tbuckley/cabot-search huggingface dataset:
Abstract SY19-02: Role of the Tim-3 and PD-1 pathways in T cell exhaustion and antitumor immunity
Authors: Ana C. Anderson
Journal: Cancer Research (2011)

Abstract The immune response plays an important role in fighting cancer; however, mechanisms of immune suppression in tumor-bearing hosts hinder productive antitumor immunity. T cell dysfunction or exhaustion is one such mechanism. PD-1 has been identified as a marker of dysfunctional or exhausted T cells in chronic disease states and blockade of PD-1/PD-1L interactions has been shown to partially restore T cell function. Recently, Tim-3 has also been identified as a marker of exhausted T cells. We have found that Tim-3 is expressed on both CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) in mice bearing solid tumors (4T1, CT26, and B16). All CD8+ Tim-3+ TILs co-express PD-1 and Tim-3+PD-1+ TILs represent a predominant fraction of the CD8+ T cells infiltrating tumors. CD8+Tim-3+PD-1+ TILs exhibit the most severe exhausted phenotype as defined by failure to proliferate, produce IL-2, TNFα and IFNγ. We have further found that combined immunotherapeutic targeting of the Tim-3 and PD-1 pathways is more effective in controlling tumor growth than targeting either pathway alone. Indeed, 50% of the mice receiving combination immunotherapy exhibited complete tumor regression. We have examined whether combined targeting of Tim-3 and PD-1 restores effector function to TILs and have found that culture of TILs in vitro in the presence of anti-Tim-3 plus anti-PD-L1 antibodies augments IFNγ production. In addition, T cells isolated from the tumor-draining lymph nodes of mice treated in vivo with anti-Tim-3 and anti-PD-L1 antibodies exhibit restored tumor antigen-specific T cell responses compared to those isolated from mice treated with control immunoglobulins. Collectively, our data support that combined targeting of the Tim-3 and PD-1 signaling pathways is highly effective in restoring antitumor immunity. 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 SY19-02. doi:10.1158/1538-7445.AM2011-SY19-02
Randomized placebo controlled double blind study in patients with chronic hepatitis C who did not respond to interferon therapy: Comparison between interferon A, ribavirin +/- amantadine
Authors: M. Schories, B. Kallinowski, T. Goeser, K.P. Maier, A. Lutterer, V. Wietzke-Braun, J. Rasenack
Journal: Journal of Hepatology (2003)
Abstract 5156: The oncogenic polycomb histone methyltransferase EZH2 methylates lysine 120 on histone H2B and competes ubiquitination in human cancer
Authors: Ryuji Hamamoto, Yusuke Nakamura
Journal: Cancer Research (2014)

Abstract The histone methyltransferase EZH2 is known to be a polycomb protein homologus to Drosophila enhancer of zeste and catalyzes the addition of methyl groups to histone H3 at lysine 27 (H3K27). We previously reported that EZH2 was overexpressed in various types of cancer and plays a crucial role in the cell cycle regulation of cancer cells. In this study, we demonstrated that EZH2 has the function to mono-methylated lysine 120 on histone H2B (H2BK120). EZH2-dependent H2BK120 methylation in cancer cells was confirmed with an H2BK120 methylation-specific antibody. Overexpression of EZH2 significantly attenuated the ubiquitination of H2BK120, a key post-translational modification of histones for transcriptional regulation. Concordantly, knockdown of EZH2 increased the ubiquitination level of H2BK120, suggesting that the methylation of H2BK120 by EZH2 may competitively inhibit the ubiquitination of H2BK120. Subsequent ChIP-Seq and microarray analyses identified downstream candidate genes regulated by EZH2 through the methylation of H2BK120. This is the first report to describe a novel substrate of EZH2, H2BK120, unveiling a new aspect of EZH2 functions in human carcinogenesis. Citation Format: Ryuji Hamamoto, Yusuke Nakamura. The oncogenic polycomb histone methyltransferase EZH2 methylates lysine 120 on histone H2B and competes ubiquitination in human cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5156. doi:10.1158/1538-7445.AM2014-5156
Role of nosocomial hospital transmission in acute hepatitis C: Reply
Authors: Xavier Forns
Journal: Journal of Hepatology (2008)

