tbuckley/cabot-search huggingface dataset:
Abstract B51: Tumor ER stress transmission to infiltrating myeloid cells in vivo require IRE1alpha and TLR4
Authors: Jeffrey J. Rodvold, Nobuhiko Hiramatsu, Kevin T. Chiu, Navin R. Mahadevan, Jonathan Lin, Maurizio Zanetti
Journal: Cancer Research (2013)

Abstract The unfolded protein response (UPR) facilitates tumor outgrowth through evoking a variety of cell intrinsic processes that promote cancer survival, angiogenesis, and chemoresistance. The UPR can be transmitted from stressed cancer cells to receiver myeloid cells in vitro through a process termed transmissible endoplasmic reticulum stress (TERS) in which receiver cells undergo a UPR and acquire tumor promoting pro-inflammatory (IL-6, TNF-alpha, IL-23) and immune-suppressive (Arg1) characteristics. Here, we confirmed that CD11b+ myeloid cells isolated from subcutaneous murine melanoma tumors in C57BL/6 mice display the TERS signature. In light of the fact that TERS signaling in myeloid receiver cells is partly TLR4-dependent, we interrogated subcutaneous tumors in TLR4 mice. We found that these tumors had delayed onset, reduced growth kinetics, and improved survival over tumors growing in wildtype mice. Most significantly, isolated CD11b+ cells from TLR4-/- tumors did not undergo a UPR nor upregulate inflammatory genes when compared to splenic controls, though, interestingly, still upregulated Arg1. Next, we probed individual signaling arms of the UPR in relation to TERS production. We utilized a panel of novel transgenic cell lines in which specific arms of the UPR can be conditionally activated and found that activated inositol requiring enzyme-1alpha (IRE1alpha) transmitted stress to myeloid cells. The remaining two UPR arms (PERK and ATF6) had little transmitting potential, if any. Bone marrow derived myeloid cells treated with TERS generated from IRE1alpha KO mouse embryonic fibroblasts (MEFs) had a markedly reduced UPR than those treated to wildtype MEF TERS. Subcutaneous tumors consisting of IRE1alpha KO TERS-conditioned myeloid dendritic cells and melanoma cancer cells had delayed onset and grew at reduced rate compared to tumor mixtures in which wildtype MEF TERS was used. Based on these data, we probed a patient melanoma for its co-localization of stress, myeloid infiltrate, and inflammation. Together, these data identify a novel signaling mechanism dependent on IRE1alpha and TLR4 used by stressed tumor cells to co-opt infiltrating myeloid cells to become tumor promoting. Citation Format: Jeffrey J. Rodvold, Nobuhiko Hiramatsu, Kevin T. Chiu, Navin R. Mahadevan, Jonathan Lin, Maurizio Zanetti. Tumor ER stress transmission to infiltrating myeloid cells in vivo require IRE1alpha and TLR4. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B51.
The role of GP130 in the liver - differentiation between hepatocytes and non-parenchymal liver cells in CCL4 induced liver injury
Authors: K.L. Streetz, T. Wuestefeld, H. Kreipe, F. Tronche, G. Schuetz, U. Betz, W. Mueller, M. Manns, C. Trautwein
Journal: Journal of Hepatology (2001)
Esophageal Dynamics in Hypergastrinemic Pernicious Anemia Patients.
Authors: Joseph B. Hollis
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Esophageal Dynamics in Hypergastrinemic Pernicious Anemia Patients.Joseph B. Hollis, Raymond L. Farrell, M.D., Donald O. Castell, M.D., F.A.C.P.Joseph B. HollisSearch for more papers by this author, Raymond L. Farrell, M.D.Search for more papers by this author, Donald O. Castell, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-817_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGastrin has been shown to have a specific stimulatory effect on lower esophageal sphincter pressure, and this hormone is believed to be the main determinant of resting sphincter pressure. Recently, the predictable elevated sphincter pressures in hypergastrinemic patients with Zollinger-Ellison syndrome have been shown. Therefore, esophageal function in pernicious anemia patients with elevated serum gastrin levels is of particular interest. We have studied both lower esophageal sphincter and esophageal peristalsis in a group of pernicious anemia patients and age-matched controls. With an infused open-tipped system, mean sphincter resting pressure was 14.8 ± 0.9 (± SE) mm Hg for controls and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Joseph B. Hollis; Raymond L. Farrell, M.D.; Donald O. Castell, M.D., F.A.C.P.Affiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 817-817KeywordsGastrinHormonesPernicious anemiaZollinger Ellison syndrome ePublished: 1 December 2008 Issue Published: 1 May 1973 PDF downloadLoading ...
Management training for clinicians.
Authors: H Waters
Journal: BMJ (1985)

