tbuckley/cabot-search huggingface dataset:
Novel perspectives for hepatitis A virus therapy revealed by comparative analysis of hepatitis C virus and hepatitis A virus RNA replication
Authors: Katharina Esser‐Nobis, Christian Harak, Philipp Schult, Yuri Kusov, Volker Lohmann
Journal: Hepatology (2015)

Hepatitis A virus (HAV) and hepatitis C virus (HCV) are two positive‐strand RNA viruses sharing a similar biology, but causing opposing infection outcomes, with HAV always being cleared and HCV establishing persistence in the majority of infections. To gain deeper insight into determinants of replication, persistence, and treatment, we established a homogenous cell‐culture model allowing a thorough comparison of RNA replication of both viruses. By screening different human liver‐derived cell lines with subgenomic reporter replicons of HAV as well as of different HCV genotypes, we found that Huh7‐Lunet cells supported HAV‐ and HCV‐RNA replication with similar efficiency and limited interference between both replicases. HAV and HCV replicons were similarly sensitive to interferon (IFN), but differed in their ability to establish persistent replication in cell culture. In contrast to HCV, HAV replicated independently from microRNA‐122 and phosphatidylinositol 4‐kinase IIIα and β (PI4KIII). Both viruses were efficiently inhibited by cyclosporin A and NIM811, a nonimmunosuppressive analog thereof, suggesting an overlapping dependency on cyclophilins for replication. However, analysis of a broader set of inhibitors revealed that, in contrast to HCV, HAV does not depend on cyclophilin A, but rather on adenosine‐triphosphate–binding cassette transporters and FK506‐binding proteins. Finally, silibinin, but not its modified intravenous formulation, efficiently inhibited HAV genome replication in vitro , suggesting oral silibinin as a potential therapeutic option for HAV infections. Conclusion : We established a cell‐culture model enabling comparative studies on RNA replication of HAV and HCV in a homogenous cellular background with comparable replication efficiency. We thereby identified new host cell targets and potential treatment options for HAV and set the ground for future studies to unravel determinants of clearance and persistence. (H epatology 2015;62:397–408
The topical application of resorcinol can provoke a systemic allergic reaction
Authors: A. Barbaud, P. Modiano, M. Cocciale, S. Reichert, J.-L. Schmutz
Journal: British Journal of Dermatology (1996)

Journal Article The topical application of resorcinol can provoke a systemic allergic reaction Get access A. Barbaud, A. Barbaud Service de Dermatologie, Hopital Fournier, Centre Hospitalo‐Universitaire de Nancy, 36 Quai de la Bataille, 54035 Nancy, France Search for other works by this author on: Oxford Academic Google Scholar P. Modiano, P. Modiano Service de Dermatologie, Hopital Fournier, Centre Hospitalo‐Universitaire de Nancy, 36 Quai de la Bataille, 54035 Nancy, France Search for other works by this author on: Oxford Academic Google Scholar M. Cocciale, M. Cocciale Service de Dermatologie, Hopital Fournier, Centre Hospitalo‐Universitaire de Nancy, 36 Quai de la Bataille, 54035 Nancy, France Search for other works by this author on: Oxford Academic Google Scholar S. Reichert, S. Reichert Service de Dermatologie, Hopital Fournier, Centre Hospitalo‐Universitaire de Nancy, 36 Quai de la Bataille, 54035 Nancy, France Search for other works by this author on: Oxford Academic Google Scholar J.‐L. Schmutz J.‐L. Schmutz Service de Dermatologie, Hopital Fournier, Centre Hospitalo‐Universitaire de Nancy, 36 Quai de la Bataille, 54035 Nancy, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 135, Issue 6, 1 December 1996, Pages 1014–1015, https://doi.org/10.1046/j.1365-2133.1996.d01-1121.x Published: 01 December 1996
Abstract 4389: Potential role of superoxide dismutase 3 in prevention of estrogen-induced breast cancer
Authors: Hari K. Bhat, Bhupendra Singh
Journal: Cancer Research (2010)

