tbuckley/cabot-search huggingface dataset:
Abstract 1958: Interrogating hedgehog pathway and smoothened inhibition by PF-04449913 in patient-derived acute myeloid leukemia models
Authors: Amy Jackson-Fisher, Pamela Whalen, Mark Elliott, Melissa McMahon, Enhong Chen, Xianxian Zheng, Mark Ozeck, Donghui Huang, Paul Lira, Joseph Lee, Cathy Zhang, Justine Lam, Mary Spilker, Shibing Deng, Patrick Lappin, Penny Venne, Cynthia Heinlein, Annelie Schairer, Karen McLachlan, Todd VanArsdale
Journal: Cancer Research (2014)

Abstract Aberrant activation of the Hedgehog (Hh) signaling pathway has been implicated in a variety of cancers and a small molecule inhibitor of Smoothened (SMO), Vismodegib, has been approved for the treatment of basal cell carcinoma, a disease frequently driven by Hh pathway signaling due to pathway mutations. SMO dependent Hh signaling has also been implicated in models of myeloid leukemia, primarily CML, where genetic loss of SMO or pharmacological inhibition limits disease progression in part through targeting the leukemic stem cell (LSC). Outside of BCR-ABL driven leukemia the role of Hh signaling and impact of SMO inhibition on disease progression and the LSC remains unclear. To explore the role of Hedgehog pathway signaling and interrogate responses to SMO inhibition in AML, a panel of primary AML patient-derived models was utilized to examine responses to PF-04449913, an oral small molecule SMO inhibitor currently in early phase clinical trials targeting myeloid malignancies. AML patient samples were characterized for Hh pathway expression levels and screened for responses to PF-04449913. Ex vivo treatment of AML bone marrow cells showed PF-04449913 was capable of inhibiting Hh pathway activity, reducing expression of key LSC regulators and decreasing populations of cells expressing LSC markers. Use of AML xenotransplant models to assess in vivo responses to PF-04449913 as single agent and in combination with Cytarabine have shown potential for combination efficacy of the two agents in select models suggesting patient selection strategies may be critical for SMO inhibitor-based therapies in AML. Citation Format: Amy Jackson-Fisher, Pamela Whalen, Mark Elliott, Melissa McMahon, Enhong Chen, Xianxian Zheng, Mark Ozeck, Donghui Huang, Paul Lira, Joseph Lee, Cathy Zhang, Justine Lam, Mary Spilker, Shibing Deng, Patrick Lappin, Penny Venne, Cynthia Heinlein, Annelie Schairer, Karen McLachlan, Todd VanArsdale. Interrogating hedgehog pathway and smoothened inhibition by PF-04449913 in patient-derived acute myeloid leukemia models. [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 1958. doi:10.1158/1538-7445.AM2014-1958
Masking, Blinding, and Peer Review
Authors: Frank Davidoff
Journal: Annals of Internal Medicine (1998)

Letters15 July 1998Masking, Blinding, and Peer ReviewFrank Davidoff, MD, EditorFrank Davidoff, MD, EditorEditor.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-2-199807150-00036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. McDuffie's description of his experience as reviewer and editor adds usefully to the debate on the evolving issue of blinding in peer review. There is little doubt that reviewers contribute substantially to the intellectual work of published studies and that, for the most part, their work remains “unhonored and unsung.” My predecessors in the editorship of Annals, Robert and Suzanne Fletcher, began the important tradition of writing personal letters of thanks to the 30% of reviewers each year whose reviews were top rated by our associate editors. We have continued this tradition, and every year we receive ... Author, Article, and Disclosure InformationAuthors: Frank Davidoff, MD, EditorAffiliations: Editor. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1998Volume 129, Issue 2Page: 165KeywordsPeer review ePublished: 15 August 2000 Issue Published: 15 July 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Phase I Study of Radical Thoracic Radiation, Weekly Irinotecan, and Cisplatin in Locally Advanced Non-small Cell Lung Carcinoma
Authors: Corey J. Langer, Robert Somer, Samuel Litwin, Steven Feigenberg, Benjamin Movsas, Christine Maiale, Eric Sherman, Michael Millenson, Nicos Nicoloau, Chao Huang, Joseph Treat
Journal: Journal of Thoracic Oncology (2007)
Doxorubicin toxicity. Onycholysis, plantar callus formation, and epidermolysis
Authors: F. B. Manalo
Journal: JAMA (1975)

