tbuckley/cabot-search huggingface dataset:
Induction of p53R2 by dFdCyd does not prevent R2 expression
Authors: Joe Barber, Mike Im, Donna S. Shewach
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2972 

Gemcitabine (2’, 2’-difluoro-2’-deoxycytidine; dFdCyd) is a clinically effective chemotherapeutic agent and radiation sensitizer. These properties require intracellular phosphorylation of dFdCyd to its di- and triphosphate metabolites. dFdCyd triphosphate is incorporated into DNA and is primarily responsible for cytotoxicity, whereas inhibition of ribonucleotide reductase by dFdCyd diphosphate correlates with radiosensitization. Ribonucleotide reductase is a tetrameric protein consisting of two regulatory subunits (R1) and two catalytic subunits (R2). Recently, a novel ribonucleotide reductase subunit, p53R2, was discovered. p53R2 is a homologue of the ribonucleotide reductase R2 subunit, and it was shown to be induced in a p53-dependent fashion following DNA damage by ionizing radiation with a concomitant decrease in R2. These results suggested that ribonucleotide reductase utilizes R2 to produce dNTPs for DNA replication whereas p53R2 is necessary to produce dNTPs for repair of DNA damage. We wished to determine whether other DNA damaging agents, such as dFdCyd, would produce effects similar to ionizing radiation on expression of p53R2 and R2. In addition, we determined whether dFdCyd could produce DNA damage in the form of DNA double strand breaks (DSBs) by immunostaining for phosphorylated H2AX (γ-H2AX), a novel histone that is rapidly phosphorylated and accumulated at the site of DSBs to form discrete foci. Wild-type p53 expressing MCF-7 cells were incubated for 24 hr with dFdCyd at the IC50 or IC90 or treated with 5 Gy. Cells were then evaluated for expression of p53, p53R2 and R2 by Western blot analysis or γ-H2AX foci formation by confocal microscopy. The results demonstrated that p53 and p53R2 expression were induced slowly during the 24 hr incubation with dFdCyd, with persistent expression of R2. In contrast, cells treated with 5 Gy exhibited induction of p53 and p53R2 within 2 hr, and expression of these proteins was apparent for at least 24 hr afterward. By 4 hr after irradiation expression of R2 decreased dramatically. Measurement of the formation of γ-H2AX foci demonstrated a dose-dependent increase in DSBs following a 24 hr incubation with dFdCyd at concentrations ranging from IC25 to IC90. In response to 5 Gy, γ-H2AX foci were observed within 15 min and exceeded the number that formed after 24 hr incubation with dFdCyd at the IC90. These results demonstrate that cytotoxic concentrations of dFdCyd produced significant DNA damage and induced p53R2 expression, but did not prevent expression of R2. It is possible that the higher amount of DNA damage produced by ionizing radiation was responsible for the more rapid induction of p53R2 as well as the decrease in R2 expression. These data suggest that both p53R2 and R2 participate in maintenance of dNTP pools following treatment of cells with dFdCyd.
REPORT OF COMMITTEE ON CARDIAC CATHETERIZATION AND ANGIOCARDIOGRAPHY
Authors: Andre Cournand, Richard J. Bing, Lewis Dexter, Charles Dotter, Louis N. Katz, James V. Warren, Earl Wood
Journal: Annals of Internal Medicine (1953)

