tbuckley/cabot-search huggingface dataset:
The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage
Authors: Tatiana Varanita, Maria Eugenia Soriano, Vanina Romanello, Tania Zaglia, Rubén Quintana-Cabrera, Martina Semenzato, Roberta Menabò, Veronica Costa, Gabriele Civiletto, Paola Pesce, Carlo Viscomi, Massimo Zeviani, Fabio Di Lisa, Marco Mongillo, Marco Sandri, Luca Scorrano
Journal: Cell Metabolism (2015)

Highlights•Mice with controlled Opa1 overexpression are viable and grow normally•Opa1 protects from muscular atrophy, heart and brain ischemia, and liver apoptosis•Opa1 reduces ROS production and cytochrome c release•Opa1-controlled cristae remodeling is a targetable component of tissue damageSummaryMitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo.Graphical abstract
Mammography and the politics of randomised controlled trials Commentary: The public has a role to play in translating evidence into practice Commentary: Why are researchers surprised when there is not a smooth transition from research into practice?
Authors: J. Wells, G. J Ong, H. Bastian
Journal: BMJ (1998)

# Mammography and the politics of randomised controlled trials {#article-title-2}

The purpose of screening mammography is to reduce mortality in women who develop breast cancer by detecting it at a stage when treatment is most likely to be effective. Mammography has been more extensively evaluated by randomised controlled trials than any other screening intervention but its effectiveness in some groups of women remains controversial.

x Ray examination of the breast has been used since the beginning of this century; initially for diagnosis and later for the detection of non-palpable lesions. By the early 1960s results from mammography had been shown to be sufficiently reliable to prompt the United States National Cancer Institute to begin a trial of its use as a screening procedure. Organisations in the United States involved in assessing the effectiveness of mammography are described in the box.

### Summary points

Randomised controlled trials of the effectiveness of screening mammography have found that it significantly reduces mortality in women over 50 but that the benefit is smaller, and the associated harm is greater, in younger women

In the United States many organisations have issued guidelines on screening for women aged 40-49, some groups recommend that they should be screened regularly and others that they should not

In January 1997 a consensus conference convened by the National Cancer Institute did not advise routine screening but recommended that women reach their own decision in consultation with their doctor

Many politicians, professional and voluntary groups, and individuals (including some healthcare professionals, journalists, women with breast cancer, and researchers) disagreed with this recommendation, and pressure was exerted on the National Cancer Institute to recommend regular screening for all women aged 40-49; in March 1997 the institute issued guidelines recommending regular screening for this age group

Political involvement and public expectations can impede the appropriate translation of research findings into clinical practice

### US organisations involved in assessing the effectiveness of mammography

National Institutes of Health …
Abstract 15938: Identification of a Novel Disease Gene for Early Onset Atherosclerosis, Diabetes and Metabolic Syndrome by Whole Exome Sequencing and Linkage Analysis
Authors: Ali R. Keramati, Mohsen Fathzadeh, Rajvir Singha, Murim Choia, Saeed Faramarzia, Shrikant Manea, Mohammad Kasaeib, Mohammad A. Babaee Bigib, Reza Malekzadeh, Adalat Hosseinian, Masoud Babaie, Richard P. Liftona, Arya Mania
Journal: Circulation (2013)

Ali R. Keramati, 2013 Finalist and Presenting Author
A Study of 800 Abnormal Electrocardiograms and Associated Clinical Conditions
Authors: M. A. Mortensen
Journal: Annals of Internal Medicine (1933)

