tbuckley/cabot-search huggingface dataset:
Abstract 414: Does hedgehog signaling activation affect the tumor immune suppression microenvironment
Authors: Ling Yang, Dongsheng Gu, Hailan Liu, Xiaoli Zhang, Jingwu Xie
Journal: Cancer Research (2011)

Abstract As an important pathway in embryonic development, hedgehog signaling plays a major role in stem cell maintenance, cell differentiation, tissue differentiation and tissue remodeling. Amounting evidence indicate that hedgehog signaling is frequently activated in a variety of human cancer. In consistent with the stromal effect of hedgehog signaling in development, several recent studies indicate a role of hedgehog signaling in tumor-stromal interaction. The molecular mechanisms by which hedgehog signaling regulates tumor microenvironment, however, remain largely elusive. We have generated data to support that hedgehog signaling regulates tumor immune surveillance. In a mouse model of hedgehog-mediated carcinogenesis, we found that activation of hedgehog signaling is associated with an increase in myeloid-derived suppressor cell (MDSC) population, which is decreased after hedgehog signaling inhibition. Our Based on our data, it is proposed that hedgehog signaling creates an immune suppressive environment through regulation of MDSC population, which is in concert with hedgehog signaling- mediated cell proliferation to promote carcinogenesis. 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 414. doi:10.1158/1538-7445.AM2011-414
Progress in Peptic Ulcer
Authors: Robert A. Levine
Journal: JAMA (1977)

This book summarizes the proceedings of the 1976 meeting of the Third Conference on Experimental Ulcer. The topic is timely, since many advances are being made in research of peptic ulcer. The volume, published entirely in English, is a compendium of 51 papers presented at the conference. The editors have achieved their objective of presenting an up-to-date review on the investigation of peptic ulcer disease. Among the 774 pages of text and data, there are 124 pages of pertinent bibliography. References for each chapter are listed, and to me the bibliography seemed complete. Illustrations are plentiful and clear throughout the book. The text is, in general, also clear and well organized. Some of the illustrations are borrowed from prominent, contemporary sources, while others are original data.  The book has four main divisions. The first is an excellent presentation of the physiological, biochemical, and pharmacologic mechanisms of acid production. The second
Heat Shock Protein 27 Increases after Androgen Ablation and Plays a Cytoprotective Role in Hormone-Refractory Prostate Cancer
Authors: Palma Rocchi, Alan So, Satoko Kojima, Maxim Signaevsky, Eliana Beraldi, Ladan Fazli, Antonio Hurtado-coll, Kazuki Yamanaka, Martin Gleave
Journal: Cancer Research (2004)

Abstract Heat shock protein 27 (Hsp27) is a chaperone implicated as an independent predictor of clinical outcome in prostate cancer. Our aim was to characterize changes in Hsp27 after androgen withdrawal and during androgen-independent progression in prostate xenografts and human prostate cancer to assess the functional significance of these changes using antisense inhibition of Hsp27. A tissue microarray was used to measure changes in Hsp27 protein expression in 232 specimens from hormone naive and posthormone-treated cancers. Hsp27 expression was low or absent in untreated human prostate cancers but increased beginning 4 weeks after androgen-ablation to become uniformly highly expressed in androgen-independent tumors. Androgen-independent human prostate cancer PC-3 cells express higher levels of Hsp27 mRNA in vitro and in vivo, compared with androgen-sensitive LNCaP cells. Phosphorothioate Hsp27 antisense oligonucleotides (ASOs) and small interference RNA potently inhibit Hsp27 expression, with increased caspase-3 cleavage and PC3 cell apoptosis and 87% decreased PC3 cell growth. Hsp27 ASO and small interference RNA also enhanced paclitaxel chemosensitivity in vitro, whereas in vivo, systemic administration of Hsp27 ASO in athymic mice decreased PC-3 tumor progression and also significantly enhanced paclitaxel chemosensitivity. These findings suggest that increased levels of Hsp27 after androgen withdrawal provide a cytoprotective role during development of androgen independence and that ASO-induced silencing can enhance apoptosis and delay tumor progression.
Psychiatry as Part of a Mixed Internship
Authors: Marc H. Hollender
Journal: JAMA (1961)