Editorial1 May 1953REPORT OF COMMITTEE ON CARDIAC CATHETERIZATION AND ANGIOCARDIOGRAPHYANDRE COURNAND, M.D., Chairman, RICHARD J. BING, M.D., LEWIS DEXTER, M.D., CHARLES DOTTER, M.D., LOUIS N. KATZ, M.D., JAMES V. WARREN, M.D., EARL WOOD, M.D.ANDRE COURNAND, M.D., ChairmanSearch for more papers by this author, RICHARD J. BING, M.D.Search for more papers by this author, LEWIS DEXTER, M.D.Search for more papers by this author, CHARLES DOTTER, M.D.Search for more papers by this author, LOUIS N. KATZ, M.D.Search for more papers by this author, JAMES V. WARREN, M.D.Search for more papers by this author, EARL WOOD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-38-5-1081 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptINTRODUCTIONCardiac, catheterization and angiocardiography are two methods which are being widely used for the investigation of acquired and congenital heart disease. Since both of these procedures entail some risk to the patient, the Scientific Council of the American Heart Association deemed it advisable to establish a committee to evaluate this risk and to recommend methods to minimize it. The constituent members of the committee were chosen on the basis of their contributions to the evolution of these methods and experience in their application.METHOD OF GATHERING INFORMATION FOR THIS REPORTTwo possible methods of gathering the necessary information were suggested:... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Published at the request of the American Heart Association. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHerzstillstand bei diagnostischen und therapeutischen EingriffenComparative analysis of the Starr-Edwards ball valve, the Kay-Suzuki disc valve and transplant valves in the surgical correction of aortic valve diseaseCardiovascular SystemPrevention of infection in patients with cardiovascular disease 1 May 1953Volume 38, Issue 5Page: 1081-1087KeywordsAngiocardiographyCatheterizationCongenital heart diseaseHeartHeart diseases ePublished: 1 December 2008 Issue Published: 1 May 1953 PDF downloadLoading ...
Abstract 3050: Human rectal carcinoid tumors highly express DCLK1, a putative cancer stem cell marker
Authors: Yu Ikezono, Hironori Koga, Mitsuhiko Abe, Takafumi Yoshida, Toru Nakamura, Jun Akiba, Hirohisa Yano, Osamu Tsuruta, Takuji Torimura, Michio Sata
Journal: Cancer Research (2014)

Abstract Background and Aim: Doublecortin-like kinase 1 (Dclk1) is known to regulate neuronal differentiation, migration, and neurogenesis (Shu et al., Neuron 2006). Accumulating evidence suggests that the protein is a putative marker for intestinal and pancreatic stem cells, including cancer stem cells (CSCs) of those organs (Gagliardi et al., Pathol Res 2012, Nakanishi et al., Nat Genet 2013, Bailey et al., Gastroenterology 2013). Since carcinoid tumor is defined as a neuroendocrine tumor, we assessed whether or not the Dclk1 protein, a marker of CSC, was expressed in human rectal carcinoid tumor tissues. Patients and Methods: Eighteen patients (9 male, 9 female; mean age, 51) with rectal carcinoid tumors were included in this study. Informed consent was obtained from all of the patients. The tumors were safely resected by endoscopic mucosal resection (EMR) method between 2003 and 2012 in the Kurume University Hospital. Mean diameter of the tumors was 5.4 mm (range, 2.0-8.0 mm). Immunohistochemical staining was performed to examine the Dclk1 protein expression, accompanied by the staining for the commonly-used neuroendocrine markers synaptophysin, chromogranin A, and CD56. The immune-reactivity was evaluated according to the following criteria: the intensity of staining was scored in each specimen on a scale of 0 to 3, in which 0 = negative staining, 1 = weakly positive staining, 2 = moderately positive staining, and 3 = strongly positive staining. The extent to which positive cells were seen in each specimen (‘‘extent of distribution’’ of positive cells) was estimated on a scale of 0 to 2, in which 0 = positive staining in 0% to 20% of cells; 1, in 21% to 60%; and 2, in 61% to 100%. Sum of the scores was calculated for each specimen. Results: The total score for Dclk1, synaptophysin, CD56, and chromogranin A was 87/90, 86/90, 60/90, and 34/90, respectively. Conclusions: Human rectal caricinoid tumor highly expressed Dclk1, and the high expression rate indicated that the protein expression was a novel feature for the neuroendocrine tumor. It is suggested that Dclk1 is a potential marker of not only CSCs but also non-epithelial tumors, such as carcinoid tumor, regulating crucial tumor cell behaviors. Citation Format: Yu Ikezono, Hironori Koga, Mitsuhiko Abe, Takafumi Yoshida, Toru Nakamura, Jun Akiba, Hirohisa Yano, Osamu Tsuruta, Takuji Torimura, Michio Sata. Human rectal carcinoid tumors highly express DCLK1, a putative cancer stem cell marker. [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 3050. doi:10.1158/1538-7445.AM2014-3050
Broadly Neutralizing Antibodies and the Development of Vaccines
Authors: Barton F. Haynes, Todd Bradley
Journal: JAMA (2015)

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
Doctors launch website on patients' experiences of illness
Authors: Rhona MacDonald
Journal: BMJ (2001)

The founder of a UK medical bulletin and an Oxford GP who had cancer have launched a website offering personal and informative health data for people with serious illnesses.