Article1 April 1933A Study of 800 Abnormal Electrocardiograms and Associated Clinical ConditionsM. A. MORTENSEN, M.D., F.A.C.P.M. A. MORTENSEN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-6-10-1308 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of this communication is to emphasize the practical value of the electrocardiogram for the study of cardiovascular diseases. The tracing is based on the electrical reactions of the heart muscle during each complete cycle of action and rest. The evolution of our knowledge of the cardiogram dates back to Matteuci, who in 1843 reported the existence of reactions or currents originating in the heart muscle. The studies of Engelman, Marey, Burdon, Sanderson and Page, Gaskell, Kölliker and Mueller, and Waller, led up to the development of the string galvanometer by Einthoven in 1903. Since then there has been...References PARDEE HE: Significance of electrocardiogram with large Q in Lead III, Arch. Int. Med., 1930, xlvi, 470-481. CrossrefGoogle Scholar MUSSERBARTON JHJC: Familial tendency of coronary disease, Am. Heart Jr., 1931, vii, 45-51. CrossrefGoogle Scholar BARNESWHITTEN ARMB: Study of T-wave negativity in predominant ventricular strain, Am. Heart Jr., 1929, v, 14-67. CrossrefGoogle Scholar WOLFERTH CC: Diseases of the heart and blood vessels, Prog. Med., 1931, iii, 109-173. Google Scholar SCOTT RW: Clinical aspects of arteriosclerosis, Am. Heart Jr., 1932, vii, 292-304. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Battle Creek, Michigan*Read at the meeting of the American College of Physicians, San Francisco, California, April 7, 1932. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDie Coronarerkrankungen. Coronarinsuffizienz, Angina pectoris und HerzinfarktErbbiologie und Erbpathologie des KreislaufapparatesInfektiös-Toxische Myokardschädigung im Elektrokardiogramm 1 April 1933Volume 6, Issue 10Page: 1308-1314KeywordsCardiovascular diseasesElectrocardiographyMyocardium Issue Published: 1 April 1933 PDF downloadLoading ...
My Love and Back Surgery
Authors: Maurice Kilwein Guevara
Journal: JAMA (1998)

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
Abstract 957: The ALK inhibitor LDK378 overcomes crizotinib resistance in non-small cell lung cancer
Authors: Luc Friboulet, Nanxin Li, Ryohei Katayama, Christian C. Lee, Justin F. Gainor, Adam S. Crystal, Pierre-Yves Michellys, Mark M. Awad, Noriko Yanagitani, Sungjoon Kim, AnneMarie Pferdekamper, Jie Li, Shailaja Kasibhatla, Frank Sun, Xiuying Sun, Su Hua, Peter McNamara, Sidra Mahmood, Elizabeth L. Lockerman, Naoya Fujita, Makoto Nishio, Jennifer L. Harris, Alice T. Shaw, Jeffrey A. Engelman
Journal: Cancer Research (2014)

Abstract Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements are sensitive to the ALK tyrosine kinase inhibitor (TKI) crizotinib. However, these cancers invariably relapse due to the development of resistance, and approximately 1/3 of such cancers develop resistance mutations within the ALK tyrosine kinase domain. Here we report the preclinical evaluation of the next-generation ALK TKI, LDK378 in the setting of crizotinib resistance. Using EML4-ALK mutant Ba/F3 cellular models, in vivo models of acquired resistance to crizotinib, and novel cell lines established from biopsies of crizotinib-resistant NSCLC patients, we have examined the efficacy of LDK378 in crizotinib-naïve and -resistant ALK-positive cancers. These studies reveal that LDK378 is more potent than crizotinib and effectively overcomes resistance in vitro and in vivo. In particular, LDK378 inhibits ALK harboring crizotinib resistance mutations, including L1196M, G1269A, I1171T and S1206Y. Cell lines derived from crizotinib-resistant biopsies were sensitive to LDK378, including one that did not harbor an ALK resistance mutation and was also sensitive to crizotinib, suggesting that some crizotinib-resistant cancers with wildtype ALK are still sensitive to complete ALK inhibition. We observed that LDK378 did not effectively overcome two crizotinib-resistant ALK mutations, G1202R and F1174C ALK, and mutations in one of these residues was identified in 5 out of 11 biopsies from patients with acquired resistance to LDK378. Altogether our results demonstrate that LDK378 can overcome many mechanisms of crizotinib resistance, consistent with emerging clinical data showing marked efficacy of LDK378 in patients with crizotinib-resistant disease. Citation Format: Luc Friboulet, Nanxin Li, Ryohei Katayama, Christian C. Lee, Justin F. Gainor, Adam S. Crystal, Pierre-Yves Michellys, Mark M. Awad, Noriko Yanagitani, Sungjoon Kim, AnneMarie Pferdekamper, Jie Li, Shailaja Kasibhatla, Frank Sun, Xiuying Sun, Su Hua, Peter McNamara, Sidra Mahmood, Elizabeth L. Lockerman, Naoya Fujita, Makoto Nishio, Jennifer L. Harris, Alice T. Shaw, Jeffrey A. Engelman. The ALK inhibitor LDK378 overcomes crizotinib resistance in non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 957. doi:10.1158/1538-7445.AM2014-957
Abstract 630: Induction of anti-melanoma immunity after intralesional ablative therapy
Authors: Hao Liu, Krithika Kodumudi, Amy Weber, Amod A. Sarnaik, Shari Pilon-Thomas
Journal: Cancer Research (2014)