DOXORUBICIN is now a well-established anticancer agent with significant activity against a large variety of solid tumors and hematologic malignancies. Its pharmacology is well described in two recent reviews.1,2The known toxic reactions are bone marrow suppression, stomatitis, alopecia, cardiotoxicity, and, more recently, melanotic changes in the palms, soles, and nail beds.3,4We report a case of dermatologic toxic reactions not previously described, to our knowledge.  Report of a Case  A 41-year-old white man was admitted on Aug 8,1974, because of soreness in both hands and feet, with loosening of all finger and toe nails (Figure). In July 1973, the patient underwent a shoulder disarticulation for fibrosarcoma of the right humerus. Postoperatively, he received 4,000 rads in combination with systemically given dactinomycin over a period of five weeks, with no toxic reactions. He was disease-free over the subsequent seven months, after which bilateral pulmonary metastases were detected on
A defect in the regulation of major histocompatibility complex class II gene expression in human HLA-DR negative lymphocytes from patients with combined immunodeficiency syndrome.
Authors: B Lisowska-Grospierre, D J Charron, C de Préval, A Durandy, C Griscelli, B Mach
Journal: Journal of Clinical Investigation (1985)

Patients with an autosomal recessive combined immunodeficiency are characterized by an HLA negative phenotype of activated T and B lymphocytes. To determine the molecular basis of this syndrome we have studied the biosynthesis of class I and II antigens and the expression of relevant genes in these patients. The synthesis of the HLA A, B, and C heavy chain is markedly decreased, while beta 2 microglobulin is made in normal amounts. Biosynthesis of HLA-DR alpha-chain and beta-chain is abolished in the lymphocytes of these patients and there is a total absence of mRNA for either alpha-chains or beta-chains of HLA-DR. This indicates that the lack of class II antigen on these lymphocytes results from a block in the expression of HLA-DR genes. The Ii-chain, the invariant polypeptide associated intracellularly with HLA-DR, and its mRNA are made in normal amounts. Since the structural genes coding for class II polypeptides do not seem to be affected, the reported genetic defect in the patients concerns the regulation of the expression of HLA-DR genes.
Abstract 745: Role of G-quadruplex structures in the human RET promoter region in the regulation of this gene.
Authors: Daekyu Sun, Yoon-Joo Shin
Journal: Cancer Research (2013)

Abstract The medullary thyroid carcinoma (MTC) is a tumor type characterized by germline point mutations of the RET (REarranged during Transfection) proto-oncogene. Since these mutations are known to induce oncogenic activation of RET tyrosine kinase, various therapeutic strategies interfering with the oncogenic function of RET protein have been developed and tested for treating RET-associated cancers in several preclinical and clinical studies. Our previous study has demonstrated that the G-rich strand in the polypurine/polypyrimidine (pPu/pPy) region of the RET proximal promoter is capable of forming intramolecular G-quadruplex structures in vitro in the presence of K+, which can be further stabilized by a G-quadruplex interactive agents. Thus, the detailed mechanism by which G-quadruplex structures regulate RET transcription has been studied using mutation analysis and promoter reporter assays together with a detailed analysis of transcription factor binding to the RET promoter in vivo. To this end, we have explored the Flp-In cell system using homologous recombination, which allows integration of a single copy of a wild type or G-quadruplex-mutant RET promoter–luciferase construct into a specific genomic recombination locus (FRT site) in a host Flp-In the human embryonic kidney 293 (HEK293) cell line. Thus, differences in reporter expression levels from isolated isogenic cell clones can be ascribed more confidently to promoter-specific effects, rather than enhancer/silencer artifacts due to variations in integration sites. Using these isogenic cell lines, we are able to provide strong evidence for G-quadruplex-dependent transcriptional repression of the RET gene in vivo. Citation Format: Daekyu Sun, Yoon-Joo Shin. Role of G-quadruplex structures in the human RET promoter region in the regulation of this gene. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 745. doi:10.1158/1538-7445.AM2013-745
Achieving "Physiological Gastrectomy" by Gastric Freezing
Authors: Owen H. Wangensteen
Journal: JAMA (1962)

