tbuckley/cabot-search huggingface dataset:
Abstract P5-02-02: Specific gene delivery to Her-2+ breast cancer cells using immunoliposomes
Authors: M Kullberg, R McCarthy, TJ Anchordoquy
Journal: Cancer Research (2013)

Abstract The objective of our research is to develop a liposomal gene delivery system that specifically targets potent therapeutic genes to breast cancers which are positive for the human epidermal growth receptor 2 (Her-2). Current liposomal gene delivery systems predominately utilize cationic lipids, which efficiently bind and deliver plasmid DNA, but also result in nonspecific gene expression in the lungs and liver tissue. We attempt to improve on specificity, by using a two-component delivery system. The first component is a cationic polyethylene glycol (PEG) grafted polylysine which carries the plasmid DNA. The polylysine/DNA particle binds nonspecifically to cells but has limited ability to bypass the endosomal membrane. The second component is an anionic Her-2 targeting liposome which is disulfide bound to the pore forming protein Listeriolysin O (LLO). These liposomes bind with high selectivity to Her-2 positive cells and once internalized into the reducing conditions of an endosome, release LLO which forms pores in the endosomal membrane. Neither component delivers DNA plasmid on its own, but if the polylysine/DNA and LLO/liposome co-localize within an endosome, the DNA is able to access the cytoplasm which leads to gene expression of the plasmid. Using fluorescent microscopy and a cell panel, we show that labeled polylysine/DNA and LLO/liposomes have a much greater chance of co-localizing in an endosome of Her-2 positive breast cancer cells compared to Her-2 negative cells. In addition, utilizing luciferase plasmid, we demonstrate that this two-component system results in gene expression that is over 1000-fold greater in Her-2 overexpressing cells than in Her-2 negative cells. This is a vast improvement over standard cationic liposome techniques which show no specificity for Her-2 positive cells. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-02-02.
Time to act against medical collusion in punitive amputations
Authors: Adebayo Adejumo, Prisca Olabisi Adejumo
Journal: BMJ (2005)

Punitive surgical amputations are a negation of the basic principles and ethics of surgery taught in medical schools. Media reports show a frightening picture. For example, in Iraq a physician who worked in a Baghdad hospital in 1994 estimated that 1700 amputations had been performed on army deserters between August and mid-September 1994 ( Daily Telegraph 1994 Nov 1: 21). This physician reported that procedures were often done without anaesthesia and that the risk of infection was high because of poor hygiene. Another physician in Iraq participated in an ear amputation while the patient was tied to a bed. In northern Nigeria the amputation of the hand of a cow thief, Buba Jangebe, as sharia punishment for cow theft was carried out within the purview of physicians (http://news.bbc.co.uk/2/hi/africa/2587039.stm). On 28 February 1998 four doctors in Kabul performed amputations on two men before a …
Rapid polymerization of Entamoeba histolytica actin induced by interaction with target cells.
Authors: G B Bailey, D B Day, J W Gasque
Journal: The Journal of Experimental Medicine (1985)

Within 5 s of challenge of Entamoeba histolytica trophozoites with red blood cells (RBC), attachment and deformation of target cells occurred at multiple sites on the amoeba surface. Many trophozoite-target interfaces were outlined with a ring of polymerized amoeba actin, revealed by rhodamine-phalloidin staining of glutaraldehyde-fixed and Triton-X 100-extracted cells. The beginnings of phagocytic pseudopods rimmed many targets. The phagocytic membrane and underlying actin network grew uniformly about a target cell, which became dramatically elongated and constricted, sometimes severed, as it entered the amoeba. Total engulfment of RBC targets occurred within 10 s. By methanol extraction and spectrofluorimetric measurement of bound rhodamine-phalloidin we were able to quantitate polymerized actin in amoebae. Interaction with target cells was accompanied by a net increase of up to twofold in the average polymerized actin content of trophozoites. This reached a maximum during the period of most active phagocytosis (4 min after challenge at 25 degrees C), and declined as phagocytic activity diminished (8-16 min). Challenge with latex beads of similar size and number, which E. histolytica phagocytized more slowly than RBC, induced neither a detectable increase in polymerized actin content nor appearance of polymerized actin at the contact interface. RBC inhibited phagocytosis of latex beads, but the reverse did not occur. The results demonstrate a rapid, recognition-specific stimulation of reorganization of the actin cytoskeleton of E. histolytica induced by binding to target cells. Vigorous phagocytic activity is frequently an immediate consequence of cell-cell contact, which emphasizes the importance of this process in the contact-mediated attack mechanism of this pathogen. The quantitative assay of polymerized actin may be useful in further studies of this mechanism.
Hong Kongs public health system turns to private sector for help
Authors: J. Parry
Journal: BMJ (2002)