Previous reorganisations of the National Health Service have barely affected the practice and behaviour of doctors. The Griffiths management reforms will, however, draw them much more into the management framework. This management reform is not just about a few doctors becoming general managers, but about all doctors becoming managerially accountable for the quality of their service and the resources that they commit. Historically, the NHS has encompassed two parallel cultures ?the professional and the administrative, with doctors operating from the professional side and committing most of the service's resources. As professionals they see their function as providing the best possible service to individual patients?they are interested in the quality of results?and they set the standards. The adminis? tration sets up the structure and systems to get things done by laying down rules, regulations, and orders aimed primarily at obtaining and deploying as efficiently as possible the resources committed by professionals. When resources were more adequate?or more so than is now the case?the professionals were able to operate according to their value system without conflict with the administration, which in turn maintained the NHS in a steady state. Now, however, the two groups are in conflict because of the need to manage resources. Thus while for most of its existence the NHS has been admini? stered rather than managed the Griffiths inquiry recognised the need for management. Management will care about and under? stand the values of both the professional and administrative sides?it will speak both languages, and get them to work together to provide a service of good quality within the constraints of resources provided by the government.
Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study
Authors: David A. Jacobsohn, Andrew L. Gilman, Alfred Rademaker, Brittan Browning, Michael Grimley, Leslie Lehmann, Eneida R. Nemecek, Kimberly Thormann, Kirk R. Schultz, Georgia B. Vogelsang
Journal: Blood (2009)
Indirubins Decrease Glioma Invasion by Blocking Migratory Phenotypes in Both the Tumor and Stromal Endothelial Cell Compartments
Authors: Shanté P. Williams, Michal O. Nowicki, Fang Liu, Rachael Press, Jakub Godlewski, Mahmoud Abdel-Rasoul, Balveen Kaur, Soledad A. Fernandez, E. Antonio Chiocca, Sean E. Lawler
Journal: Cancer Research (2011)

Invasion and proliferation in neoplasia require the cooperation of tumor cell and endothelial compartments. Glycogen synthase kinase-3 (GSK-3) is increasingly recognized as a major contributor to signaling pathways that modulate invasion and proliferation. Here we show that GSK-3 inhibitors of the indirubin family reduce invasion of glioma cells and glioma-initiating cell-enriched neurospheres both in vitro and in vivo, and we show that β-catenin signaling plays an important role in mediating these effects. Indirubins improved survival in glioma-bearing mice in which a substantial decrease in blood vessel density was seen in treated animals. In addition, indirubins blocked migration of endothelial cells, suggesting that anti-invasive glioma therapy with GSK-3 inhibitors in vivo not only inhibits invasion of tumor cells, but blocks migration of endothelial cells, which is also required for tumor angiogenesis. Overall, our findings suggest that indirubin inhibition of GSK-3 offers a novel treatment paradigm to target 2 of the most important interacting cellular compartments in heterotypic models of cancer.
An Approach to Cerebral Vasodilatory Capacity in Unilateral and Bilateral Cerebrovascular Diseases Using Radiolabeled Human Serum Albumin
Authors: YUSUKE INDUE, TOSHIMITSU MOMOSE, KIKUO MACHIDA, NORINARI HONDA, TOSHIO MAMIYA, TAKU TAKAHASHI, KAZUO TSUTSUMI
Journal: Clinical Nuclear Medicine (1995)

