tbuckley/cabot-search huggingface dataset:
F(c)gammaRI-targeted fusion proteins result in efficient presentation by human monocytes of antigenic and antagonist T cell epitopes.
Authors: C Liu, J Goldstein, R F Graziano, J He, J K O'Shea, Y Deo, P M Guyre
Journal: Journal of Clinical Investigation (1996)

A major challenge for using native or modified T cell epitopes to induce or suppress immunity relates to poor localization of peptides to antigen presenting cells (APCs) in vivo. In this study, we demonstrate enhanced presentation of antigenic and antagonistic peptides by targeting them to the type I Fc receptor for IgG (F(c)gammaRI, CD64) on human monocytes. A Th epitope of tetanus toxoid, TT830, and the antagonistic peptide for TT830, TT833S, were genetically grafted into the constant region of the heavy chain of the humanized anti-CD64 mAb 22 and expressed as monovalent fusion proteins, Fab22-TT830 and Fab22-TT833S. These CD64-targeted peptides were up to 1,000- and 100-fold more efficient than the parent peptides for T cell stimulation and antagonism, respectively, suggesting that such fusion proteins could effectively increase the delivery of peptides to APCs in vivo. Moreover, the F(c)gammaRI-targeted antagonistic peptide inhibited proliferation of TT830-specific T cells even when APCs were first pulsed with native peptide, a situation comparable with that which would be encountered in vivo when attempting to ameliorate an autoimmune response. These data suggest that targeted presentation of antagonistic peptides could lead to promising Ag-specific therapies for T cell-mediated autoimmune diseases.
Pandemic 2009 Influenza A in Argentina
Authors: Elisa Estenssoro, Fernando G. Ríos, Carlos Apezteguía, Rosa Reina, Jorge Neira, Daniel H. Ceraso, Cristina Orlandi, Ricardo Valentini, Norberto Tiribelli, Matías Brizuela, Carina Balasini, Sebastián Mare, Gustavo Domeniconi, Santiago Ilutovich, Alejandro Gómez, Javiera Giuliani, Cecilia Barrios, Pascual Valdez
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The rapid spread of the 2009 Influenza A (H1N1) around the world underscores the need for a better knowledge of epidemiology, clinical features, outcomes, and mortality predictors, especially in the most severe presentations.To describe these characteristics in patients with confirmed, probable, and suspected viral pneumonia caused by 2009 influenza A (H1N1) admitted to 35 intensive care units with acute respiratory failure requiring mechanical ventilation in Argentina, between June 3 and September 7.Inception-cohort study including 337 consecutive adult patients. Data were collected in a form posted on the Argentinian Society of Intensive Care website.Proportions of confirmed, probable, or suspected cases were 39%, 8%, and 53% and had similar outcomes. APACHE II was 18 +/- 7; age 47 +/- 17 years; 56% were male; and 64% had underlying conditions, with obesity (24%), chronic obstructive respiratory disease (18%), and immunosupression (15%) being the most common. Seven percent were pregnant. On admission, patients had severe hypoxemia (Pa(O(2))/Fi(O(2)) 140 [87-200]), extensive lung radiologic infiltrates (2.87 +/- 1.03 quadrants) and bacterial coinfection, (25%; mostly with Streptococcus pneumoniae). Use of adjuvants such as recruitment maneuvers (40%) and prone positioning (13%), and shock (72%) and acute kidney injury requiring hemodialysis (17%), were frequent. Mortality was 46%, and was similar across all ages. APACHE II, lowest Pa(O(2))/Fi(O(2)), shock, hemodialysis, prone positioning, and S. pneumoniae coinfection independently predicted death.Patients with 2009 influenza A (H1N1) requiring mechanical ventilation were mostly middle-aged adults, often with comorbidities, and frequently developed severe acute respiratory distress syndrome and multiorgan failure requiring advanced organ support. Case fatality rate was accordingly high.
The Need for Reinvention
Authors: Thomas H. Lee
Journal: New England Journal of Medicine (2008)