IN JULY, 1960, a mixed internship in psychiatry and medicine (or pediatrics) was introduced at the Upstate Medical Center of the State University of New York. Since this program is novel and offers certain unique advantages, it would seem appropriate to describe it and to state the reasons for introducing it. The intern spends 6 months each on psychiatry and on medicine (or pediatrics). During the period on psychiatry, he functions much as a junior resident does, in that he is responsible for evaluating and treating hospitalized patients. He receives individual supervision and participates in conferences. Selected seminars are open to him. The opportunity to be involved in an on-going research project is also available. A circumscribed investigation of his own design may be initiated or carried to completion. This is done under a preceptorial arrangement. Every effort is made to stimulate interest in research at this early stage
Systemic circulatory adjustments to acute hypoxia and reoxygenation in unanesthetized sheep. Role of renin, angiotensin II, and catecholamine interactions.
Authors: D Davidson, S A Stalcup
Journal: Journal of Clinical Investigation (1984)

The hemodynamic consequences of the hypoxic inhibition of angiotensin-converting enzyme activity were studied in chronically instrumented unanesthetized sheep (n = 8) breathing a hypoxic gas mixture for 60 min (PaO2 = 31 mm Hg) followed by reoxygenation with room air. Changes in cardiac output, vascular pressures, blood flow distribution, arterial pH, PaCO2, PaO2, and arterial levels of plasma renin activity, angiotensin II, bradykinin, and catecholamines were measured at selected time points. Seven additional sheep underwent the same protocol but received saralasin, an angiotensin II receptor blocker beginning at 55 min of hypoxia and extending into the reoxygenation period. During hypoxia, both groups developed identical hemodynamic patterns including a rise in cardiac output (25%), blood pressure (15%), and preferential blood flow distribution to the heart, brain, adrenals, diaphragm, and skeletal muscle, as well as a decrease in the fraction of cardiac output to the kidneys and most of the gut. This was associated with a decrease in angiotensin II concentrations (from 35 to 17 pg/ml) in spite of a doubling in plasma renin activity and catecholamines. Bradykinin levels did not change. Upon reoxygenation, bolus production of angiotensin II (from 17 to 1,819 pg/ml) occurred in spite of a constant level of plasma renin activity. Concurrently, different hemodynamic patterns between control and saralasin groups emerged upon reoxygenation, including an elevation from base line in blood pressure and systemic vascular resistance in the control group. Cardiac work (heart-rate systolic pressure product) in the control group remained elevated upon reoxygenation while coronary blood flow returned to base-line values. Saralasin reduced cardiac work upon reoxygenation and restored the match between coronary blood flow and work. We conclude that plasma renin activity and oxygen tension together govern angiotensin II levels for an optimal level of systemic vasomotor tone during hypoxia. However, upon reoxygenation, bolus production of angiotensin II may result in pathophysiologic circulatory patterns, such as impairment in oxygen delivery to the myocardium proportional to persistently elevated cardiac work in the immediate postresuscitation period.
Effectiveness of Inactivated Influenza Vaccine in Preventing Acute Otitis Media in Young Children
Authors: Alejandro Hoberman, David P. Greenberg, Jack L. Paradise, Howard E. Rockette, Judith R. Lave, Diana H. Kearney, D. Kathleen Colborn, Marcia Kurs-Lasky, Mary Ann Haralam, Carol J. Byers, Lisa M. Zoffel, Irene A. Fabian, Beverly S. Bernard, Jill D. Kerr
Journal: JAMA (2003)

IRUSES THAT CAUSE RESPIRAtory tract infections are often present in the middle ear exudate of children with acute otitis media (AOM). 1 These viruses may play an important role in the pathogenesis of AOM and may slow the response to antimicrobial therapy. 2,3Accordingly, it seems reasonable to expect that the administration of vaccines effective against viral infections might also serve to lessen morbidity from AOM.Influenza vaccines (inactivated trivalent administered intramuscularly or intranasally or live attenuated trivalent administered intranasally) have been found effective in preventing AOM in 4 previous studies involving children mainly
High levels of disease related prion protein in the ileum in variant Creutzfeldt-Jakob disease
Authors: S Joiner
Journal: Gut (2005)

