tbuckley/cabot-search huggingface dataset:
Allergy, Asthma, Hay Fever, Urticaria and Allied Manifestations of Reaction.
Journal: JAMA (1925)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
US physician group calls for ban on direct to consumer drug advertising
Authors: M. McCarthy
Journal: BMJ (2015)

The American Medical Association has called for a ban on all direct to consumer advertising of prescription drugs and medical devices. The new policy, adopted on 17 November at the AMA’s interim meeting in Atlanta, Georgia, also called for the federal government to limit anticompetitive behavior by drug companies.

In a statement Patrice A Harris, AMA board chair elect, said that direct to consumer advertising was inflating demand for new and more expensive drugs that may not be appropriate.“Today’s vote in support …
Mutant calreticulin‐expressing cells induce monocyte hyperreactivity through a paracrine mechanism
Authors: Michael R. Garbati, Catherine A. Welgan, Sally H. Landefeld, Laura F. Newell, Anupriya Agarwal, Jennifer B. Dunlap, Tapan K. Chourasia, Hyunjung Lee, Johannes Elferich, Elie Traer, Rogan Rattray, Michael J. Cascio, Richard D. Press, Grover C. Bagby, Jeffrey W. Tyner, Brian J. Druker, Kim‐Hien T. Dao
Journal: American Journal of Hematology (2015)

Mutations in the calreticulin gene ( CALR ) were recently identified in approximately 70–80% of patients with JAK2‐ V617F‐negative essential thrombocytosis and primary myelofibrosis. All frameshift mutations generate a recurring novel C‐terminus. Here we provide evidence that mutant calreticulin does not accumulate efficiently in cells and is abnormally enriched in the nucleus and extracellular space compared to wildtype calreticulin. The main determinant of these findings is the loss of the calcium‐binding and KDEL domains. Expression of type I mutant CALR in Ba/F3 cells confers minimal IL‐3‐independent growth. Interestingly, expression of type I and type II mutant CALR in a nonhematopoietic cell line does not directly activate JAK/STAT signaling compared to wildtype CALR and JAK2‐ V617F expression. These results led us to investigate paracrine mechanisms of JAK/STAT activation. Here we show that conditioned media from cells expressing type I mutant CALR exaggerate cytokine production from normal monocytes with or without treatment with a toll‐like receptor agonist. These effects are not dependent on the novel C‐terminus. These studies offer novel insights into the mechanism of JAK/STAT activation in patients with JAK2‐ V617F‐negative essential thrombocytosis and primary myelofibrosis. Am. J. Hematol. 91:211–219, 2016. © 2015 Wiley Periodicals, Inc.
Red-Brown Plaques and Papules in a Patient With Breast Cancer
Authors: Hsien-Yi Chiu, Hsien-Neng Huang
Journal: JAMA (2015)

A 55-year-old woman presented with a generalized erythematous maculopapular rash after receiving breast cancer chemotherapy. She was afebrile and had no constitutional symptoms; laboratory evaluation revealed pancytopenia, and a computed tomography scan showed no metastasis. What would you do next?
Implementation of the Lancet Standing Commission on Liver Disease in the UK
Authors: Roger Williams, Kathryn Ashton, Richard Aspinall, Mark A Bellis, Joanne Bosanquet, Matthew E Cramp, Natalie Day, Anil Dhawan, John Dillon, Jessica Dyson, James Ferguson, Graham Foster, Sir Ian Gilmore, Michael Glynn, J Ashley Guthrie, Mark Hudson, Deirdre Kelly, Andrew Langford, Philip Newsome, John O'Grady, Rachel Pryke, Stephen Ryder, Marianne Samyn, Nick Sheron, Julia Verne
Journal: The Lancet (2015)
Modulation of Endothelial Hemostatic Properties: An Active Role in the Host Response
Authors: Herwig Gerlach, Ciro Esposito, David M. Stern
Journal: Annual Review of Medicine (1990)

As the cells forming the luminal vascular surface, endothelium regulates both barrier function, and pro- and anticoagulant reactions. Endothelial cells can do this by controlling the expression of cell surface molecules, such as receptors that regulate the hemostatic balance and those that affect permeability across the endothelial monolayer. This regulation occurs in response to environmental stimuli, such as cytokines, which have a central role in inflammation, or glucose-modified proteins, which accumulate in the vasculature in aging and diabetes and are associated with vascular complications. The endothelial cell emerges as a dynamic regulator maintaining homeostasis in the quiescent state and contributing to the pathogenesis of vascular lesions in the stimulated state.
Stable Isotope Methods for Nutritional Investigation
Authors: Dwight E. Matthews, Dennis M. Bier
Journal: Annual Review of Nutrition (1983)