The database of patient experiences of illness (DIPEx) is the brainchild of Andrew Herxheimer, former editor of the Drug and Therapeutics Bulletin , and GP Ann McPherson, who was diagnosed with breast cancer five years ago.

The site will answer questions about what a diagnosis means and what the person should do about it, in …
Complications following percutaneous liver biopsy
Authors: F. Piccinino, E. Sagnelli, G. Pasquale, G. Giusti, A. Battocchia, M. Bernardi, R. Bertolazzi, F.B. Bianchi, E. Brunelli, G. Budillon, L. Buscarini, A. Cargnel, G. Carrara, N. Carulli, L. Caruso, V. Cataldi, G. Celle, L. Chiandussi, L. Chiesa, M. Colombo, M. Coltorti, C. De Bac, C. Del Vecchio Blanco, G. Di Marco, F. Fiaccadori, M.G. Filippazzo, F. Fornari, A. Francavilla, M. Frezza, V. Gallo, V. Galvani, T. Givatto, C. Iannuzzi, C.M. Izzo, S. Le Moli, G. Longo, G. Magnani, M. Manai, F. Manenti, O. Manghisi, G. Manzillo, G. Marenco, F. Miglio, G. Molino, P.G. Mosca, R. Moschetta, C. Panella, G. Panichi, G. Parrilli, G. Pastore, C. Peluso, A. Picciotto, G. Pilleri, E. Pisi, M. Ponz de Leon, M. Rago, G. Raimondo, G. Realdi, M. Rizzetto, A. Rizzo, G. Ronchi, F. Rossi Fanelli, G. Ruggiero, N. Russo, A. Satta, D.E. Sansonno, C. Struglia, P. Tolentino, F. Tremolada, C. Trischitta, G. Verme, P. Viganò, G. Visco, P. Zivelonghi
Journal: Journal of Hepatology (1986)
A novel mutation in the <i>SLC40A1</i> gene associated with reduced iron export <i>in vitro</i>
Authors: María‐Isabel Moreno‐Carralero, Juan‐Antonio Muñoz‐Muñoz, Nuria Cuadrado‐Grande, Rafaela López‐Rodríguez, María José Hernández‐Alfaro, Alejandro del‐Castillo‐Rueda, Rafael Enríquez‐de‐Salamanca, Manuel Méndez, María‐Josefa Morán‐Jiménez
Journal: American Journal of Hematology (2014)

Ferroportin disease is an inherited disorder of iron metabolism and is caused by mutations in the ferroportin gene (SLC40A1). We present a patient with hyperferritinemia, iron overload in the liver with reticuloendothelial distribution and also in the spleen, and under treatment with erythropheresis. A molecular study of the genes involved in iron metabolism (HFE, HJV, HAMP, TFR2, SLC40A1) was undertaken. In vitro functional studies of the novel mutation found in the SLC40A1 gene was performed. The patient was heterozygous for a novel mutation, c.386T>C (p.L129P) in the SLC40A1 gene; some of his relatives were also heterozygous for this mutation. In vitro functional studies of the L129P mutation on ferroportin showed it impairs its capacity to export iron from cells but does not alter its sensitivity to hepcidin. These findings and the iron overload phenotype of the patient suggest that the novel mutation c.386T>C (p.L129P) in the SLC40A1 gene has incomplete penetrance and causes the classical form of ferroportin disease.
The Treatment of Neurosyphilis
Authors: H. C. Solomon
Journal: Annals of Internal Medicine (1929)