To the Editor:We agree with most of the comments made by Morin and colleagues [[1]Morin T. Pariente A. Cadranel J-F. Denis J. Role of nosocomial hospital transmission in acute hepatitis C.J Hepatol. 2009; 50: 214Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. As we stated in our manuscript [[2]Martinez- Bauer E. Forns X. Armelles M. Palas R. Sola R. Vergara M. et al.Hospital admission is a relevant cause of hepatitis C virus acquisition in Spain.J Hepatol. 2008; 48: 20-27Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar], the inclusion of two HCV infection outbreaks and the fact that most cases were referred to tertiary care centers might certainly represent a bias in our cohort. Nevertheless, we believe that nosocomial HCV transmission occurs in all regions, due to the fact that adherence to universal precautions is not regularly stressed in health care centers. If the authors exclude intravenous drug abuse in their prospective study, nosocomial HCV acquisition would be responsible for one-third of the cases of acute hepatitis C. Thus, in patients who deny drug abuse, nosocomial acquisition is most likely to be the first cause of acute HCV infection. With our article, we wanted to stress the relevance of this mode of transmission and the need for regular epidemiological investigations into cases where nosocomial HCV transmission is suspected. To the Editor: We agree with most of the comments made by Morin and colleagues [[1]Morin T. Pariente A. Cadranel J-F. Denis J. Role of nosocomial hospital transmission in acute hepatitis C.J Hepatol. 2009; 50: 214Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. As we stated in our manuscript [[2]Martinez- Bauer E. Forns X. Armelles M. Palas R. Sola R. Vergara M. et al.Hospital admission is a relevant cause of hepatitis C virus acquisition in Spain.J Hepatol. 2008; 48: 20-27Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar], the inclusion of two HCV infection outbreaks and the fact that most cases were referred to tertiary care centers might certainly represent a bias in our cohort. Nevertheless, we believe that nosocomial HCV transmission occurs in all regions, due to the fact that adherence to universal precautions is not regularly stressed in health care centers. If the authors exclude intravenous drug abuse in their prospective study, nosocomial HCV acquisition would be responsible for one-third of the cases of acute hepatitis C. Thus, in patients who deny drug abuse, nosocomial acquisition is most likely to be the first cause of acute HCV infection. With our article, we wanted to stress the relevance of this mode of transmission and the need for regular epidemiological investigations into cases where nosocomial HCV transmission is suspected.
Cyclin-A1 represents a new immunogenic targetable antigen expressed in acute myeloid leukemia stem cells with characteristics of a cancer-testis antigen
Authors: Sebastian Ochsenreither, Ravindra Majeti, Thomas Schmitt, Derek Stirewalt, Ulrich Keilholz, Keith R. Loeb, Brent Wood, Yongiae E. Choi, Marie Bleakley, Edus H. Warren, Michael Hudecek, Yoshiki Akatsuka, Irving L. Weissman, Philip D. Greenberg
Journal: Blood (2012)
Integrating Mental Health and Development: A Case Study of the BasicNeeds Model in Nepal
Authors: Shoba Raja, Chris Underhill, Padam Shrestha, Uma Sunder, Saju Mannarath, Sarah Kippen Wood, Vikram Patel
Journal: PLoS Medicine (2012)

As one article in a series on Global Mental Health Practice, Shoba Raja and colleagues provide a case study of BasicNeeds in Nepal, which emphases user empowerment, community development, health systems strengthening, and policy change to help socially disadvantaged individuals with mental health conditions.
Combined Inhibition of CCL2, CX3CR1, and CCR5 Abrogates Ly6C <sup>hi</sup> and Ly6C <sup>lo</sup> Monocytosis and Almost Abolishes Atherosclerosis in Hypercholesterolemic Mice
Authors: Christophe Combadière, Stéphane Potteaux, Mathieu Rodero, Tabassome Simon, Adeline Pezard, Bruno Esposito, Régine Merval, Amanda Proudfoot, Alain Tedgui, Ziad Mallat
Journal: Circulation (2008)