The acute cerebrovascular response to acetazolamide was assessed using a blood pool agent and planar dynamic imaging to evaluate cerebral vasodilatory capacity. Ten normal subjects and 12 patients with unilateral or bilateral cerebrovascular disease were studied. After the injection of radiolabeled human serum albumin, dynamic imaging of the anterior view of the head was started. Ten minutes later, 1000 mg of acetazolamide was infused. The dilatation index (the percent increase in activity at the peak response) was obtained for each cerebral hemisphere. The mean dilatation index in normal subjects was 17.1 +/- 3.2% (N = 20). The value was significantly lower in patients with multiple infarcts (7.7 +/- 1.1%, N = 8, P < 0.001), and below the normal range in two involved hemispheres of five patients with unilateral occlusive carotid artery disease and in three hemispheres of three patients with moyamoya disease. It was suggested that this simple method may be useful in assessing cerebral vasodilatory capacity in both unilateral and bilateral diseases.
Smallpox Vaccination and the WHO
Authors: Joan Stephenson
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Inherited Variation in miR-290 Expression Suppresses Breast Cancer Progression by Targeting the Metastasis Susceptibility Gene <i>Arid4b</i>
Authors: Natalie Goldberger, Renard C. Walker, Chang Hee Kim, Scott Winter, Kent W. Hunter
Journal: Cancer Research (2013)

The metastatic cascade is a complex and extremely inefficient process with many potential barriers. Understanding this process is of critical importance because the majority of cancer mortality is associated with metastatic disease. Recently, it has become increasingly clear that microRNAs (miRNA) play important roles in tumorigenesis and metastasis, yet few studies have examined how germline variations may dysregulate miRNAs, in turn affecting metastatic potential. To explore this possibility, the highly metastatic MMTV-PyMT mice were crossed with 25 AKXD (AKR/J × DBA/2J) recombinant inbred strains to produce F1 progeny with varying metastatic indices. When mammary tumors from the F1 progeny were analyzed by miRNA microarray, miR-290 (containing miR-290-3p and miR-290-5p) was identified as a top candidate progression-associated miRNA. The microarray results were validated in vivo when miR-290 upregulation in two independent breast cancer cell lines suppressed both primary tumor and metastatic growth. Computational analysis identified breast cancer progression gene Arid4b as a top target of miR-290-3p, which was confirmed by luciferase reporter assay. Surprisingly, pathway analysis identified estrogen receptor (ER) signaling as the top canonical pathway affected by miR-290 upregulation. Further analysis showed that ER levels were elevated in miR-290-expressing tumors and positively correlated with apoptosis. Taken together, our results suggest miR-290 targets Arid4b while simultaneously enhancing ER signaling and increasing apoptosis, thereby suppressing breast cancer progression. This, to the best of our knowledge, is the first example of inherited differences in miRNA expression playing a role in breast cancer progression.
Differences in negativity bias underlie variations in political ideology
Authors: John R. Hibbing, Kevin B. Smith, John R. Alford
Journal: Behavioral and Brain Sciences (2014)

Abstract Disputes between those holding differing political views are ubiquitous and deep-seated, and they often follow common, recognizable lines. The supporters of tradition and stability, sometimes referred to as conservatives, do battle with the supporters of innovation and reform, sometimes referred to as liberals. Understanding the correlates of those distinct political orientations is probably a prerequisite for managing political disputes, which are a source of social conflict that can lead to frustration and even bloodshed. A rapidly growing body of empirical evidence documents a multitude of ways in which liberals and conservatives differ from each other in purviews of life with little direct connection to politics, from tastes in art to desire for closure and from disgust sensitivity to the tendency to pursue new information, but the central theme of the differences is a matter of debate. In this article, we argue that one organizing element of the many differences between liberals and conservatives is the nature of their physiological and psychological responses to features of the environment that are negative. Compared with liberals, conservatives tend to register greater physiological responses to such stimuli and also to devote more psychological resources to them. Operating from this point of departure, we suggest approaches for refining understanding of the broad relationship between political views and response to the negative. We conclude with a discussion of normative implications, stressing that identifying differences across ideological groups is not tantamount to declaring one ideology superior to another.
Financing Essential HIV Services: A New Economic Agenda
Authors: Anna Vassall, Michelle Remme, Charlotte Watts, Timothy Hallett, Mariana Siapka, Peter Vickerman, Fern Terris-Prestholt, Markus Haacker, Lori Heise, Andy Haines, Rifat Atun, Peter Piot
Journal: PLoS Medicine (2013)