Abstract Estrogens have been implicated in the development of human breast cancers. Literature and our studies strongly support the role of oxidative stress in estrogen-induced breast carcinogenesis. We have recently demonstrated for the first time that antioxidants vitamin C or butylated hydroxyanisole (BHA) attenuate 17β-estradiol (E2)-induced oxidative stress; increase the latency of tumor development; and, severely inhibit E2-induced breast tumor development in female ACI rats. The female ACI rat is an established animal model to study the mechanisms of E2-induced breast cancer. The objective of the present study was to identify genes that may provide an insight into the mechanism of inhibition of E2-induced breast carcinogenesis by vitamin C or BHA. Microarray analyses were performed on total RNA isolated from breast and breast tumor tissues of rats treated with E2 (3 mg, s.c.); vitamin C (1% in drinking water); BHA (0.7% in diet); vitamin C + E2 and BHA + E2 for 8 months. A number of genes were shown to be differentially expressed in breast tissue and tumor tissue of rats treated with E2 vs. other treatments. One gene of interest identified was extracellular superoxide dismutase (SOD3) that was 18-fold suppressed in mammary tumors vs. normal mammary tissue and more than 6-fold decreased in mammary tissue of E2 treated animals vs. normal age-matched controls. Protein expression data confirmed the suppression of SOD3 in mammary tissue of E2-treated rats and in mammary tumors. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. SOD3 was induced 2.9- and 2.1-fold respectively by treatments of rats with vitamin C or BHA compared to sham-treated controls. SOD3 expression was not regulated by vitamin C or BHA in the liver tissue suggesting that its expression may be target-organ specific. SOD3 is an extracellular antioxidant enzyme implicated in the prevention of oxidative stress-mediated tissue damage. Thus, SOD3 may play an important role in the prevention of breast cancer and this gene may have a great potential in the development of therapeutic strategies for the prevention of estrogen-induced neoplasia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4389.
Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease
Authors: Guy Keryer, Jose R. Pineda, Géraldine Liot, Jinho Kim, Paula Dietrich, Caroline Benstaali, Karen Smith, Fabrice P. Cordelières, Nathalie Spassky, Robert J. Ferrante, Ioannis Dragatsis, Frédéric Saudou
Journal: Journal of Clinical Investigation (2011)

Huntington disease (HD) is a devastating autosomal-dominant neurodegenerative disorder. It is caused by expansion of a CAG repeat in the first exon of the huntingtin (HTT) gene that encodes a mutant HTT protein with a polyglutamine (polyQ) expansion at the amino terminus. Here, we demonstrate that WT HTT regulates ciliogenesis by interacting through huntingtin-associated protein 1 (HAP1) with pericentriolar material 1 protein (PCM1). Loss of Htt in mouse cells impaired the retrograde trafficking of PCM1 and thereby reduced primary cilia formation. In mice, deletion of Htt in ependymal cells led to PCM1 mislocalization, alteration of the cilia layer, and hydrocephalus. Pathogenic polyQ expansion led to centrosomal accumulation of PCM1 and abnormally long primary cilia in mouse striatal cells. PCM1 accumulation in ependymal cells was associated with longer cilia and disorganized cilia layers in a mouse model of HD and in HD patients. Longer cilia resulted in alteration of the cerebrospinal fluid flow. Thus, our data indicate that WT HTT is essential for protein trafficking to the centrosome and normal ciliogenesis. In HD, hypermorphic ciliogenesis may affect signaling and neuroblast migration so as to dysregulate brain homeostasis and exacerbate disease progression.
Cells on Stems
Authors: Jane F. Desforges
Journal: New England Journal of Medicine (1978)

Blood cells, like blossoms of a floribunda, arise together from a single branch. Clinicians have long assumed that granulocytes, megakaryocytes and erythroid cells have a common origin because all three cell lines may be involved to a varying degree in the many forms of myeloproliferative disease. Studies of the marker chromosone Ph1 in chronic myelocytic leukemia support the idea since this abnormal chromosome is found in erythroid precursors, megakaryocytes and myeloid cells, but not in skin fibroblasts or lymphocytes,1 suggesting a single pluripotent stem cell that becomes committed to erythroproliferation, megakaryocyte production or granulopoiesis.There might be, in fact, a . . .
Sustained efficacy and seroconversion with the Toll-like receptor 7 agonist GS-9620 in the Woodchuck model of chronic hepatitis B
Authors: Stephan Menne, Daniel B. Tumas, Katherine H. Liu, Linta Thampi, Dalal AlDeghaither, Betty H. Baldwin, Christine A. Bellezza, Paul J. Cote, Jim Zheng, Randall Halcomb, Abigail Fosdick, Simon P. Fletcher, Stephane Daffis, Li Li, Peng Yue, Grushenka H.I. Wolfgang, Bud C. Tennant
Journal: Journal of Hepatology (2015)