IN TRODUCTI ON . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....... . . . . . . . . . . . . . . 309 INSTRUMENTATION . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311 Isoto pe Ratio Mass S pectromet ry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 4 Techni ques Ancillary to IRMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 14 Gas Chromatogra phy-Mass S pectrometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 5 END PRODUC T METH ODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 7 Natura lly La be led Tracers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 17 Tests of Gastrointestinal Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 7 Protein Turnover . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 KINE TICS OF INDIVIDUAL METAB OLI TES . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . 3 1 9 Carbohydrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 9 Fatty Acids and Cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 Direct Measurement of Protein Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 B ODY WA TER AND ENERGY EXPENDI TURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323 TOTAL B ODY NITR OG EN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 INORGANIC ELEMENTS  325 C ONCLUSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
International cooperation to improve access to and sustain effectiveness of antimicrobials
Authors: Christine Årdal, Kevin Outterson, Steven J Hoffman, Abdul Ghafur, Mike Sharland, Nisha Ranganathan, Richard Smith, Anna Zorzet, Jennifer Cohn, Didier Pittet, Nils Daulaire, Chantal Morel, Zain Rizvi, Manica Balasegaram, Osman A Dar, David L Heymann, Alison H Holmes, Luke S P Moore, Ramanan Laxminarayan, Marc Mendelson, John-Arne Røttingen
Journal: The Lancet (2015)
Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials
Authors: Christophe Le Tourneau, Maud Kamal, Apostolia-Maria Tsimberidou, Philippe Bedard, Gaëlle Pierron, Céline Callens, Etienne Rouleau, Anne Vincent-Salomon, Nicolas Servant, Marie Alt, Roman Rouzier, Xavier Paoletti, Olivier Delattre, Ivan Bièche
Journal: JNCI Journal of the National Cancer Institute (2015)

With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials.
Prognostic importance of cytogenetic subgroups in de novo pediatric acute nonlymphocytic leukemia.
Authors: D K Kalwinsky, S C Raimondi, M J Schell, J Mirro, V M Santana, F Behm, G V Dahl, D Williams
Journal: Journal of Clinical Oncology (1990)

Reports of close associations between recurring chromosomal abnormalities and the clinical behavior of acute nonlymphocytic leukemia (ANLL) have stimulated efforts to define this disease in cytogenetic terms. Here we report on the leukemic cell karyotypes of 155 children with ANLL who were treated from 1980 to 1987 in consecutive programs of chemotherapy at this institution. Of 121 cases with adequate banding, 20% were normal, 30% had miscellaneous clonal abnormalities, and 50% were classified into known cytogenetic subgroups: inv(16)/del(16q) (n = 15), t(8; 21) (n = 14), t(15;17) (n = 9), t(9;11) (n = 9), t(11;V)/del(11q) (n = 7) and -7/del(7q) (n = 6). The inv(16)/del(16q) cases showed a nearly equal distribution of myelocytic and monocytic French-American-British (FAB) subtypes; only four of these patients presented with M4Eo morphology. Despite a 100% remission induction rate, patients with inv(16)/del(16q)-positive ANLL fared no better overall than the entire group; only 40% of this subgroup were event-free survivors at 2 years from diagnosis (P = .23). Patients with inv(16)/del(16q) frequently had CNS involvement at diagnosis (eight of 15) or initially relapsed in this site (three of eight). Event-free survival (EFS) was clearly superior for young patients with FAB M5 leukemia and the t(9;11) (P = .041). These patients were clinically indistinguishable from others with the FAB disease subtype, yet their responses to etoposide-containing therapies were noteworthy. By contrast, children with structural abnormalities involving 11q23, other than t(9;11), were infants (median age, 6 months) with FAB M4 or M5 leukemia, hyperleukocytosis, and frequent coagulation abnormalities. Patients with such changes [t(11;V) or del(11q)] relapsed early during postremission therapy: none remained disease-free more than 16 months from diagnosis. Because of resistant leukemia, patients with monosomy 7/del(7q) had a poor remission induction rate (17%; P = .0015); patients with the t(15;17) were also poor responders to induction therapy (44%; P = 0.02) because of hemorrhagic deaths. These results identify several cytogenetic subtypes of pediatric ANLL that may represent unique disease processes for which more effective early cytoreduction [-7/del(7q), t(11;V)], better supportive care measures [t(15;17)], or more effective CNS prophylaxis [inv(16)/del(16q)] would be warranted.
Cardiorenal syndrome: review of our current understanding
Authors: Savvas Hadjiphilippou, Sui Phin Kon
Journal: Journal of the Royal Society of Medicine (2015)