Background— Monocytes are critical mediators of atherogenesis. Deletion of individual chemokines or chemokine receptors leads to significant but only partial inhibition of lesion development, whereas deficiency in other signals such as CXCL16 or CCR1 accelerates atherosclerosis. Evidence that particular chemokine pathways may cooperate to promote monocyte accumulation into inflamed tissues, particularly atherosclerotic arteries, is still lacking. Methods and Results— Here, we show that chemokine-mediated signals critically determine the frequency of monocytes in the blood and bone marrow under both noninflammatory and atherosclerotic conditions. Particularly, CCL2-, CX3CR1-, and CCR5-dependent signals differentially alter CD11b + Ly6G − 7/4 hi (also known as Ly6C hi ) and CD11b + Ly6G − 7/4 lo (Ly6C lo ) monocytosis. Combined inhibition of CCL2, CX3CR1, and CCR5 in hypercholesterolemic, atherosclerosis-susceptible apolipoprotein E–deficient mice leads to abrogation of bone marrow monocytosis and to additive reduction in circulating monocytes despite persistent hypercholesterolemia. These effects are associated with a marked and additive 90% reduction in atherosclerosis. Interestingly, lesion size highly correlates with the number of circulating monocytes, particularly the CD11b + Ly6G − 7/4 lo subset. Conclusions— CCL2, CX3CR1, and CCR5 play independent and additive roles in atherogenesis. Signals mediated through these pathways critically determine the frequency of circulating monocyte subsets and thereby account for almost all macrophage accumulation into atherosclerotic arteries.
GROWTH AND EFFICIENCY OF HOSPITALS
Authors: H. B. HOWARD
Journal: JAMA (1913)

My excuse for taking up any of your time is that I am appointed chairman of this section, and it seems to be one of the duties of the chairman to open the session with a few remarks. I can assure you that nothing that is of interest to general hospitals is foreign to my sympathy. This section was formed, as most of you know, last year, and if its work shall prove to be of benefit to the general hospitals, it will grow and have its excuse for existing. The general hospital is becoming an important factor in most communities, not only of this country, but also of the civilized world. It is almost startling to see what has been accomplished in the multiplication of these hospitals during the last few years. The first hospitals in this country were the New York Hospital, the Pennsylvania Hospital and the Massachusetts
Mitochondrial lesions in reversible erythropoietic depression due to chloramphenicol
Authors: Frank C. Firkin
Journal: Journal of Clinical Investigation (1972)

The mechanism underlying the reversible depression of erythropoiesis by chloramphenicol has been investigated in rabbits in which hemolytic anemia had been induced by phenylhydrazine so that the compensatory erythroid hyperplasia would provide a situation where abnormalities in the bone marrow cells reflected predominantly those of erythroid precursors.
Developments in Child Psychotherapy
Authors: E.J. Anthony
Journal: Psychotherapy and Psychosomatics (1965)

Other Types| February 11 2010 Developments in Child Psychotherapy: Varieties and Vicissitudes of the Therapeutic Situation in the Treatment of Children Subject Area: Psychiatry and Psychology E.J. Anthony E.J. Anthony Washington University School of Medicine, St. Louis, Missouri Search for other works by this author on: This Site PubMed Google Scholar Psychother Psychosom (1965) 13 (1-3): 15–28. https://doi.org/10.1159/000285752 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 E.J. Anthony; Developments in Child Psychotherapy: Varieties and Vicissitudes of the Therapeutic Situation in the Treatment of Children. Psychother Psychosom 31 December 1965; 13 (1-3): 15–28. https://doi.org/10.1159/000285752 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. 1965Copyright / 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.
THERMOMETER IN THE BLADDER
Authors: M. L. Levy
Journal: JAMA (1928)