Short periods of gastric freezing are well tolerated by dog and man. Results in both canine and human subjects, with the inflowing coolant at temperatures of —17° to —20° C. (1.4° to —4.0° F.), have been very satisfying. Isolated gastric pouches, whether Pavlov, Heidenhain, or antral, when frozen for an hour, become unresponsive to physiological stimuli. Gastric freezing is followed by alterations in the secretory responses of the stomach which justify the description "physiological gastrectomy." The stomachs of 24 patients having duodenal ulcer have been frozen with subjective relief of symptoms, disappearance of duodenal ulcer craters, and significant decreases in gastric secretory responses.
Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial sarcoma: a study of the French Sarcoma Group
Authors: A. Italiano, N. Penel, Y.-M. Robin, B. Bui, A. Le Cesne, S. Piperno-Neumann, M. Tubiana-Hulin, E. Bompas, C. Chevreau, N. Isambert, S. Leyvraz, P.P. du Chatelard, A. Thyss, J.-M. Coindre, J.-Y. Blay
Journal: Annals of Oncology (2008)
Recognition of unwanted drug effects.
Authors: R. Doll
Journal: BMJ (1969)

The system of detection of unwanted side effects in new drugs distributed to the general public is described with several specific drugs cited including reference to the effects of oral contraceptives (OCs) and the manner in which their  connection to thromboembolic phenomena was established.  Attempts to estimate the incidence of thromboembolism by women using OCs from reports to the Committee on Safety of Drugs proved unsatisfactory.  3 separate studies however were found to give evidence in support of the relationship.  1 study interviewed young women recorded in the diagnostic index as having attended for a new episode of vascular pulmonary embolism or venous cerebral or coronary thrombosis of women who had no predisposing cause for the disease.  In the 3rd study prepared for the Committee on Safety of Drugs all the deaths that had occurred in England Wales and Northern Ireland during 1966 in women 20-44 years old in which thrombosis or embolism of the pulmonary cerebral or  coronary vessels was referred to on the death certificate were enumerated.  The results showed the risks of developing deep vein thrombosis pulmonary embolism or cerebral thrombosis in the OC user 8 times that of the nonuser and the risks of developing phlebitis 3 times as great in the OC user.  Pharmacological experience and knowledge of the mechanisms by which drugs act should enable many effects to be predicted.  A system of medical intelligence such as mortality statistics can provide information on trends.  It is suggested that a system of record linkage by computer is needed and that early warning system of the effect of new drugs should be limited to unusual or severe effects.  Another suggestion encompasses use of the practitioners prescription as a method of monitoring the patients at risk from a new drug.
The limited list: the patients' views.
Authors: R G Neville, D E Meekison
Journal: BMJ (1985)

Two months after the introduction of the limited list eight general practitioners and six pharmacists in the Tayside region were asked about their patients' views on the introduction. Two general practitioners said that they had had virtually no problems or complaints, and another general practitioner said that six of 300 prescriptions had presented problems. The few problems that were reported by general practitioners and pharmacists had occurred mostly among the elderly, and a classification is given of the sorts of problems.
Postcricoid dysphagia and iron deficiency in men.
Authors: M. Chisholm, R. Wright
Journal: BMJ (1967)