The editors asked several experts to share their perspectives on the crisis in U.S. primary care. Their articles, which address this crisis from six different angles, follow. We also brought the five U.S. contributors together for a roundtable discussion of the problems and potential solutions for training, practice, compensation, and systemic change. A video of the discussion and reader comments can be seen at www.nejm.org.Primary care has been one of the best jobs in medicine, and it can be again. In fact, primary care must recapture its attraction for the next generation's best trainees — or the chaos and inefficiency of U.S. health care will only worsen.The challenges are formidable, for there are so many reasons for young physicians to go into other fields. Many physicians graduate from medical school with staggering debts, and procedure-oriented specialties offer higher potential incomes. The work of primary care is itself overwhelming. Primary care physicians often go home worried that they may have made mistakes, or dispirited . . .
THE ADVANTAGES OF CASTRATION IN THE DEFECTIVE.
Authors: EVERETT FLOOD
Journal: JAMA (1897)

The conclusions presented are drawn from observation of twenty-six cases. None of the operations have been reported unless more than one year has elapsed and nearly all are more than 2 years old while a good number are from 3 to 8 years old. The ages of the boys vary, but are nearly all between 7 and 15 years. It is very easy for the critic to claim narrowness of view in any one advocating such an operation as this and to offer the usual objections of tradition, but it is not so easy for him to offer us any measure giving equal relief. This is not presented as a panacea but simply for what it is worth and it is not a premature chance thought. The first castrations were performed with the idea of preventing masturbation in certain cases where the habit was most constant and the boy had
Pretransplant prediction of prognosis after liver transplantation in primary sclerosing cholangitis using a cox regression model
Authors: James Neuberger, Bridget Gunson, Piyawat Komolmit, Mervyn H. Davies, Erik Christensen
Journal: Hepatology (1999)

Liver transplantation remains the only treatment for patients with end-stage primary sclerosing cholangitis (PSC); however, selection criteria for the procedure and its timing remains uncertain. The aim of this study was to identify pretransplant variables associated with survival after transplantation and to devise a Cox regression model for prediction of post-transplant survival. We studied 118 patients transplanted for PSC at the Queen Elizabeth Hospital, Birmingham, UK, being followed for up to 91/4 years after the procedure. The association between pretransplant data and the post-transplant survival up to 1 year was studied using the logrank test (univariate analyses) and Cox multiple regression analysis. Univariate analyses showed the following variables to be associated with a decreased post-transplant survival: high serum creatinine, high serum bilirubin, biliary tree malignancy, previous upper abdominal surgery, hepatic encephalopathy, ascites, and Crohn's disease, whereas ulcerative colitis was associated with increased post-transplant survival (all P </=.05). The final multiple Cox regression model included the following significant variables: inflammatory bowel disease, ascites, previous upper abdominal surgery, serum creatinine, and biliary tree malignancy (all P <.03). Biliary tree malignancy could be omitted from the Cox model with only slight loss of information. The results were validated using the data of 30 independent PSC patients from another center. These results can improve selection of patients with PSC for liver transplantation. The developed prognostic model for transplantation can be used in parallel with previously published prognostic models for nontransplantation. The obtained prognostic estimates will provide additional information that is useful for optimal timing of liver transplantation in the individual patient.
Deferred consent in emergency intensive care research: what if the patient dies early? Use the data or not?
Authors: T C Jansen, E J O Kompanje, C Druml, D K Menon, C J Wiedermann, J Bakker
Journal: Intensive Care Medicine (2007)

Respect for individual autonomy, expressed in the concept of informed consent, is the basic ethical principle in research with humans. Many ICU patients are unable to give consent as a consequence of mental incapacity, and this can be further complicated in emergency situations, in which treatment needs to be initiated without delay. Various approaches are used as surrogate to subject consent: waiver of consent, consent by an independent physician and deferred consent. Deferred consent involves randomization at the investigator's discretion according to criteria that have been explicit during ethical review of the protocol, followed by the request for patient's (deferred subject consent) or representative's (deferred proxy consent) informed consent in a later phase. Several emergency trials have used deferred consent [1, 2, 3, 4].