The chairman of Hong Kong's Hospital Authority, Dr Leong Che-hung, has urged more partnerships between the city's public and private hospitals in a bid to ease the burden on the public sector.

The hospital authority manages 44 of Hong Kong's 56 hospitals and treats 93% of the total number of patients in the region; treatment is 97% subsidised. Encouraging patients to migrate to the private sector would enable public hospitals to reallocate resources to areas where need is greater, Dr Leong said.

“The public sector is basically very good and very cheap but has become a victim of its own success and is overloaded. I'm sure there are a lot of patients who …
Genome-wide association study identifies three new melanoma susceptibility loci
Authors: Jennifer H Barrett, Mark M Iles, Mark Harland, John C Taylor, Joanne F Aitken, Per Arne Andresen, Lars A Akslen, Bruce K Armstrong, Marie-Francoise Avril, Esther Azizi, Bert Bakker, Wilma Bergman, Giovanna Bianchi-Scarrà, Brigitte Bressac-de Paillerets, Donato Calista, Lisa A Cannon-Albright, Eve Corda, Anne E Cust, Tadeusz Dębniak, David Duffy, Alison M Dunning, Douglas F Easton, Eitan Friedman, Pilar Galan, Paola Ghiorzo, Graham G Giles, Johan Hansson, Marko Hocevar, Veronica Höiom, John L Hopper, Christian Ingvar, Bart Janssen, Mark A Jenkins, Göran Jönsson, Richard F Kefford, Giorgio Landi, Maria Teresa Landi, Julie Lang, Jan Lubiński, Rona Mackie, Josep Malvehy, Nicholas G Martin, Anders Molven, Grant W Montgomery, Frans A van Nieuwpoort, Srdjan Novakovic, Håkan Olsson, Lorenza Pastorino, Susana Puig, Joan Anton Puig-Butille, Juliette Randerson-Moor, Helen Snowden, Rainer Tuominen, Patricia Van Belle, Nienke van der Stoep, David C Whiteman, Diana Zelenika, Jiali Han, Shenying Fang, Jeffrey E Lee, Qingyi Wei, G Mark Lathrop, Elizabeth M Gillanders, Kevin M Brown, Alisa M Goldstein, Peter A Kanetsky, Graham J Mann, Stuart MacGregor, David E Elder, Christopher I Amos, Nicholas K Hayward, Nelleke A Gruis, Florence Demenais, Julia A Newton Bishop, D Timothy Bishop
Journal: Nature Genetics (2011)
The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.
Authors: S Qin, J B Rottman, P Myers, N Kassam, M Weinblatt, M Loetscher, A E Koch, B Moser, C R Mackay
Journal: Journal of Clinical Investigation (1998)