New therapies for chronic hepatitis B (CHB) are urgently needed since current treatments rarely lead to cure. We evaluated whether the oral small molecule toll-like receptor (TLR7) agonist GS-9620 could induce durable antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to human hepatitis B virus (HBV).
Six professors back NICE guidance on extending use of statins
Authors: N. Hawkes
Journal: BMJ (2014)

The so called statins war triggered by two papers in The BMJ 1 2 and new guidance from the UK National Institute for Health and Care Excellence (NICE) recommending wider use of the drugs shows no signs yet of a ceasefire.

At a press briefing in London organised by the Science Media Centre, six leading professors of cardiology and epidemiology stated their conviction that the evidence from trials amply justified their confidence that the benefits of statins outweighed any risks. The authors of the two papers in The BMJ had been wrong, they said, and NICE had been right to suggest that statins should be offered to patients who didn’t have a high risk of cardiovascular events.

The Oxford University academic Rory Collins, head of the CTT (cholesterol treatment triallists) group, said that the authors of the two papers in The BMJ had withdrawn their claim that 18-20% of statin users experienced side effects. But they had not withdrawn a claim that 5% of users have myopathy. “Actually it’s 100 times less,” he said. He had earlier called for a full retraction of the papers and criticised The BMJ ’s …
Arginine Therapy
Authors: Claudia R. Morris, Sidney M. Morris, Ward Hagar, Jane van Warmerdam, Susan Claster, Diane Kepka-Lenhart, Lorenzo Machado, Frans A. Kuypers, Elliott P. Vichinsky
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Pulmonary hypertension is a life-threatening complication of sickle cell disease. L-Arginine is the nitrogen donor for synthesis of nitric oxide, a potent vasodilator that is deficient during times of sickle cell crisis. This deficiency may play a role in pulmonary hypertension. The enzyme arginase hydrolyzes arginine to ornithine and urea, and thus, it may compete with nitric oxide synthase, leading to decreased nitric oxide production. Nitric oxide therapy by inhalation has improved pulmonary hypertension associated with acute chest syndrome in sickle cell disease, and several studies demonstrate therapeutic benefits of arginine therapy for primary and secondary pulmonary hypertension. We sought to determine the effects of arginine therapy on pulmonary hypertension in patients with sickle cell disease. Arginase activity was also determined. Oral arginine produced a 15.2% mean reduction in estimated pulmonary artery systolic pressure (63.9 ± 13 to 54.2 ± 12 mm Hg, p = 0.002) after 5 days of therapy in 10 patients. Arginase activity was elevated almost twofold (p = 0.07) in patients with pulmonary hypertension and may limit arginine bioavailability. With limited treatment options and a high mortality rate for patients with sickle cell disease who develop pulmonary hypertension, arginine is a promising new therapy that warrants further investigation.
Oral Immunotherapy (OIT) Induces Clinical Tolerance in Peanut-Allergic Children
Authors: P. Varshney, S.M. Jones, L. Pons, M. Kulis, P.H. Steele, A.R. Kemper, A.M. Scurlock, T.T. Perry, A.W. Burks
Journal: Journal of Allergy and Clinical Immunology (2009)
Research Priorities for Mental Health and Psychosocial Support in Humanitarian Settings
Authors: Wietse A. Tol, Vikram Patel, Mark Tomlinson, Florence Baingana, Ananda Galappatti, Catherine Panter-Brick, Derrick Silove, Egbert Sondorp, Michael Wessells, Mark van Ommeren
Journal: PLoS Medicine (2011)