During the enrolment process in an ongoing Dutch multi-centre randomized controlled trial using deferred consent the situation arose that no deferred (subject or proxy) consent was obtained from patients who died early after start of the study. Should data of these patients be used or not? In this article we analyse this practical and ethical problem.
The One-Child Family and Violent Criminality: A 31-Year Follow-Up Study of the Northern Finland 1966 Birth Cohort
Authors: Liisa Kemppainen, Jari Jokelainen, Marjo-Riitta Järvelin, Matti Isohanni, Pirkko Räsänen
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Serious defects in social skills acquired during childhood may be associated with aggressive behavior in later life. The authors studied whether being an only child was associated with criminality in adulthood and, secondly, if parental factors increased the putative risk. METHOD: The authors used an unselected, prospectively collected large birth cohort. Data on crimes were linked with being an only child as well as with perinatal risk and maternal and paternal psychological risk factors among male subjects. RESULTS: The risk for violent crimes later in life was elevated among the only children. If perinatal or parental risks were combined with being an only child, the odds ratios for violent offending increased four-fold to eight-fold. A corresponding risk increase between being an only child and nonviolent offending was not detected. CONCLUSIONS: These results support the hypothesis that growing up as an only child is associated with violent criminality among male subjects.
The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989.
Authors: L S Gold, N B Manley, T H Slone, G B Garfinkel, L Rohrbach, B N Ames
Journal: Environmental Health Perspectives (1993)

This paper is the fifth plot of the Carcinogenic Potency Database (CPDB) that first appeared in this journal in 1984 (1-5). We report here results of carcinogenesis bioassays published in the general literature between January 1987 and December 1988, and in technical reports of the National Toxicology Program between July 1987 and December 1989. This supplement includes results of 412 long-term, chronic experiments of 147 test compounds and reports the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,5,6) for a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The five plots of the database are to be used together, as results of individual experiments that were published earlier are not repeated. In all, the five plots include results of 4487 experiments on 1136 chemicals. Several analyses based on the CPDB that were published earlier are described briefly, and updated results based on all five plots are given for the following earlier analyses: the most potent TD50 value by species, reproducibility of bioassay results, positivity rates, and prediction between species.(ABSTRACT TRUNCATED AT 250 WORDS)
When Politicians Talk about Research
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1979)

The text of a lengthy pep talk that Mr. Califano gave last month to the staff of the National Institutes of Health invites wonder as to why our extraordinarily busy Secretary of Health, Education, and Welfare bothered to make the trip. The same might be asked about the Message on Science and Technology that Mr. Carter recently sent to Congress — the first of its kind since Richard Nixon sent a science message to Congress in 1972, and Mr. Nixon said that was the first of its kind ever sent by any president.These bits and pieces of political attention . . .
BENEFIT OF ATORVASTATIN RELOAD ON ENDOTHELIAL PROGENITOR CELLS IN PATIENTS ON CHRONIC STATIN TREATMENT UNDERGOING PCI
Authors: Elisabetta Ricottini, Rosalinda Madonna, Giuseppe Patti, Domenico Grieco, Alice Zoccoli, Barbara Stampachiacchiere, Andrea D'Ambrosio, Giuseppe Tonini, Raffaele De Caterina, Germano Di Sciascio
Journal: Journal of the American College of Cardiology (2013)
Health care reforms still needed in the nation's prisons
Authors: Phil Gunby
Journal: JAMA (1981)

It is bad enough to go to jail, especially to one of the county or local facilities said to have deplorable health care and other conditions. It is worse if you have pressing physical or psychological problems that helped put you there but remain unnoticed or ignored behind the cell door. Indeed, these so-called screening failures frequently are behind news reports of prisoner deaths from unrecognized illness or injury, inmate suicide, or violent actions by disturbed detainees, say Jay K. Harness, MD, and Lawrence J. Guzzardi, MD, who are advisers (along with Jonas Rappeport, MD, of Baltimore) to the American Medical Association's correctional facilities health care improvement program. These also are among the reasons why jail receiving officers need training in health assessment—and why a nationwide effort to achieve this cannot come too soon. At the recent Fourth National Conference on Medical Care and Health Services in Correctional Institutions sponsored
Failure of frusemide to increase production of prostaglandin E2 in human nasal mucosa in vivo.
Authors: J Mullol, I Ramis, J Prat, J Rosello-Catafau, A Xaubet, C Piera, E Gelpi, C Picado
Journal: Thorax (1993)