M. S., a white girl, aged 14, was brought by ambulance to Beth Moses Hospital, Sept. 21, 1927, to be immediately operated on for general peritonitis following acute appendicitis. An emergency operation was performed a few hours later. The patient was very ill, and so the history, of necessity, had to be curtailed to only the pertinent facts. Two days prior to the date of admission, the patient was seized with severe generalized abdominal pains, more so in the uppermost portions of the abdomen. She vomited several times ou the day of onset, and the following day. She felt feverish. The pains subsided for a time but then recurred, on the second day with increased severity, localizing themselves to the right lower quadrant. No urinary symptoms were complained of. She had never menstruated. Physical examination revealed tenderness throughout the entire abdomen, especially in the lower abdomen. There was definite rigidity
NSAIDs prevent, but do not reverse, neuronal cell cycle reentry in a mouse model of Alzheimer disease
Authors: Nicholas H. Varvel, Kiran Bhaskar, Maria Z. Kounnas, Steven L. Wagner, Yan Yang, Bruce T. Lamb, Karl Herrup
Journal: Journal of Clinical Investigation (2009)

Ectopic cell cycle events (CCEs) mark vulnerable neuronal populations in human Alzheimer disease (AD) and are observed early in disease progression. In transgenic mouse models of AD, CCEs are found before the onset of beta-amyloid peptide (Abeta) deposition to form senile plaques, a hallmark of AD. Here, we have demonstrated that alterations in brain microglia occur coincidently with the appearance of CCEs in the R1.40 transgenic mouse model of AD. Furthermore, promotion of inflammation with LPS at young ages in R1.40 mice induced the early appearance of neuronal CCEs, whereas treatment with 2 different nonsteroidal antiinflammatory drugs (NSAIDs) blocked neuronal CCEs and alterations in brain microglia without altering amyloid precursor protein (APP) processing and steady-state Abeta levels. In addition, NSAID treatment of older R1.40 animals prevented new neuronal CCEs, although it failed to reverse existing ones. Retrospective human epidemiological studies have identified long-term use of NSAIDs as protective against AD. Prospective clinical trials, however, have failed to demonstrate a similar benefit. Our use of CCEs as an outcome measure offers fresh insight into this discrepancy and provides important information for future clinical trials, as it suggests that NSAID use in human AD may need to be initiated as early as possible to prevent disease progression.
The age and genomic integrity of neurons after cortical stroke in humans
Authors: Hagen B Huttner, Olaf Bergmann, Mehran Salehpour, Attila Rácz, Jemal Tatarishvili, Emma Lindgren, Tamás Csonka, László Csiba, Tibor Hortobágyi, Gábor Méhes, Elisabet Englund, Beata Werne Solnestam, Sofia Zdunek, Christian Scharenberg, Lena Ström, Patrik Ståhl, Benjamin Sigurgeirsson, Andreas Dahl, Stefan Schwab, Göran Possnert, Samuel Bernard, Zaal Kokaia, Olle Lindvall, Joakim Lundeberg, Jonas Frisén
Journal: Nature Neuroscience (2014)
Intensive therapy and autotransplant for patients with an incomplete response to front-line therapy for lymphoma
Authors: H.M. Prince, M. Crump, K. Imrie, A.K. Stewart, C. Girouard, J.M. Brandwein, K. Carstairs, D. Pantalony, G. Scott, S. Sutcliffe, D.M.C. Sutton, R. Tsang, A. Keating
Journal: Annals of Oncology (1996)
Impact of HR-1 on the Therapy of End-Stage Uremia
Authors: Eli A. Friedman, Samuel L. Kountz
Journal: New England Journal of Medicine (1973)

ON July 1, 1973, Section 299-I of the Social Security Amendments of 1972, termed HR-1, will provide for the payment of maintenance hemodialysis and kidney transplantation for over 90 per cent of the population. Assuming that in 50 new patients per million population treatable irreversible uremia will develop each year (an estimate that excludes other potentially treatable patients with renal failure and multiple system diseases, such as diabetes mellitus), HR-1 will subsidize therapy for at least 50,000 patients within a decade. Supervising the distribution of at least two hundred million and, conceivably, 1/2 billion health-care dollars annually for one specific . . .
PREPARATION AND CHARACTERIZATION OF AN IMMUNOELECTRON MICROSCOPE TRACER CONSISTING OF A HEME-OCTAPEPTIDE COUPLED TO Fab
Authors: J. P. Kraehenbuhl, R. E. Galardy, J. D. Jamieson
Journal: The Journal of Experimental Medicine (1974)