T cells infiltrating inflammatory sites are usually of the activated/memory type. The precise mechanism for the positioning of these cells within tissues is unclear. Adhesion molecules certainly play a role; however, the intricate control of cell migration appears to be mediated by numerous chemokines and their receptors. Particularly important chemokines for activated/memory T cells are the CXCR3 ligands IP-10 and Mig and the CCR5 ligands RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta. We raised anti-CXCR3 mAbs and were able to detect high levels of CXCR3 expression on activated T cells. Surprisingly, a proportion of circulating blood T cells, B cells, and natural killer cells also expressed CXCR3. CCR5 showed a similar expression pattern as CXCR3, but was expressed on fewer circulating T cells. Blood T cells expressing CXCR3 (and CCR5) were mostly CD45RO+, and generally expressed high levels of beta1 integrins. This phenotype resembled that of T cells infiltrating inflammatory lesions. Immunostaining of T cells in rheumatoid arthritis synovial fluid confirmed that virtually all such T cells expressed CXCR3 and approximately 80% expressed CCR5, representing high enrichment over levels of CXCR3+ and CCR5+ T cells in blood, 35 and 15%, respectively. Analysis by immunohistochemistry of various inflamed tissues gave comparable findings in that virtually all T cells within the lesions expressed CXCR3, particularly in perivascular regions, whereas far fewer T cells within normal lymph nodes expressed CXCR3 or CCR5. These results demonstrate that the chemokine receptor CXCR3 and CCR5 are markers for T cells associated with certain inflammatory reactions, particularly TH-1 type reactions. Moreover, CXCR3 and CCR5 appear to identify subsets of T cells in blood with a predilection for homing to these sites.
One or two 7.5-µg doses of MF59-adjuvanted influenza A (H1N1) 2009 vaccine was immunogenic in adults within 21 days
Authors: Bruno Granwehr
Journal: Annals of Internal Medicine (2010)

ACP Journal Club19 January 2010One or two 7.5-µg doses of MF59-adjuvanted influenza A (H1N1) 2009 vaccine was immunogenic in adults within 21 daysBruno Granwehr, MD, MSBruno Granwehr, MD, MSUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USA (B.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-2-201001190-02008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationClark TW, Pareek M, Hoschler K, et al. Trial of influenza A (H1N1) 2009 monovalent MF59-adjuvanted vaccine—preliminary report. N Engl J Med. 2009;361. https://pubmed.ncbi.nlm.nih.gov/19745215Clinical Impact RatingsGIM/FP/GP: Infectious Disease: Pulmonology: References1 Chan M. World now at the start of 2009 influenza pandemic. www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html (accessed 24 Nov 2009). Google Scholar2 Rowe T, Abernathy RA, Hu-Primmer J, et al. Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays. J Clin Microbiol. 1999;37:937-43. [PMID: 10074505] Google Scholar3 Romero Méndez IZ, Shi Y, HogenEsch H, Hem SL. Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants. Vaccine. 2007;25:825-33. [PMID: 17014935] Google Scholar4 Atmar RL, Keitel WA, Patel SM, et al. Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2 vaccine preparations. Clin Infect Dis. 2006;43:1135-42. [PMID: 17029131] Google Scholar5 Centers for Disease Control and Prevention (CDC). Surveillance for the 2009 pandemic influenza A (H1N1) virus and seasonal influenza viruses—New Zealand, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:918-21. [PMID: 19713880] Google Scholar6 National Institute of Allergy and Infectious Diseases. Pediatric H1N1 vaccine clinical studies. www3.niaid.nih.gov/topics/Flu/H1N1/Research/children.htm (accessed 24 Nov 2009). Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas MD Anderson Cancer Center, Houston, Texas, USA (B.G.)This article was published at Annals.org on 5 January 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA 15-µg dose of unadjuvanted influenza A (H1N1) 2009 vaccine was immunogenic in healthy adults within 21 days Bruno Granwehr Metrics 19 January 2010Volume 152, Issue 2Page: JC1-8KeywordsAntibody productionChildrenH1N1Respiratory system proceduresSafetySwine influenzaSystemic diseasesTemperatureUpper respiratory tract infectionsVaccines ePublished: 19 January 2010 Issue Published: 19 January 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study
Authors: Claus G. Roehrborn, Paul Siami, Jack Barkin, Ronaldo Damião, Kim Major-Walker, Indrani Nandy, Betsy B. Morrill, R. Paul Gagnier, Francesco Montorsi
Journal: European Urology (2009)
Accepting Risk in Clinical Research: Is the Gene Therapy Field Becoming Too Risk-averse?
Authors: Claire T Deakin, Ian E Alexander, Ian Kerridge
Journal: Molecular Therapy (2009)