Article1 November 1929The Treatment of NeurosyphilisH. C. SOLOMON, M.D.H. C. SOLOMON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-5-447 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Excerpt1. It is now possible to obtain an apparent arrest in all forms of neurosyphilis.2. Not all cases of any form or variety of neurosyphilis can be arrested.3. Febrile methods and tryparsamide are the most effective means available in the treatment of neurosyphilis. Intraventricular, intracistern, intraspinal serum injections, as well as arsphenamin, bismuth, mercury, and iodid, are of secondary importance.4. The arrest of late and advanced and malignant types of neurosyphilis give strong evidence that when cases are treated earlier they can be arrested before great damage has occurred.5. Improvement in our methods of treatment is... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass.*Read before the Boston Meeting of the American College of Physicians, April 10, 1929. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1929Volume 3, Issue 5Page: 447-451KeywordsBismuth Issue Published: 1 November 1929 PDF downloadLoading ...
The relevance of patch testing in peristomal dermatitis
Authors: F. Al-Niaimi, M. Beck, N. Almaani, V. Samarasinghe, J. Williams, C. Lyon
Journal: British Journal of Dermatology (2012)

Journal Article The relevance of patch testing in peristomal dermatitis Get access F. Al‐Niaimi, F. Al‐Niaimi Department of Dermatology, Salford Royal Foundation Trust, Manchester, U.K Firas Al‐Niaimi. E‐mail: firas55@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar M. Beck, M. Beck Department of Dermatology, Salford Royal Foundation Trust, Manchester, U.K Search for other works by this author on: Oxford Academic Google Scholar N. Almaani, N. Almaani Department of Dermatology, St John’s Institute of Dermatology, London, U.K Search for other works by this author on: Oxford Academic Google Scholar V. Samarasinghe, V. Samarasinghe Department of Dermatology, Salford Royal Foundation Trust, Manchester, U.K Search for other works by this author on: Oxford Academic Google Scholar J. Williams, J. Williams Department of Dermatology, Salford Royal Foundation Trust, Manchester, U.K Search for other works by this author on: Oxford Academic Google Scholar C. Lyon C. Lyon Department of Dermatology, York Hospital, York, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 1, 1 July 2012, Pages 103–109, https://doi.org/10.1111/j.1365-2133.2012.10925.x Published: 01 July 2012 Article history Accepted: 26 February 2012 Published: 01 July 2012
Abstract 13271: Incidence of Stent Complications detected by Optical Coherence Tomography and their Clinical Significance: One Year Follow up Study
Authors: Tsunenari Soeda, Seung-Jung Park, Yangsoo Jang, Stephen Lee, Owen C Raffel, So-Yeon Choi, Stanley Chia, Tomonori Itoh, Catalin Toma, Haibo Jia, Yoshiyasu Minami, Rocco Vergallo, Jinwey Tian, Sining Hu, Hang Lee, Bo Yu, Shiro Uemura, Yoshihiko Saito, Ik-Kyung Jang
Journal: Circulation (2014)