Abstract Immunotherapeutic strategies incorporating intralesional (IL) ablative therapy to elicit a tumor specific immune response are under investigation as a non-surgical option to induce tumor regression of cutaneous neoplasms. Rose Bengal (RB) is a water-soluble xanthene dye that was originally used as an intravenous liver diagnostic and is in use by ophthalmologists to stain damaged cells in the eye. In murine models of breast cancer and melanoma, we have shown that IL injection of PV-10 (10% RB in saline solution) leads to ablation of injected tumors and regression of non-injected bystander tumors. In these models, increased anti-tumor T cell responses were measured, supporting the induction of systemic anti-tumor immunity after tumor ablation with PV-10. In our ongoing phase I clinical trial exploring melanoma regression in patients, IL PV-10 has led to a significant decrease of melA positive melanoma cells in the biopsies of both PV10-injected and non-injected lesions. This regression correlated with increased circulating CD3+T cells (p=0.03) in peripheral blood mononuclear cells (PBMC). T cells purified from PBMC from a melanoma patient produced increased IFN-gamma in response to autologous tumor after treatment with PV-10. Ex vivo models implemented to investigate this phenomenon indicate that the cytotoxicity induced by PV-10 is not apoptosis-dependent as evidenced by Annexin staining of melanoma cells following PV-10 treatment. PV-10 directly induced necrosis of melanoma cells at 50 uM, but was not toxic to healthy fibroblasts at the same dose. Further preclinical translational testing has shown that treatment of murine B16 cells with PV-10 leads to release of HMGB1, a soluble Damage Associated Molecule Pattern (DAMP) that is important for activation of dendritic cells (DCs). In the murine B16 melanoma model, there is a significant increase in the number of DCs infiltrating the tumor-draining lymph nodes after IL injection of PV-10. These findings suggest that PV-10 treatment leads to the release of DC activating factors and DC recruitment. Further studies to determine the role of PV-10 on T cell activation are ongoing. In sum, these clinical and preclinical results increase our understanding of the cytotoxic and immunological mechanisms that may play a role in systemic immunity induced by PV-10 tumor ablation. Citation Format: Hao Liu, Krithika Kodumudi, Amy Weber, Amod A. Sarnaik, Shari Pilon-Thomas. Induction of anti-melanoma immunity after intralesional ablative therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 630. doi:10.1158/1538-7445.AM2014-630
Handbook of Chest Surgery for Nurses
Authors: J. Leigh Collis, Lettie Elizabeth Mabbit
Journal: JAMA (1952)

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
TRPV1 Antagonism in Refractory Chronic Cough: A Double Blind Randomised Controlled Trial
Authors: Saifudin Khalid, Robert Murdoch, Amy Newlands, Kevin Smart, Angela Kelsall, Kimberley Holt, Rachel Dockry, Ashley Woodcock, Jaclyn A. Smith
Journal: Journal of Allergy and Clinical Immunology (2014)
FGFR1 is fused to the centrosome-associated proteinCEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33)
Authors: Géraldine Guasch, Gary J. Mack, Cornel Popovici, Nicole Dastugue, Daniel Birnbaum, Jérome B. Rattner, Marie-Josèphe Pébusque
Journal: Blood (2000)
G-quadruplex stabilization by anthraquinone-peptide conjugates
Authors: Claudia Sissi, Lorena Lucatello, Sergio Alfredo Cadamuro, Giuseppe Zagotto, Manlio Palumbo, Keith Fox
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4994 

Telomerase is an acknowledged potential target for cancer chemotherapy. An accepted means to inhibit this enzyme is to induce and stabilize telomere G-quartet formation using low molecular weight compounds. Several molecules are known to interact efficiently with different nucleic acid structures. The real challenge is to design ligands that selectively recognise G-quadruplex DNA without exhibiting appreciable affinity for other structural arrangements (in particular double stranded DNA) of nucleic acids in the cell. In this work, we analysed the ligand-mediated stability of G-quadruplexes using synthetic oligonucleotides containing a fluoro phore (fluorescein) at the 5’-end and a quencher (MethylRed) at the 3’-end. When these sequences fold into an intramolecular G-quadruplex, fluorescein and MethylRed are in close proximity and the fluorescence is quenched, whereas, when DNA denaturation occurs, they are separated and there is a large increase in the fluorescence signal. The temperature at which this process takes place (Tm) is related to G-quadruplex stability, and ligands which bind to this structure increase the melting temperature. The observed changes provide a reliable indication of the G-quadruplex affinity for different compounds. In this connection, we synthesised a small library of anthraquinone-amino acid/peptide conjugates symmetrically di-substituted at positions 2,6 or 2,7 and exhibiting different charge, lipophilicity and bulkiness. The concentration-dependent effects of these ligands on the thermal stability of the G quadruplex structure, formed by the human telomere sequence, were investigated. The most effective anthraquinones were studied under different salt conditions and in the presence of G quadruplex structures containing modified loops. Our systematic analysis allowed us to define structure-activity relationships. Indeed, it emerged that the direction of the amide linkage between the linker and the anthraquinone, the position of the side chains, and the nature of the aminoacid(s) in the side chains play a significant role in modulating G-quadruplex stability. Conversely, the nature of the oligonucleotide loops does not substantially alter the strength of the drug-DNA complex. These results will help in the rational design of more efficient and selective G-quadruplex stabilizers, which are endowed with antiproliferative effects.
1035. Syncytia Induction Enhances the Oncolytic Potential of Vesicular Stomatitis Virus in Virotherapy for Cancer
Authors: Oliver Ebert, Katsunori Shinozaki, Chryssanthi Kournioti, Man-Seong Park, Adolfo Garcia-Sastre, Savio L. C. Woo
Journal: Molecular Therapy (2004)