BACKGROUND: It has been suggested that inhaled frusemide protects subjects with asthma against bronchoconstriction by enhancing the synthesis of prostaglandin E2 (PGE2). To evaluate this hypothesis the effect of frusemide on PGE2 production from nasal mucosa was studied. METHODS: Two main arachidonic acid metabolites produced by epithelial cells, PGE2 and 15-hydroxy 5,8,11,13-eicosatetraenoic acid (15-HETE), were measured by radioimmunoassay in nasal secretions obtained by nasal lavages with saline. Eleven healthy volunteers were randomly assigned to two study days, one week apart, in a double blind crossover study. Nasal instillation with three increasing doses of frusemide (5, 10, and 20 mg) or placebo was carried out at intervals of 15 minutes. Nasal lavages were performed immediately before nasal instillations and 15, 30, and 60 minutes after the last instillation. RESULTS: Baseline concentrations of 15-HETE were at least six times higher than PGE2. No differences between frusemide and placebo were detected either on PGE2 or 15-HETE release. CONCLUSIONS: The findings do not support the hypothesis that the antiasthmatic effect of frusemide may be due to increased synthesis of PGE2 or release in the respiratory mucosa.
A CASE OF CONGENITAL BILATERAL VENTRAL HERNIA
Authors: Carl G. Leo-Wolf
Journal: JAMA (1924)

Recently, I had a chance through the courtesy of Dr. George P. Eddy of this city to examine a case of a condition that seems to be rather rare, judging from the few cases I have been able to find in the literature accessible to me. An Italian boy, aged 1 year and 9 months, had never been seriously ill. He had had coryza at the age of ten months, and presented evidences, such as the square head and Harrison's groove, of rickets. In the recumbent position, he presented a flattened abdomen with only very slight bulging in both flanks (Fig. 1). When he was sitting up or standing, especially when crying, there was considerable bulging of both flanks (Figs. 2 and 3). Examination showed that the external and internal oblique as well as the transversalis were entirely missing on both sides; the rectus abdominis and the latissimus dorsi on
Hormone Therapy and the Brain: A Clinical Perspective on the Role of Estrogen
Authors: Murray Grossman
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes17 October 2000Hormone Therapy and the Brain: A Clinical Perspective on the Role of EstrogenMurray Grossman, MDMurray Grossman, MDUniversity of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Grossman)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-8-200010170-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Henderson VW. 120 pages. New York: Parthenon; 2000. $58.00. ISBN 1850700788. Order phone 800-735-4744.Field of medicine: General internal medicine, geriatric medicine, obstetrics and gynecology, and neurology.Format: Hardcover book.Audience: Clinicians; residents; and students of internal medicine, geriatrics, obstetrics and gynecology, and neurology.Purpose: To teach physicians and trainees about the beneficial effects of estrogen supplementation for neurologic conditions.Content: An introductory chapter covers the basic physiology and pharmacology of estrogen. Two subsequent chapters summarize the studies indicating the efficacy of estrogen in reducing postmenopausal depression and memory difficulties in otherwise healthy women, two important clinical targets of estrogen ... Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Grossman) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEndogenous sex hormones and cognitive function in older women 17 October 2000Volume 133, Issue 8Page: 660KeywordsAlzheimer diseaseBrainDementiaEstrogensGeriatricsMemoryNeurologyObstetrics and gynecologyStrokeVascular dementia ePublished: 17 October 2000 Issue Published: 17 October 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 912: Targeting HER family signaling in low HER2-expressing breast cancer: activity of the selective and equipotent EGFR, HER2 and HER3 signaling inhibitor, AZD8931, in models of low HER2-expressing disease.
Authors: Gayle Marshall, Susan Ashton, Georgina Speake, Celina D'Cruz, Michael Grondine, Cath Trigwell, Graham Bigley, Garry Beran, Katy Lynaugh, Teresa C. Klinowska
Journal: Cancer Research (2013)

