonstrate the presence of functionally distinct human myocardial cytosolic calcium-independent phospholipase A2 isoforms, and document the abundance of arachidonoylated plasmalogen molecular species in human myocardium that serve as substrates.
Pseudomonas infection caused by bronchoscope manufacturing defects: effective national recall procedures are needed
Authors: Z Hall
Journal: Thorax (2003)

▴ Srinivasan A, Wolfenden LL, Song X, et al . An outbreak of Pseudomonas aeruginosa infections associated with flexible bronchoscopes. N Engl J Med2003;348:221–7 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This study investigated the source of a Pseudomonas aeruginosa outbreak associated with flexible bronchoscopes that occurred at the Johns Hopkins Hospital, Baltimore, USA from June 2001 to January 2002 and compared it with an 11 … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DSrinivasan%26rft.auinit1%253DA.%26rft.volume%253D348%26rft.issue%253D3%26rft.spage%253D221%26rft.epage%253D227%26rft.atitle%253DAn%2BOutbreak%2Bof%2BPseudomonas%2Baeruginosa%2BInfections%2BAssociated%2Bwith%2BFlexible%2BBronchoscopes%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa021808%26rft_id%253Dinfo%253Apmid%252F12529462%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa021808&link_type=DOI [3]: /lookup/external-ref?access_num=12529462&link_type=MED&atom=%2Fthoraxjnl%2F58%2F4%2F332.atom [4]: /lookup/external-ref?access_num=000180390600006&link_type=ISI
Abstract 1337: MUC1 facilitates BPDE-induced EGFR activation and malignant transformation in human bronchial epithelial cells
Authors: Xiuling Xu, Lang Bai, Wenshu Chen, Zi Li, Kwang Chul Kim, Steven A. Belinsky, Yong Lin
Journal: Cancer Research (2011)

Abstract Inflammation has emerged as an important factor for the development of lung cancer. However, the gene targets and pathways that are involved in inflammation-associated lung cancer development have not been clearly elucidated. Cigarette smoke (CS), which causes chronic pulmonary inflammation, is an established risk factor for lung cancer. MUC1 (MUC in human and Muc in animals), a mucin-like glycoprotein expressed on the surface of airway epithelial cells, is inducible during lung inflammation. MUC1 is also overexpressed as a tumor antigen in lung tumors. We found that chronic CS exposure significantly increased Muc1 expression in mouse airway epithelial cells associated with infiltration of inflammatory cells to the lung. The role of MUC1 in lung epithelial cell transformation induced by benzo[a]pyrene diol epoxide (BPDE), the active form of the CS carcinogen benzo(a)pyrene (BaP), was examined in an in vitro cell transformation assay. Knockdown of MUC1 by shRNA significantly reduced the efficacy of BPDE-induced transformation of BEAS-2B, an SV40 large T antigen immortalized human bronchial epithelial cell line. BPDE strongly activated EGFR and Akt in BEAS-2B cells. Akt activation was blocked with an EGFR inhibitor, suggesting that BPDE activates the EGFR/Akt cascade. Blocking this cascade with inhibitors for either EGFR or Akt significantly inhibited BPDE-induced cell transformation, supporting a critical role for EGFR and Akt activation in BPDE-induced cell transformation. Interestingly, the BPDE-induced activation of EGFR and Akt was attenuated when MUC1 expression was knocked down. Suppression of EGFR or Akt significantly increased BPDE's cytotoxicity. Consistently, the MUC1-suppressed BEAS-2B cells were more sensitive to BPDE-induced death. Taken together, these results suggest that MUC1 plays an oncogenic role in the early stages of inflammation-associated lung cancer development, at least partly through mediating carcinogen-induced activation of the EGFR/Akt pathway that potentiates survival in immortalized bronchial epithelial cells. This work is supported by 1R01ES017328. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1337. doi:10.1158/1538-7445.AM2011-1337