N There has been a great need to develop a research agenda to strengthen mental health and psychosocial support in humanitarian settings; prior research in this area has had limited inputs from practitioners.N We developed a consensus-based research agenda for the next ten years through inputs from an interdisciplinary group of academics, policy makers, and practitioners (n = 82) representing regions where humanitarian crises occur.N Participants reached a high level of agreement on the ten most highly prioritized research questions, which consisted of questions related to: problem analysis (four questions on identifying stressors, problems, and protective factors from the perspective of affected populations), mental health and psychosocial support interventions (three questions on sociocultural adaptation and on effectiveness of family-and school-based prevention), research and information management (two questions on assessment methods and indicators for monitoring and evaluation), and mental health and psychosocial support context (one question on whether interventions address locally perceived needs).N This research agenda emphasizes the generation of practical knowledge that could translate to immediate tangible benefits for programming in humanitarian settings, rather than addressing the key debates that have dominated the academic literature.
Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature
Authors: K Warnatz
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Retroperitoneal fibrosis (RPF) and inflammatory aneurysm of the abdominal aorta (IAAA) are regarded as two manifestations of the same disease, termed “chronic periaortitis”. <b>Objective:</b> To determine the optimal therapeutic and diagnostic approaches to IAAA. <b>Methods:</b> The outcome of medical immunosuppressive and surgical treatment of 20 patients was examined. Measurements of the C reactive protein (CRP) were compared with contrast enhanced imaging studies in the follow up of the patients. <b>Results:</b> The diameter of the periaortic mantle and its contrast enhancement improved in 13/15 (87%) patients given immunosuppressive treatment for a period of more than 6 months. Strong contrast enhancement was associated with a substantial rise in CRP, but no correlation between the CRP value and thickness of the fibrotic mass was found, even at intraindividual follow up. <b>Conclusions:</b> Immunosuppressive treatment should be included in the first line treatment of patients with RPF and should be maintained long term. Imaging studies are better than CRP measurements in the evaluation of response to treatment.
The Urokinase-Pulmonary Embolism Trial
Authors: Richard D. Sautter
Journal: JAMA (1974)

A preliminary report regarding the results of the Urokinase-Pulmonary Embolism Trial appeared in<i>JAMA</i><sup>1</sup>in 1970. The entire concept, specific aims, and results of this trial were published in<i>Circulation</i><sup>2</sup>in 1973. Still, there remains a misconception regarding the purpose of this trial and there have been gross misinterpretations of the results.<sup>3</sup> This study was not a therapeutic trial, and mortality was not used as an endpoint. The trial was<i>not</i>designed to determine whether or not urokinase therapy was more beneficial than heparin sodium therapy in the treatment of patients with pulmonary embolism, and<i>no</i>therapeutic recommendations have been made. The express purpose of the trial was to determine whether or not urokinase would accelerate the lysis of pulmonary emboli over and above the natural lytic process. Page II-15 from the article in<i>Circulation</i><sup>2</sup>contains the following paragraph. The primary objective of this controlled Trial
Abstract B41: Consider the source: Normal lung expression classifies cancer histologies, subtypes, and mutations
Authors: Matthew D. Wilkerson, Scott H. Randell, D. Neil Hayes
Journal: Clinical Cancer Research (2012)

Abstract Lung cancer's pathogenesis from normal cell to metastatic disease involves vast and complex genetic alterations. However, a patient's genetic alterations do not completely explain the pathogenic process, for tumors with the same alterations have different features and therapy responses. We hypothesized that differences in ancestral anatomical regions affect pathogenesis and as such would correlate with differences in cancer histology, subtype, and mutations. Anatomical distal and proximal region specimens from normal lungs were collected and assayed by Agilent 44K gene expression microarrays and immunohistochemistry (IHC). 271 surgically extracted lung cancers were assayed by gene expression, IHC, and gene sequencing for EGFR, KRAS, STK11, and TP53. Using the normal lung specimens, a novel classifier was created to assign cancers with an anatomical region using gene expression alone. Cancers classified as distal by gene expression were 84% adenocarcinoma, while 73% of those classified as proximal were squamous cell carcinoma (P&amp;lt;0.001). While this trend of histology and region is consistent with conventional wisdom, our results also suggest that lung cancers retain substantial gene expression from their ancestral anatomical region. Interestingly, the remainder of the cancers that did not follow this trend was explained by our previously described molecular subtypes (1, 2). Of adenocarcinomas classified proximal, 92% were in the Magnoid molecular subtype. Of squamous cell carcinomas classified distal, 60% were in the Secretory molecular subtype. Complementing microarray gene expression, TTF1 IHC protein expression was greater in distal normal specimens compared to proximal. Consistent with distal classification, adenocarcinomas had the greatest TTF1 expression. Of the squamous molecular subtypes, the Secretory subtype exhibited the greatest TTF1 expression, consistent with its distal classification. This Secretory subtype may explain previously reported TTF1-positive squamous cell carcinomas. Finally, gene mutation rates were significantly different between cancers classified as proximal and as distal. EGFR and KRAS mutation rates were greater in distal tumors compared to proximal tumors. In contrast, TP53 mutation rates were greater in proximally classified tumors. These results suggest that ancestral anatomical regions may affect lung cancer pathogenesis by modifying susceptibility to and dependency on different gene mutations. In summary, normal lung anatomical gene expression classifies lung cancers with different histologies, molecular subtypes, and gene mutation rates.
Core Textbook of Surgery
Authors: John J. Bergan
Journal: JAMA (1972)