Abstract Effective therapies for women with low-HER2 expressing breast cancer remain a significant unmet clinical need. We have detected significant phosphorylated-HER and HER2:HER3 dimer expression in clinical breast cancer samples without HER2 amplification suggesting that HER signaling may play a role in these tumors. It is our hypothesis that ligand-driven signaling is the major route of HER family activation in the absence of HER2 amplification. AZD8931 is an orally bioavailable and highly selective small molecule inhibitor of EGFR, HER2 and HER3 signaling, which shows greatest potency when HER signaling is ligand-driven(1). In a range of low HER2 breast cancer cell lines, AZD8931 inhibited heregulin-driven proliferation (GI50 range 0.05 to 0.38μM) HER2:HER3 signaling, HER3:PI3K interaction and downstream signaling. In vivo, twice-daily oral dosing of AZD8931 showed significant monotherapy anti-tumor efficacy in a xenograft model of low HER2 breast cancer (MDA-MB-175VII) at well-tolerated doses (90% TGI at 12.5 mg/kg/bid). We further evaluated the activity of AZD8931 in combination with paclitaxel, a commonly used standard of care chemotherapy for patients with advanced breast cancer expressing low levels of HER2. Pre-clinically, the combination of AZD8931 with paclitaxel showed at least additive activity in vitro in a range of breast cell lines and additive efficacy in vivo in a BT474 (high HER2) xenograft model at well tolerated doses (AZD8931 12.5 mg/kg/bid TGI 63%; paclitaxel 7.5mg/kg/qw TGI 41%; combination TGI 95%). Combination work in the low HER2 xenograft model is ongoing. These data demonstrate that AZD8931 inhibits ligand-driven HER family receptor activation, receptor dimerization, PI3K interaction and downstream signaling leading to anti-tumor activity in vivo. These data also support the potential clinical utility of AZD8931 for the therapeutic treatment of low HER2 expressing breast cancers in combination with paclitaxel. 1 Hickinson et al. Clin.Cancer Res (2010) 16:1159-69. Citation Format: Gayle Marshall, Susan Ashton, Georgina Speake, Celina D'Cruz, Michael Grondine, Cath Trigwell, Graham Bigley, Garry Beran, Katy Lynaugh, Teresa C. Klinowska. Targeting HER family signaling in low HER2-expressing breast cancer: activity of the selective and equipotent EGFR, HER2 and HER3 signaling inhibitor, AZD8931, in models of low HER2-expressing disease. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 912. doi:10.1158/1538-7445.AM2013-912
The New Curriculum— Four Years or Ten?
Authors: Thomas Findley
Journal: JAMA (1964)

IT IS IMPROBABLE that many administrators of medical schools are complacent about the present status of medical education. The gap between national health needs and the medical profession's ability to meet them is already wide, and likely to become much more so unless radical changes in pedagogical techniques are made. Defects in the present system have long been recognized, and many remedies have been proposed. One of the most perplexing problems arises when an attempt is made to shorten the curriculum in the face of a staggering growth of scientific knowledge. This is a dilemma which can be solved, under present arrangements, chiefly by requiring more effort from the already overworked student; yet, a number of curricular changes have been advanced. To the extent that the various reforms have a common purpose, their intent seems to be that of providing tomorrow's physicians with a broader training in human biology and
118 Alginate-encapsulated HEPG2 cells in a pilot-scale fluidised bed bioreactor maintain performance in human liver failure plasma making them suitable for use in a bioartificial liver
Authors: S.M. Coward, C. Legallais, M. Thomas, F. Tofteng, F. Larsen, H.J. Hodgson, C. Selden
Journal: Journal of Hepatology (2006)
Hemodynamic and pharmacokinetic study of tertatolol in patients with alcoholic cirrhosis and portal hypertension
Authors: Paul Calès, Hélène Caillau, Olivier Crambes, Jean-Pierre Vinel, Hervé Desmorat, Isabelle Rocher, Louis Jung, Saïk Urien, Rémy Brouard, Jean-Pierre Pascal
Journal: Journal of Hepatology (1993)
Is myocyte dysfunction in end‐stage heart failure reversible by unloading the heart with a left ventricular assist device?
Authors: N. de Jonge, D.F. van Wichen, M.E.I. Schipper, J.R. Lahpor, F.H.J. Gmelig‐Meyling, R.A. de Weger
Journal: European Journal of Heart Failure (2000)