Anna Vassall and colleagues discuss the need for, and challenges facing, innovative and sustainable financing of the HIV response. Please see later in the article for the Editors' Summary.
GROWTH DIFFERENTIATION FACTOR-15 (GDF-15) AND THE RISK OF CARDIOVASCULAR EVENTS IN PATIENTS WITH STABLE ISCHEMIC HEART DISEASE
Authors: Eri Toda Kato, Marc Bonaca, David Morrow, Petr Jarolim, Sarah Sloan, Scott Solomon, Eugene Braunwald, Marc Sabatine
Journal: Journal of the American College of Cardiology (2014)
Cardiovascular Drugs and the Management of Heart Disease
Authors: Ronald P. Karlsberg
Journal: JAMA (1983)

The prolific introduction of new drugs and therapies makes the task of writing a book that is current on the management of heart disease and cardiovascular drugs a most challenging undertaking. The medicine, cardiology, and pharmacology sections of the University of Arizona, Tucson, have undertaken this challenge. The authors include 22 persons affiliated with the University of Arizona and five others. The book is divided into useful sections, including principles of drug therapy, specific drugs, and chapters emphasizing basic topics in cardiovascular disease, including ischemic heart disease, valvular heart disease, hypertension, hyperlipidemia, congestive heart failure, and other topics. Each chapter is introduced by a concise and useful summary, and the subject index is thorough, allowing ready access to information. With the diffuse range of therapies and cardiovascular drugs originating from multiple investigators across the country, one looks forward to reading these concise reviews. However, the book lacks breadth in comparison
FEEDING EXPERIMENTS WITH BACTERIUM PULLORUM. THE TOXICITY OF INFECTED EGGS
Authors: Leo F. Rettger, Thomas G. Hull, William S. Sturges
Journal: The Journal of Experimental Medicine (1916)