Disease related prion protein (PrPSc) is readily detectable in lymphoreticular tissues in variant Creutzfeldt-Jakob disease (vCJD) but not in other forms of human prion disease.1–5 This distinctive pathogenesis together with the unknown population prevalence of asymptomatic vCJD infection1,5,6 has led to significant concerns that secondary transmission of vCJD prions will occur through a wide range of surgical procedures.1,3,7 Risk assessment for intestinal endoscopy, biopsy, and surgery is currently limited by a lack of knowledge about relative PrPSc levels and prion titres within intestinal tissues in vCJD patients. Because of its high content of lymphoid follicles, terminal ileum is regarded as the intestinal tissue having the highest potential for iatrogenic transmission of vCJD prions.8,9 Here we provide the first report of relative PrPSc concentrations in vCJD terminal ileum.

Tissues were obtained at autopsy with consent from relatives from four patients with neuropathologically confirmed vCJD and two …
Glucose promotes survival of rat pancreatic beta cells by activating synthesis of proteins which suppress a constitutive apoptotic program.
Authors: A Hoorens, M Van de Casteele, G Klöppel, D Pipeleers
Journal: Journal of Clinical Investigation (1996)

This study demonstrates that rat islet beta cells constitutively express an apoptotic program which is activated when mRNA or protein synthesis is blocked. Apoptotic beta cells were detectable by electron microscopy after treatment with actinomycin D or cycloheximide. With a fluorescence microscopic assay both agents were found to increase the number of apoptotic beta cells dose- and time-dependently, up to 70% after 1 wk of culture; virtually no apoptotic beta cells occurred in control preparations or in conditions leading to primary necrosis. Thus, survival of beta cells seems dependent on synthesis of proteins which suppress an endogenous suicide program. This mechanism explains earlier observed effects of glucose on survival of cultured beta cells. Glucose is known to dose-dependently increase the percentage of beta cells in active biosynthesis and the percentage that survives during culture. It is now demonstrated that the glucose-induced survival of beta cells cultured for 1 wk results from a dose-dependent reduction in the percentage of beta cells dying in apoptosis (49% at 3 mM glucose, 40% at 6 mM, 9% at 10 mM). Thus, intercellular differences in glucose sensitivity appear responsible for the heterogeneity in beta cell sensitivity to apoptotic conditions. These data indicate that glucose promotes survival of beta cells by activating synthesis of proteins which suppress apoptosis. The present model allows for further investigation of the regulation of apoptosis in beta cells and the identification of agents which induce or prevent beta cell death.
Concurrent PPIs and antibiotics for incident<i>C. difficile</i>infection were associated with increased risk for recurrent infection
Authors: Thomas Fekete
Journal: Annals of Internal Medicine (2010)

ACP Journal Club19 October 2010Concurrent PPIs and antibiotics for incident C. difficile infection were associated with increased risk for recurrent infectionThomas Fekete, MDThomas Fekete, MDTemple University School of Medicine, Philadelphia, Pennsylvania, USA (T.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-8-201010190-02012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLinsky A, Gupta K, Lawler EV, Fonda JR, Hermos JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med. 2010;170:772-8. https://pubmed.ncbi.nlm.nih.gov/20458084Clinical Impact RatingsGIM/FP/GP: Hospitalists: Gastroenterology: Geriatrics: Infectious Disease: References1 Garey KW, Sethi S, Yadav Y, Dupont HL. Meta-analysis to assess risk factors for recurrent Clostridum difficile infection. J Hosp Infect. 2008;70:298-304. [PMID: 18951661] Google Scholar2 Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431-55. [PMID: 20307191] Google Scholar3 Turgeon DK, Novicki TJ, Quick J, et al. Six rapid tests for direct detection of Clostridium difficile and its toxins in fecal samples compared with the fibroblast cytotoxicity assay. J Clin Microbiol. 2003;41:667-70. [PMID: 12574264] Google Scholar Author, Article, and Disclosure InformationAuthors: Thomas Fekete, MDAffiliations: Temple University School of Medicine, Philadelphia, Pennsylvania, USA (T.F.)This article was published at Annals.org on 5 October 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 October 2010Volume 153, Issue 8Page: JC4-12KeywordsAntibioticsClostridium infectionsHazard ratioHeart diseasesOutpatientsProton pump inhibitorsPulmonary diseasesSystemic diseasesToxinsVeteran care ePublished: 19 October 2010 Issue Published: 19 October 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease
Authors: Ibrahim Danad, Valtteri Uusitalo, Tanja Kero, Antti Saraste, Pieter G. Raijmakers, Adriaan A. Lammertsma, Martijn W. Heymans, Sami A. Kajander, Mikko Pietilä, Stefan James, Jens Sörensen, Paul Knaapen, Juhani Knuuti
Journal: Journal of the American College of Cardiology (2014)
Novel Cell Culture Technique for Primary Ductal Carcinoma In Situ: Role of Notch and Epidermal Growth Factor Receptor Signaling Pathways
Authors: G. Farnie, R. B. Clarke, K. Spence, N. Pinnock, K. Brennan, N. G. Anderson, N. J. Bundred
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundThe epidermal growth factor receptor (EGFR) and Notch signaling pathways have been implicated in self-renewal of normal breast stem cells. We investigated the involvement of these signaling pathways in ductal carcinoma in situ (DCIS) of the breast.
On the nature of peptides involved in T cell alloreactivity.
Authors: O Rötzschke, K Falk, S Faath, H G Rammensee
Journal: The Journal of Experimental Medicine (1991)