Risk is an inescapable aspect of clinical research and is increasingly pertinent to the gene therapy field as the imperative for clinical trial activity grows. In recent years, the widely reported occurrence of serious adverse events (SAEs) in gene therapy studies, including trials for ornithine transcarbamylase (OTC) deficiency, X-linked severe combined immunodeficiency (SCID-X1), and rheumatoid arthritis, has heightened fear in public perceptions of gene therapy. Although it is essential to be cognizant of the risks involved in gene therapy research, there is a danger that gene therapy may become too risk-averse. If the field is to make progress, it is necessary to understand how risk is defined in gene therapy research, how understandings of risk differ, how risk is assessed, how decisions about risk are made, and how gene therapy risks are communicated to subjects and research participants during the informed consent process. In addition to minimizing the risks of clinical research through extensive preclinical safety studies, attention should be given to how decisions about risk and risk acceptability are made by researchers and subjects, and to the methods used to communicate risks to patients. Critical attention to risk will help ensure that the safety of subjects is protected, while also enabling research to develop better treatments for patients.
Shell-Shock: A History of the Changing Attitude to War Neurosis
Authors: R. Earlam
Journal: BMJ (1998)

Anthony Babington Leo Cooper, £16.95, pp 224 ISBN 085052 5624

The failure to compensate psychologically for the trauma of war has been called many things over the years. This important book charts the shifts in attitudes that have accompanied the changing names.

In 1678, a Swiss physician coined the term “nostalgia” to mean a soldier's fear that he would never see …
Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis
Authors: J E Salmon, G Girardi, V M Holers
Journal: Annals of the Rheumatic Diseases (2002)

The antiphospholipid antibody syndrome (APS) is characterised by increased risk of vascular thrombosis involving venous, arterial, and placental circulations. The last of these is associated with poor obstetrical outcomes, including fetal death and growth retardation. Pregnancy loss is a defining criterion for APS and occurs with particularly high frequency in systemic lupus erythematosus (SLE) patients bearing this antibody. Patients meet the criteria for APS if they have three otherwise unexplained embryonic losses (before 10 weeks gestation) or one otherwise unexplained fetal loss after 10 weeks, with or without placental infarction or fetal growth restriction.1–3

Over the past two decades, APS has emerged as a leading cause of pregnancy loss and pregnancy related morbidity. It is now recognised that recurrent miscarriage occurs in 1% of couples,4–7 that up to 20% of women with recurrent miscarriage have antiphospholipid (aPL) antibodies, and that in about 15% of otherwise apparently normal women aPL is the sole explanation for recurrent fetal loss.8,9 The primary treatment for these patients, anticoagulation throughout pregnancy, is inconvenient, sometimes painful, expensive, and fraught with potential complications, including haemorrhage and osteoporosis. Moreover, it is often ineffective. Thus, the identification of a novel mechanism for pregnancy loss in women with aPL antibodies holds the promise of new, safer, and better treatments.

Awareness of the association of aPL antibodies with pregnancy complications has increased the frequency with which APS is diagnosed and generated substantial interest in elucidating its pathophysiology. At present, though the association of aPL antibodies with pregnancy loss and pregnancy morbidity is secure, its mechanism remains unknown.10 Defining this mechanism is crucial for several reasons. Firstly, there is considerable variability in the success rates of the various treatments,11 suggesting that different but still undefined treatments may be optimal in specific subsets of women …
Treatment of AIDS With Transfer Factor
Authors: John T. Carey, Michael M. Lederman
Journal: JAMA (1987)

<h3>To the Editor.—</h3> We have recently described our experience in treating patients with acquired immunodeficiency syndrome (AIDS) with transfer factor (TF) pooled from donors (healthy laboratory workers) and from homosexual men with serum antibodies to the human immunodeficiency virus (HIV) who had had stable lymphadenopathy for a period of more than one year. Administration of pooled TF resulted in the acquisition of skin test responses, improvement in lymphocyte blastogenesis, and increased natural killer cell activity.<sup>1</sup> We now report our preliminary experience using TF prepared from normal donors only. <h3>Study.—</h3> Transfer factor was prepared as previously described<sup>1</sup>from three healthy donors who had positive skin test responses to mumps and one who had positive skin test responses to both mumps and purified protein derivative. After informed consent was obtained, four patients with AIDS received weekly subcutaneous injections of 5 × 10<sup>8</sup>leukocyte equivalents of TF and were evaluated
Increasing handicaps in hospital medicine: two point cross sectional study of golfing activity among doctors
Authors: J. M Eagles, G. B Rhind
Journal: BMJ (1997)