Renal and cardiac diseases are both prevalent and carry significant morbidity and mortality. They share common vascular risk factors and are physiologically interlinked. Dysfunction in one organ affects the other. Concurrent renal and cardiac disease is associated with a poor prognosis. This close relationship is reflected through cardiorenal syndrome. A classification system has been proposed; however, the underlying process is complex and multifactorial. Management of this syndrome focuses on improving heart function, reducing volume overload, and managing heart failure and chronic kidney disease. This, however, is challenging, limited by paucity of evidence and may lead to suboptimal therapy. Increased recognition of this syndrome should raise awareness in providing early therapy and avoiding adverse outcomes due to under-treatment. In this article, we provide an overview of our current understanding of cardiorenal syndrome, as well as its pathophysiology and treatment options.
ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells
Authors: Marwan Kwok, Nicholas Davies, Angelo Agathanggelou, Edward Smith, Ceri Oldreive, Eva Petermann, Grant Stewart, Jeff Brown, Alan Lau, Guy Pratt, Helen Parry, Malcolm Taylor, Paul Moss, Peter Hillmen, Tatjana Stankovic
Journal: Blood (2015)
Clinical Epidemiology of Chronic Obstructive Pulmonary Disease
Journal: Thorax (1990)

immune deficiency in a previously fit and now critically ill young person.Finally, the management of both the patient and, particularly, the distressed relatives is easier if the illness can be given a name.Over 50 years ago Lemierre suggested that necrobacillosis produced a syndrome "so characteristic that mistake is almost impos- sible ... It becomes relatively easy to make a diagnosis on clinical findings."3We agree, and the patient of Dr Chippindale and col- leagues is yet another illustration of this fact.The final sentence of their paper is worth rereading-and remembering.
Identification of CD25 as STAT5-Dependent Growth Regulator of Leukemic Stem Cells in Ph+ CML
Authors: Irina Sadovnik, Andrea Hoelbl-Kovacic, Harald Herrmann, Gregor Eisenwort, Sabine Cerny-Reiterer, Wolfgang Warsch, Gregor Hoermann, Georg Greiner, Katharina Blatt, Barbara Peter, Gabriele Stefanzl, Daniela Berger, Martin Bilban, Susanne Herndlhofer, Heinz Sill, Wolfgang R. Sperr, Berthold Streubel, Christine Mannhalter, Tessa L. Holyoake, Veronika Sexl, Peter Valent
Journal: Clinical Cancer Research (2015)

Abstract Purpose: In chronic myelogenous leukemia (CML), leukemic stem cells (LSC) represent a critical target of therapy. However, little is known about markers and targets expressed by LSCs. The aim of this project was to identify novel relevant markers of CML LSCs. Experimental Design: CML LSCs were examined by flow cytometry, qPCR, and various bioassays. In addition, we examined the multipotent CD25+ CML cell line KU812. Results: In contrast to normal hematopoietic stem cells, CD34+/CD38− CML LSCs expressed the IL-2 receptor alpha chain, IL-2RA (CD25). STAT5 was found to induce expression of CD25 in Lin−/Sca-1+/Kit+ stem cells in C57Bl/6 mice. Correspondingly, shRNA-induced STAT5 depletion resulted in decreased CD25 expression in KU812 cells. Moreover, the BCR/ABL1 inhibitors nilotinib and ponatinib were found to decrease STAT5 activity and CD25 expression in KU812 cells and primary CML LSCs. A CD25-targeting shRNA was found to augment proliferation of KU812 cells in vitro and their engraftment in vivo in NOD/SCID-IL-2Rγ−/− mice. In drug-screening experiments, the PI3K/mTOR blocker BEZ235 promoted the expression of STAT5 and CD25 in CML cells. Finally, we found that BEZ235 produces synergistic antineoplastic effects on CML cells when applied in combination with nilotinib or ponatinib. Conclusions: CD25 is a novel STAT5-dependent marker of CML LSCs and may be useful for LSC detection and LSC isolation in clinical practice and basic science. Moreover, CD25 serves as a growth regulator of CML LSCs, which may have biologic and clinical implications and may pave the way for the development of new more effective LSC-eradicating treatment strategies in CML. Clin Cancer Res; 22(8); 2051–61. ©2015 AACR.
Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets
Authors: Jessica R. Hitchcock, Charlotte N. Cook, Saeeda Bobat, Ewan A. Ross, Adriana Flores-Langarica, Kate L. Lowe, Mahmood Khan, C. Coral Dominguez-Medina, Sian Lax, Manuela Carvalho-Gaspar, Stefan Hubscher, G. Ed Rainger, Mark Cobbold, Christopher D. Buckley, Tim J. Mitchell, Andrea Mitchell, Nick D. Jones, N. Van Rooijen, Daniel Kirchhofer, Ian R. Henderson, David H. Adams, Steve P. Watson, Adam F. Cunningham
Journal: Journal of Clinical Investigation (2015)

Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic Salmonella Typhimurium infection, we determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin-like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. During infection, mice developed thrombi that persisted for weeks within the liver. Bacteria triggered but did not maintain this process, as thrombosis peaked at times when bacteremia was absent and bacteria in tissues were reduced by more than 90% from their peak levels. Thrombus development was triggered by an innate, TLR4-dependent inflammatory cascade that was independent of classical glycoprotein VI-mediated (GPVI-mediated) platelet activation. After infection, IFN-γ release enhanced the number of podoplanin-expressing monocytes and Kupffer cells in the hepatic parenchyma and perivascular sites and absence of TLR4, IFN-γ, or depletion of monocytic-lineage cells or CLEC-2 on platelets markedly inhibited the process. Together, our data indicate that infection-driven thrombosis follows local inflammation and upregulation of podoplanin and platelet activation. The identification of this pathway offers potential therapeutic opportunities to control the devastating consequences of infection-driven thrombosis without increasing the risk of bleeding.
Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer
Authors: Jin Peng, Junzo Hamanishi, Noriomi Matsumura, Kaoru Abiko, Kumuruz Murat, Tsukasa Baba, Ken Yamaguchi, Naoki Horikawa, Yuko Hosoe, Susan K. Murphy, Ikuo Konishi, Masaki Mandai
Journal: Cancer Research (2015)

Emerging evidence has highlighted the host immune system in modulating the patient response to chemotherapy, but the mechanism of this modulation remains unclear. The aim of this study was to analyze the effect of chemotherapy on antitumor immunity in the tumor microenvironment of ovarian cancer. Treatment of ovarian cancer cell lines with various chemotherapeutic agents resulted in upregulated expression of MHC class I and programmed cell death 1 ligand 1 (PD-L1) in a NF-κB-dependent manner and suppression of antigen-specific T-cell function in vitro. In a mouse model of ovarian cancer, treatment with paclitaxel increased CD8(+) T-cell infiltration into the tumor site, upregulated PD-L1 expression, and activated NF-κB signaling. In particular, tumor-bearing mice treated with a combination of paclitaxel and a PD-L1/PD-1 signal blockade survived longer than mice treated with paclitaxel alone. In summary, we found that chemotherapy induces local immune suppression in ovarian cancer through NF-κB-mediated PD-L1 upregulation. Thus, a combination of chemotherapy and immunotherapy targeting the PD-L1/PD-1 signaling axis may improve the antitumor response and offers a promising new treatment modality against ovarian cancer.
A collagen VI–dependent pathogenic mechanism for Hirschsprung’s disease
Authors: Rodolphe Soret, Mathilde Mennetrey, Karl F. Bergeron, Anne Dariel, Michel Neunlist, Franziska Grunder, Christophe Faure, David W. Silversides, Nicolas Pilon
Journal: Journal of Clinical Investigation (2015)

Hirschsprung's disease (HSCR) is a severe congenital anomaly of the enteric nervous system (ENS) characterized by functional intestinal obstruction due to a lack of intrinsic innervation in the distal bowel. Distal innervation deficiency results from incomplete colonization of the bowel by enteric neural crest cells (eNCCs), the ENS precursors. Here, we report the generation of a mouse model for HSCR--named Holstein--that contains an untargeted transgenic insertion upstream of the collagen-6α4 (Col6a4) gene. This insertion induces eNCC-specific upregulation of Col6a4 expression that increases total collagen VI protein levels in the extracellular matrix (ECM) surrounding both the developing and the postnatal ENS. Increased collagen VI levels during development mainly result in slower migration of eNCCs. This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promoting effects of fibronectin. Importantly, for a majority of patients in a HSCR cohort, the myenteric ganglia from the ganglionated region are also specifically surrounded by abundant collagen VI microfibrils, an outcome accentuated by Down syndrome. Collectively, our data thus unveil a clinically relevant pathogenic mechanism for HSCR that involves cell-autonomous changes in ECM composition surrounding eNCCs. Moreover, as COL6A1 and COL6A2 are on human Chr.21q, this mechanism is highly relevant to the predisposition of patients with Down syndrome to HSCR.
Focus: Syndey Tilting at the immunisation windmill
Authors: S. Chapman
Journal: BMJ (1997)

Until recently the anti-immunisation lobby in Australia has received only a fraction of the media coverage of those promoting vaccines. Most of this coverage has been concentrated in two sylvan rural regions where accusations of medicopharmaceutical conspiracies find fertile ground among enclaves of people with alternative life styles.

Last year, however, the anti-immunisation cause received a huge boost when a prestigious national TV science programme, the ABC's Quantum , broadcast two programmes that framed immunisation as a controversy with the proverbial two sides. The Australian and New Zealand Journal of Public Health published a special supplement attacking the programmes' claims. Nevertheless, …