The strong reaction of T cells against foreign major histocompatibility complex (MHC) antigens, commonly termed "alloreactivity", is not only a nuisance for clinical organ transplantation; it also remains a puzzling question for immunologists. By making use of recent technical developments, alloreactive T cells nominally directed against a mutation in a single MHC class I molecule were found to fall into several major categories. One is recognizing peptides whose occurrence is dependent on one particular MHC allele, another is recognizing peptides supported by several MHC alleles, and a third is recognizing peptides occurring independently of MHC alleles. In a fourth category, the binding to MHC of any of a broad range of peptides appears sufficient. In addition, there are T cells for which no peptide involvement could be detected at all. Even within these categories, the heterogeneity of T cells is considerable: among 16 Kb-reactive T cells analyzed, 15 different modes of reactions were found.
Ebola: A holistic approach is required to achieve effective management and control
Authors: Anna Roca, Muhammed O. Afolabi, Yauba Saidu, Beate Kampmann
Journal: Journal of Allergy and Clinical Immunology (2015)

The current Ebola outbreak in West Africa has already caused substantial mortality and dire human and economic consequences. It continues to represent an alarming public health threat in the region and beyond and jeopardizes the provision of health care and other services in the affected countries. The scale of the epidemic has accelerated research efforts for diagnostics, treatment, and prevention galvanized through increased availability of funding. Our knowledge relating to the virus, disease pathogenesis, risk factors, dynamics of transmission, and epidemic control is increasing, and sociocultural factors have emerged as critical determinants for the success and failure of control efforts. However, there is a long way to go. In this review we summarize the current knowledge, examine the sociocultural context in West Africa, and outline priority areas for future research.
Conventional and New Oral Anticoagulants in the Treatment of Chest Disease and Its Complications
Authors: Pilar Gallego, Vanessa Roldan, Gregory Y. H. Lip
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Oral anticoagulants block the coagulation cascade either by an indirect mechanism (e.g., vitamin K antagonists) or by a direct one (e.g., the novel oral anticoagulants). Vitamin K antagonists are widely used as treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. Although low molecular weight heparin remains the first line in venous thromboembolism prophylaxis, more recently the novel oral anticoagulants such as dabigatran (initial dose of 110 mg within 1-4 h after surgery, followed by the full dose of 220 mg once daily), rivaroxaban (dose of 10 mg once daily, with the first dose administered 6-10 h after the surgery), and apixaban (dose of 2.5 mg twice daily, starting 12-24 h after surgery, but available only in Europe) are approved for prophylaxis in patients undergoing major orthopedic surgery. The period in which thromboembolic risk abates remains uncertain, and trials of extended therapy are still ongoing. After showing at least noninferiority to warfarin in RE-LY, ROCKET-AF, and ARISTOTLE trials, dabigatran (110 or 150 mg twice daily), rivaroxaban (20 or 15 mg once daily), and apixaban (5 mg twice daily), respectively, were approved also for stroke prevention in patients with atrial fibrillation. While awaiting long-term safety data, the choice among all these available therapies should be based on patient preferences, compliance, and ease of administration, as well as on local factors affecting cost-effectiveness.
Blinding in Placebo-Controlled Trials
Authors: Norman A. Desbiens
Journal: Annals of Internal Medicine (2001)