between grade differences for total chocolate scores (F = 8.3, P < 0.01, df = 4).Post hoc analyses (the Newman Keuls procedure) showed that scores for the post-registration house officers were significantly better than scores for the preregistration house officers, registrars, and consultants.In addition, a significant inverse correlation existed between years post registration and total scores for chocolate recognition (Pearson's r = -0.47,P < 0.01).The nurses performed as well as the post-registration house officers.The "coffee creme" chocolate was recognised by most subjects at all grades.
Oligoclonal Bands in Serum Protein Electrophoretograms of Individuals With Human Immunodeficiency Virus Antibodies
Authors: David M. Kouns
Journal: JAMA (1986)

To the Editor.—  Two recent reports have documented the presence of oligoclonal bands in the serum 1 and cerebrospinal fluid 2 of patients with acquired immunodeficiency syndrome (AIDS). These bands were found to be composed of IgG immunoglobulins of unknown specificity. The finding is important from a pathophysiological perspective, but lacks diagnostic significance since all of the patients described manifested AIDS prior to the recognition of the oligoclonal bands. We report the discovery of oligoclonal bands in the serum of seven patients with antibodies to human immunodeficiency virus (HIV) who do not yet manifest AIDS. The presence of oligoclonal bands in the serum should alert the clinician to the possibility of HIV-related disease.  Methods.—  We conducted a retrospective review of over 2500 serum protein electrophoretograms performed over a 16-month period. Approximately 1% (24 electrophoretograms from 19 patients) demonstrated oligoclonal paraprotein bands in the γ-globulin region. The Figure shows a typical
Medicare at 25
Authors: Gail R. Wilensky
Journal: JAMA (1990)

Since implementation of the Medicare Prospective Payment System (PPS) in 1983, public policy debate has centered largely on whether the payment changes have broken the back of health care inflation. The reforms of that year represented the single largest change in payment policy since the inception of the Medicare program. The PPS in large part broke the link between hospital-specific costs and hospital inpatient payments. Moreover, the system created strong financial incentives for hospitals and physicians providing care in their institutions to treat patients more efficiently. The impact of the PPS on hospitals was significant. The average length of stay for Medicare patients in short-stay hospitals decreased from 10.0 days in fiscal year 1983 to 8.5 days for PPS hospitals in fiscal year 1989. The decrease was even more dramatic for the five conditions in the study reported in this issue ofThe Journal: from 14.4 days in fiscal year
Immunochemical similarities between monoclonal antibacterial Waldenstrom's macroglobulins and monoclonal anti-DNA lupus autoantibodies.
Authors: Y Naparstek, D Duggan, A Schattner, M P Madaio, F Goni, B Frangione, B D Stollar, E A Kabat, R S Schwartz
Journal: The Journal of Experimental Medicine (1985)

Six monoclonal IgM from patients with Waldenstrom's macroglobulinemia that react with Klebsiella polysaccharides were tested for their ability to bind to nucleic acid antigens. One of the macroglobulins bound to the polynucleotide poly(G), and one bound to poly(G), poly(I), and single-stranded DNA. The reaction with the polynucleotides was specifically inhibited by the Klebsiella polysaccharide K30. A monoclonal lupus anti-DNA antibody (16/6) was found to react weakly with the Klebsiella polysaccharides K30 and K21. Five of the Waldenstrom macroglobulins shared an idiotypic determinant with the 16/6 anti-DNA antibody. The reaction between the macroglobulins and the antiidiotype serum was specifically inhibited by Klebsiella polysaccharides, an indication that the idiotypic marker was in the antigen-binding site of the macroglobulins. These results indicate the existence of widely dispersed conserved variable region genes that encode idiotypically related immunoglobulins with the capacity to bind to both bacterial polysaccharides and nucleic acids. Such genes can be expressed by patients with either Waldenstrom's macroglobulinemia or systemic lupus erythematosus.