Introduction: Optical coherence tomography (OCT) was introduced to optimize percutaneous coronary intervention (PCI). Due to its unprecedented resolution, complications are frequently visualized. The exact incidence and clinical significance of these OCT detected complications are unknown. Object: The aims of this study were 1) to evaluate the incidence of acute stent complications by OCT, 2) to correlate these complications with clinical outcome at 1 year, and 3) to identify the OCT predictors for major adverse cardiac events (MACE) including death, acute myocardial infarction (AMI), stent thrombosis, and target lesion revascularizations (TLR). Methods and Results: A total of 409 patients with 473 drug eluting stents (DES) who had post stent OCT imaging were included in this study. The incidence of stent edge dissection was 36.4% and of intra stent dissection was 72.3%. Incomplete stent apposition was detected in 36.4% of stents. The incidence of smooth protrusion, fibrous flap or disrupted fibrous plaque, irregular protrusion and thrombus were 93.7%, 56.0%, 55.2%, and 33.4%, respectively. Minimal stent underexpansion defined by minimal stent area (MSA) &lt; 1.0 of reference area and severe stent underexpansion defined by MSA&lt; 0.8 of reference area were observed in 84.8% and 37.8% of stents. MACE occurred in 3.7% of cases at 1 year follow up. There was no death. AMI, stent thrombosis, and TLR occurred in 0.7%, 0.2%, and 3.2%. Univariate analysis showed small MSA (MSA&lt; 5 mm2) and irregular protrusion were correlated with MACE at 1year follow up (P=0.003 and P=0.044). Following adjustment of stent edge dissection, incomplete stent apposition, irregular protrusion, small MSA, stent type, and clinical presentations, small MSA and irregular protrusion remain as independent predictors of MACE (P=0.004 and P=0.037). Conclusions: OCT-detected stent complication rate is high. Small MSA and irregular protrusion are independent predictors of MACE at 1 year.
Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome
Authors: E Gluckman, MM Horowitz, RE Champlin, JM Hows, A Bacigalupo, JC Biggs, BM Camitta, RP Gale, EC Gordon-Smith, AM Marmont
Journal: Blood (1992)
Personal paper: Gene therapy for cancer managing expectations
Authors: A. A Melcher, I. Garcia-Ribas, R. G Vile
Journal: BMJ (1997)

Gene therapy seems to offer new hope in cancer treatment.The new molecular technology can be used to target tumour cells in many ways.These include techniques that correct genes directly-for example, by delivering a nucleic acid sequence that complements and therefore inactivates an oncogene (antisense technology) or by replacing copies of tumour suppressor genes that are often lost in malignant cells.However, the success of these direct approaches is limited because current technology cannot deliver therapeutic genes to all cancer cells.Alternative strategies have been developed using genes that encode proteins, such as cytokines, which can activate the patient's immune response against the tumour.Another application of gene therapy, which is already undergoing extensive clinical trials, is the transduction of tumour cells with so called suicide genes, which encode enzymes that can convert a prodrug to its toxic metabolite.Despite the diversity of gene therapies for cancer in both the laboratory and clinic, disappointment is emerging that gene therapy has not fulfilled its early promise. 1 Since no dramatic clinical success has been reported to date, this criticism cannot be ignored, and an objective reconsideration of the potential of gene therapy is timely.Gene therapy has failed to live up to expectations so far because these have been unrealistic.A lack of realism can be destructive if it leads to disillusionment.Potential benefits of a new approach may be lost if research is abandoned prematurely because dramatic advances have not been made.In oncology, the excitement engendered by gene therapy has been heightened by the inadequacy of current treatments for many of the common adult cancers.There are good scientific explanations for the inability of gene therapy to produce impressive cures in cancer, but for an understanding of these, gene therapy must be considered within the context and aims of current treatment strategies.Gene therapy provides a prime example of how the medical and scientific communities, working in isolation, can fail to make progress.Doctors may not understand the limitations of the new technology offered by scientists, and scientists may not understand where and how doctors want to apply gene therapy in cancer treatment.By combining scientific and medical approaches, we can define where and why gene therapy is likely to work or fail and explain why gene therapy must not be abandoned before it has had either the time or opportunity to show its worth.
THE MEDICAL ASPECTS OF NATIONAL HEALTH INSURANCE
Authors: Grant Fleming
Journal: Annals of Internal Medicine (1934)

Article1 August 1934THE MEDICAL ASPECTS OF NATIONAL HEALTH INSURANCEGRANT FLEMING, M.D.GRANT FLEMING, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-8-2-220 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNational Health Insurance is a very live topic today. What is more, it is a very serious thing for the medical profession at large, if not for the public. It is well that we should understand it properly, that we should have some conception of the forms it may take, and it is further important that we, as medical men, should be prepared to advise our governments and communities as to the manner in which it should be conducted—should it eventually come to pass as a government measure or as a service to the community.It has often been said... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Montreal, Canada*Delivered before the American College of Physicians, Chicago, Ill., April 18, 1934. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1934Volume 8, Issue 2Page: 220-228KeywordsHealth insurance ePublished: 1 December 2008 Issue Published: 1 August 1934 PDF downloadLoading ...