Letters19 June 2001Blinding in Placebo-Controlled TrialsNorman A. Desbiens, MDNorman A. Desbiens, MDUniversity of Tennessee College of Medicine—Chattanooga Unit; Chattanooga, TN 37403 (Desbiens)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-12-200106190-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:The motivation for my editorial was not to detract from the work of Dr. Prasad and colleagues (1) but rather to suggest a method that would allow them to use their data on the guess to better understand their findings. Was it the zinc, the suspicion that participants were taking zinc, or both that led to the demonstrated “reduced duration and severity of cold symptoms”? Using regression analysis with duration of cold symptoms as the dependent variable and allocation (placebo/zinc) and the guess (zinc/don't know/placebo) as independent variables would have strengthened the authors' analysis by giving them insight ...Reference1. Prasad AS, Fitzgerald JT, Bao B, Beck FW, Chandrasekar PH. Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;133:245-52. [PMID: 10929163] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Norman A. Desbiens, MDAffiliations: University of Tennessee College of Medicine—Chattanooga Unit; Chattanooga, TN 37403 (Desbiens) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDuration of Symptoms and Plasma Cytokine Levels in Patients with the Common Cold Treated with Zinc Acetate Ananda S. Prasad , James T. Fitzgerald , Bin Bao , Frances W.J. Beck , and Pranatharthi H. Chandrasekar Lessons Learned from Attempts To Establish the Blind in Placebo-Controlled Trials of Zinc for the Common Cold Norman A. Desbiens Blinding in Placebo-Controlled Trials Ananda S. Prasad Blinding in Placebo-Controlled Trials George E. Ehrlich Metrics 19 June 2001Volume 134, Issue 12Page: 1151KeywordsFactor analysisMotivationPsychologyRandomized trialsRegression analysisZinc ePublished: 19 June 2001 Issue Published: 19 June 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Global Farm Animal Production and Global Warming: Impacting and Mitigating Climate Change
Authors: Gowri Koneswaran, Danielle Nierenberg
Journal: Environmental Health Perspectives (2008)

BackgroundThe farm animal sector is the single largest anthropogenic user of land, contributing to many environmental problems, including global warming and climate change.ObjectivesThe aim of this study was to synthesize and expand upon existing data on the contribution of farm animal production to climate change.MethodsWe analyzed the scientific literature on farm animal production and documented greenhouse gas (GHG) emissions, as well as various mitigation strategies.DiscussionsAn analysis of meat, egg, and milk production encompasses not only the direct rearing and slaughtering of animals, but also grain and fertilizer production for animal feed, waste storage and disposal, water use, and energy expenditures on farms and in transporting feed and finished animal products, among other key impacts of the production process as a whole.ConclusionsImmediate and far-reaching changes in current animal agriculture practices and consumption patterns are both critical and timely if GHGs from the farm animal sector are to be mitigated.
New HIV infections down 17% in past eight years
Authors: J. Zarocostas
Journal: BMJ (2009)

The number of new HIV infections globally has been reduced by 17% in the past eight years largely because of more effective prevention policies, say new estimates released this week by UNAIDS and the World Health Organization.

“Most of this progress has been in sub-Saharan Africa where there were 400 000 fewer infections in 2008 than in 2001,” Paul deLay, UNAIDS deputy executive director, told reporters.

In 2008, the agencies estimate there were 33.4 million people living with HIV, 2.7 million were infected with the virus, and 2 million people died of AIDS related illnesses, he said.

“This is clear evidence …
GW25-e0617 Scutellarin Attenuates Myocardial Ischemia Reperfusion Injury by Inhibiting JAK2/STAT3 Pathway
Authors: Li Lin, Wang Lei, Chen Chen, Du Yue, Cai Donghua, Wang Youlan, Yang Jian, Li Jiaxun, Guo Tao, Yang Weimin
Journal: Journal of the American College of Cardiology (2014)