A heme-octapeptide (mol wt 1,550) has been obtained from cytochrome c by successive pepsin and trypsin hydrolysis and purified by gel filtration and countercurrent distribution. It possesses peroxidatic activity characterized by an apparent K(m) of 0.2 M, an apparent v(max) of 4 mmol/min per mg of peptide, and a pH optimum of 7.0. Using a novel two-step conjugation procedure, the heme-octapeptide was coupled to rabbit Fab antibody fragments by first derivatizing it with the N-hydroxysuccinimide ester of p-formylbenzoic acid and subsequently allowing it to form a Schiff base with the amino groups of Fab. Stable covalent linkages were then obtained by reduction of the Schiff bases with sodium borohydride. The conjugate consists of approximately 2 heme-octapeptides attached to each Fab molecule. The molecular weight is 45,000 daltons when coupled to sheep Fab and 50,000 daltons with a Stokes radius of 32 A, when conjugated to rabbit Fab. Its peroxidatic activity is characterized by an apparent K(m) of 0.4 M, an apparent v(max) of 0.4 mmol/min and per mg of attached heme-octapeptide and a pH optimum of 7.0. The conjugate has been used for the localization at the electron microscope level of secretory immunoglobulins in the mammary gland of lactating rabbits.
Abstract A14: Lack of tumor eradication of chemotherapy-sensitive BRCA1;p53-deficient mouse mammary tumors
Authors: Sven Rottenberg, Marina Pajic, Ariena Kersbergen, Nikola Banishki, Guotai Xu, Jos Jonkers, Piet Borst
Journal: Clinical Cancer Research (2010)

Abstract Many breast cancers respond to chemotherapy or hormonal therapy, however, the lack of tumor eradication is a central clinical problem preceding the development of drug resistant tumors. We have previously studied responses of mammary tumors generated in the K14cre;Brca1F5-13/F5-13;p53F2-10/F2-10 mouse model for hereditary breast cancer to clinically relevant anti-cancer drugs such as doxorubicin, topotecan, cisplatin and the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (1-4). The BRCA1- and p53-deficient tumors generated in this model are hypersensitive to these drugs and never become resistant to cisplatin due to the large, irreversible deletion in Brca1 (5). We show here that even dose-dense treatment with a maximum tolerable dose of cisplatin does not result in tumor eradication. This is not due to the trivial possibility that the drug-resistant remnants are poorly accessible to drug, since we found a homogeneous distribution of the platinum-DNA adducts throughout the tumor. To explain this result we have addressed the hypothesis that the lack of eradication of drug-sensitive tumors is due to increased in vivo chemotherapy resistance of tumor-initiating cells (TICs). Using the CD24 and CD49f cell surface markers which detect normal mouse mammary stem cells, we have identified TICs in BRCA1- and p53-deficient tumors. In addition to the Lin-/CD24+/CD49f+ subpopulation, we show that a larger population of Lin-/CD24+/CD49f-cells also has tumor-initiating capability in at least two serial orthotopic transplantations, suggesting that these are not more differentiated transit-amplifying cells. However, we did not find an enrichment of TICs in cisplatin-treated tumor remnants. We conclude that in this model the resistance of cisplatin-surviving cells cannot be attributed to special biochemical defense mechanisms of TICs. Instead we will present data supporting the hypothesis that surviving TICs arrest in their cell cycle and ‘hibernate’ until the drug is gone. Using Brca1−/−;p53−/− cell lines derived from the mouse tumors we found that only Brca1−/−;p53−/− cells that were in the G0/G1 phase of the cell cycle 24h after cisplatin treatment were capable of forming new colonies, whereas cells in G2 or M were not. Hence, a p53-independent arrest in G0/G1 appears to underlie the lack of eradication of residual Brca1−/−;p53−/− cells. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A14
Promising Survival in Patients with Recurrent Non-small Cell Lung Cancer Treated with Docetaxel and Gemcitabine in Combination as Second-Line Therapy
Authors: Chao Hui Huang, Michael M. Millenson, Eric J. Sherman, Hossein Borghaei, David M. Mintzer, Roger B. Cohen, Arthur P. Staddon, Judi Seldomridge, Ocn Joseph Treat, Holly Tuttle, Karen J. Ruth, Corey J. Langer
Journal: Journal of Thoracic Oncology (2008)