As surgery becomes responsive to a constricted medical curriculum, surgical educators need to rework their own approach toward teaching, so that principles are emphasized and the natural history of surgical disease is stressed. This must be done at the expense of technique and technical manipulation. Recognizing this, and realizing that conventional textbooks are too weighty, too long, too detailed for today's student, the authors of this book have attempted to present only the essentials to be included in a brief surgical curriculum. The book has merit. It is short, devoid of illustration, and is the better for this omission. Its finest sections, including those on surgical endocrinology by Egdahl and vascular disease by Mannick, combine basic topics from subjects conventionally separated and thus provide a common background for the student. As such, these portions are a true core. In some other areas, authors have provided less depth, less integration of
Effect of Diabetes on Glucoregulation: From glucose transporters to glucose metabolism in vivo
Authors: Amira Klip, André Marette, Dimitrios Dimitrakoudis, Toolsie Ramlal, Adria Giacca, Zhi Q Shi, Mladen Vranic
Journal: Diabetes Care (1992)

Peripheral resistance to insulin is a prominent feature of both insulin-dependent and non-insulin-dependent diabetes. Skeletal muscle is the primary site responsible for decreased insulin-induced glucose utilization in diabetic subjects. Glucose transport is the rate-limiting step for glucose utilization in muscle, and that cellular process is defective in human and animal diabetes. The transport of glucose across the muscle cell plasma membrane is mediated by glucose transporter proteins, and two isoforms (GLUT1 and GLUT4) are expressed in muscle. Insulin acutely increases glucose transport in muscle by selectively stimulating the recruitment of the GLUT4 transporter (but not GLUT1) from an intracellular pool to the plasma membrane. In skeletal muscles of streptozocin-induced diabetic rats, there is a decreased GLUT4 protein content in intracellular and plasma membranes. In these rats, insulin induced the mobilization of GLUT4 from the internal pool, but the incorporation of the transporter protein into the plasma membrane is diminished. Conversely, the content of the GLUT1 transporter increases in the plasma membrane of these diabetic rats. Normalization of glycemia with phlorizin fully restores the amount of GLUT1 and GLUT4 proteins to normal levels in the plasma membrane without altering insulin levels. This suggests that glycemia regulates the number of glucose transporters at the cell surface, GLUT1 varying directly and GLUT4 inversely, to glycemia. The regulatory role of glycemia also can be seen in diabetic dogs in vivo, where correction of hyperglycemia with phlorizin restores, at least in part, the defective metabolic clearance rate of glucose seen in these animals. In addition to acutely stimulating glucose transport in muscle, insulin controls exercise- and possibly stress-mediated glucose uptake in vivo, by preventing hyperglycemia and by restraining the effects of catecholamines on lipolysis and/or muscle glycogenolysis. Finally, we postulated a neural pathway that requires the permissive effect of insulin to increase glucose uptake by the muscle. Thus, insulin, glucose, and neural pathways regulate muscle glucose utilization in vivo and are, therefore, important determinants of glucoregulation in diabetes.
The association between vitamin D status and the rate of exacerbations requiring oral corticosteroids in preschool children with recurrent wheezing
Authors: Avraham Beigelman, Robert S. Zeiger, David Mauger, Robert C. Strunk, Daniel J. Jackson, Fernando D. Martinez, Wayne J. Morgan, Ronina Covar, Stanley J. Szefler, Lynn M. Taussig, Leonard B. Bacharier
Journal: Journal of Allergy and Clinical Immunology (2014)