Vesicular stomatitis virus (VSV) selectively replicates in tumor but not in normal cells, and is being developed as an oncolytic agent for cancer therapy. Here we report the construction of a recombinant VSV capable of inducing syncytia formation between tumor cells through membrane fusion at neutral pH, which led to enhanced oncolytic properties against multi-focal hepatocellular carcinoma (HCC) in the livers of immune-competent rats. Recombinant VSV vectors were constructed by insertion into its genome a transcription unit expressing a control or fusion protein derived from Newcastle disease virus. In vitro characterization of the recombinant fusogenic VSV vector on human and rat HCC cells showed extensive syncytia formation and significantly enhanced cytotoxic effects. In vivo, administration of fusogenic VSV into the hepatic artery of Buffalo rats bearing syngeneic multi-focal HCC lesions in their livers resulted in syncytia formation exclusively within the tumors, as well as no collateral damage to the neighboring hepatic parenchyma. The fusogenic VSV also conferred a significant survival advantage over a non-fusogenic control virus in the treated animals (p=0.0078, log-rank test). The results suggest that fusogenic VSV can be developed into an effective and safe therapeutic agent for cancer treatment in patients, including those with multi-focal HCC in the liver.
Options for managing low grade cervical abnormalities detected at screening: cost effectiveness study
Authors: Maggie Cruickshank, Graeme Murray, David Parkin, Louise Smart, Eric Walker, Norman Waugh, Mark Avis, Claire Chilvers, Katherine Fielding, Rob Hammond, David Jenkins, Jane Johnson, Keith Neal, Ian Russell, Rashmi Seth, Dave Whynes, Ian Duncan, Alistair Robertson, Julian Little, Linda Sharp, Leslie Walker, Breda Anthony, Sarah Bell, Adrienne Bowie, Katrina Brown, Joe Brown, Kheng Chew, Claire Cochran, Seonaidh Cotton, Jeannie Dean, Kate Dunn, Jane Edwards, David Evans, Julie Fenty, Al Finlayson, Marie Gallagher, Nicola Gray, Maureen Heddle, Alison Innes, Debbie Jobson, Mandy Keillor, Jayne MacGregor, Sheona Mackenzie, Amanda Mackie, Gladys McPherson, Ike Okorocha, Morag Reilly, Joan Rodgers, Alison Thornton, Rachel Yeats, Lindyanne Alexander, Lindsey Buchanan, Susan Henderson, Tine Iterbeke, Susanneke Lucas, Gillian Manderson, Sheila Nicol, Gael Reid, Carol Robinson, Trish Sandilands, Marg Adrian, Ahmed Al-Sahab, Elaine Bentley, Hazel Brook, Claire Bushby, Rita Cannon, Brenda Cooper, Ruth Dowell, Mark Dunderdale, E. Gabrawi, Li Guo, Lisa Heideman, Steve Jones, Salli Lawson, Zoe Philips, Christopher Platt, Shakuntala Prabhakaran, John Rippin, Rose Thompson, Elizabeth Williams, Claire Woolley, Massoud Boroujerdi, Kirsten Harrild, John Norrie, Nicholas Day, Theresa Marteau, Mahesh Parmar, Julietta Patnick, Ciaran Woodman, Doug Altman, Sue Moss, Michael Wells
Journal: BMJ (2009)

Objective To estimate the cost effectiveness of alternative methods of managing low grade cervical cytological abnormalities detected at routine screening.