The problem of eradicating ovarian infection in the domestic fowl assumes still greater importance than heretofore, in the light of data recently acquired. Not only is it of great significance to eliminate the permanent carriers of Bacterium pullorum from all flocks of fowls from the standpoint of successful poultry breeding, but also because they constitute a possible source of danger to man. Eggs which harbor Bacterium pullorum in the yolk in large numbers may produce abnormal conditions, when fed, not only in young chicks, but in adult fowls, young rabbits, guinea pigs, and kittens. The toxicity for young rabbits is most pronounced, the infection usually resulting in the death of the animals. In kittens the most prominent symptoms are those of severe food-poisoning with members of the paratyphoid group of bacteria. The possibility of infected eggs causing serious disturbances in young children and in the sick and convalescent of all ages must therefore receive serious consideration. Ovarian infection of fowls is very common throughout this country. Hence, a large proportion of the marketed eggs are infected with Bacterium pullorum. When such eggs are allowed to remain in nests under broody hens, or in warm storage places, for comparatively few hours, they contain large numbers of the organism. Soft boiling, coddling, and frying on one side only do not necessarily render the yolks free from viable bacteria; therefore, eggs which have gone through these processes may, like raw eggs, be the cause of serious disturbances in persons who are particularly susceptible to such influences, and especially to infants. That no well authenticated instances of egg-poisoning of this kind are on record does not warrant the assumption that there have been no cases. The etiology of infantile stomach and intestinal disturbances is as yet too little understood; in fact, it may be said that many of these disorders have no known cause, and almost as much may be said regarding gastro-intestinal diseases in later life. Furthermore, since the ailments caused by infected eggs would not make themselves felt presumably until several days after their ingestion, little or no suspicion would fall upon the eggs. It may be said, too, that the wide distribution of ovarian infection in the domestic fowl has come about only in the last few years, hence its possible danger to man is one of recent development.
A8.21 Rapid downregulation of inflammatory cytokine production in cultured human macrophages after CTLA4-Ig, dexamethasone, and methotrexate combined treatments
Authors: M Cutolo, P Montagna, S Soldano, A Sulli, S Paolino, C Pizzorni, B Seriolo, M Cimmino, R Brizzolara
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> In rheumatoid arthritis (RA) the combination of the fusion protein CTLA4-Ig (abatacept) and other drugs such as glucocorticoids (GC) or/and methotrexate (MTX) allows to obtain better clinical improvement compared to CTLA4-Ig monotherapy. Our recent data showed that CTLA4-Ig, by interacting with the CD86 molecule on RA synovial macrophages, may induce reverse signalling with anti-inflammatory effects, involving NFkB intracellular pathway [1–4]. The anti-inflammatory effect of DEX alone or combined with CTLA4-Ig or/and with CTLA4-Ig plus methotrexate (MTX) was evaluated at gene expression level in cultured human activated macrophages. <h3>Materials and methods</h3> THP-1 cells, activated into macrophages (PMA 0.05 g/ml; 24 h), were cultured for 3 and 24 h with DEX (10<sup>−8</sup> M) alone, DEX combined with CTLA4-Ig (500 g/ml) and DEX with CTLA4-Ig plus MTX (0.05 g/ml). Subsequently, qRT-PCR analysis for IL-1b, TNFa and IL-6 gene expression was performed. Cells untreated were used as controls. <h3>Results</h3> After 3 h, qRT-PCR showed in macrophages treated with DEX alone or with DEX-CTLA4-Ig or DEX-CTLA4-Ig-MTX combined treatment, a significant reduction (p &lt; 0.01) for the expression of all assayed cytokines, compared with controls. CTLA4-Ig alone after 3 hrs, also significant reduced IL-1b (p &lt; 0.01), TNFa (p &lt; 0.05) and IL-6 (p &lt; 0.01) expression. After 24 h, DEX alone or DEX-CTLA4-Ig or DEX-CTLA4-Ig-MTX combined treatments still showed the most significant reduction (p &lt; 0.01) only for IL-1b. After 24 h of DEX-CTLA4-Ig or DEX-CTLA4-Ig-MTX combined treatments TNFa and IL-6 gene expression were still decreased. On the contrary, TNFa and IL-6 gene expression after 24 h of DEX alone treatment resulted unchanged, compared to controls. CTLA4-Ig alone, after 24 h also induced a significant decrease in gene expression for TNFa (p &lt; 0.05) and IL6 (ns), while IL1b expression was unchanged, compared to controls. <h3>Conclusions</h3> DEX and DEX-CTLA4-Ig or DEX-CTLA4-Ig-MTX combined, induced a rapid anti-inflammatory effect on cultured human macrophages, by decreasing proinflammatory cytokine gene expression already after 3 h of treatment. These results seem well correlated with the clinical experience. <h3>References</h3> Cutolo M, Soldano S, Montagna P, <i>et al</i> . <i> Arthritis Res Ther</i> 2009; <b> 11 </b>:176–85. Brizzolara R, Soldano S, Montagna P, <i>et al</i> . Reumatismo 2011; <b> 63 </b>:80–5. Brizzolara R, Montagna P, Soldano S, Cutolo M. <i> J Rheumatol </i> 2013; <b> 40 </b>(5):738–40. Cutolo M, Soldano S, Contini P, <i>et al</i> . <i> Clin Exp Rheumatol </i> 2013; <b> 31 </b>(6):943–6.