The drawbacks are the absence of stitchable material in some cases, intolerance of catgut in others.Furthermore, plastic repairs are elaborate exhaustive affairs for the elderly, and not always tolerant of subsequent labours in the younger women.It seems probable that there is a large field among the prolapses for permanent implants as substitutes for the normal supports when these have been damaged.These implants will be of synthetic material that is non-irritant, and they will be placed with increasing accuracy in positions which closely resemble those of the natural supports.Their insertion will demand new techniques of combined abdominoperineal approach, but as little or no tissue excision is required there will be less bleeding, less morbidity, and early ambulation.Procidentia in an old woman was successfully corrected by a sling of polyethylene which raised the cervix by anchorage to the inguinal canals.The technique of inserting the sling extraperitoneally with the aid of a metal bougie is described.It is suggested that there is a case for using non-absorbable, non- irritant materials in treating prolapse without excising tissue.Combined abdominoperineal techniques and substitution for damaged anatomical structures are foreseen.
Comment on: Tsiakou et al. Arterial Stiffness Is Inversely Related to Plasma Adiponectin Levels in Young Normotensive Patients With Type 1 Diabetes. Diabetes Care 2013;36:734–736
Authors: Hidetaka Hamasaki, Hidekatsu Yanai
Journal: Diabetes Care (2013)

We read the article by Tsiakou et al. (1) with great interest. This study showed a negative association between plasma adiponectin concentrations and arterial stiffness in young type 1 diabetic patients without complications. However, we recently showed a positive association between plasma adiponectin concentrations and arterial stiffness in patients with type 2 diabetes (2). Adiponectin has anti-inflammatory and anti-atherosclerotic effects, and reduction of plasma adiponectin has been reported to contribute to …
Teaching medical students in general practice: respecting patients' rights
Authors: C. Williamson, P. Wilkie
Journal: BMJ (1997)

As health systems put more emphasis on primary care, it follows that primary care settings will increasingly be used for teaching medical students. The study this week by Flynn et al on patients' views about having a medial student present during consultations in general practice confirmed the usual finding that patients are happy to help medical education in this way (p 1142).1 But patients were not always happy about how the student's presence and involvement were presented. In particular some were concerned about informed consent and confidentiality—the same issues that trouble patients in treatment and research.2 3 Changing practice to allay these concerns is important if controversy and distrust are to be avoided—and should also benefit patients and students in other ways.

Patients have the right to choose whether to participate in the training of medical students.4 But in many cases in this study patients' …
Cholestasis and Rubeola
Authors: G. Pelletier, C. Buffet, K. Turner, P. Attali, J. P. Etienne
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The article by McLellan and Gleiner inThe Journal(1982; 247:2000) has led us to report the following case. <h3>Report of a Case.—</h3> On June 20, 1982, a 19-year-old man had a conjunctivitis, followed eight days later by a temperature of about 39 °C to 40 °C, muscular pains, and a rash with nonconfluent and nonitchy macules. Tonsillitis, cervical lymph nodes, and a discrete meningitislike syndrome were found. The patient received penicillin G intramuscularly for five days and acetaminophen, 660 mg/day, for three days. Fever and rash disappeared in three days. On July 6, jaundice with itching appeared. Physical examination results were normal. Biologic results are given in the Table. The jaundice increased. Echotomography showed a homogenous liver, thin biliary ducts, and normal gallbladder. Endoscopic retrograde cholangiography showed normal biliary ducts and a normal Wirsungcanal. Serum hepatitis B virus markers and IgM antibodies to hepatitis A
Comparative Merits of Sodium and Procaine Penicillin
Authors: E. Griffiths, P. F. Jones, R. A. Shooter, J. A. Heady
Journal: BMJ (1949)

Bartholomew's Hospital Penicillin is widely used in general practice and in the out- patient departments of hospitals for the treatment of acute staphylococcal infections of the skin and subcutaneous tissues, but as yet the dosage employed in different hospitals varies widely.
US Requires Coverage for Contraceptives, Other Women's Preventive Health Services
Authors: B. M. Kuehn
Journal: JAMA (2011)

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 Journals 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
Intrapericardial Interatrial Teratoma (Bronchogenic Cyst)
Authors: C. Harwell Dabbs, E. Converse Peirce, Freeman L. Rawson
Journal: New England Journal of Medicine (1957)

PRIMARY cardiac neoplasm is rare. With the frontiers of cardiac surgery advancing at the present rapid rate, there is a need for greater awareness of this possibility. There is also a need for exact anatomic diagnosis wherever possible so that the surgical attack can be planned wisely. Fortunately, this is possible with the specialized diagnostic aids available today.As recently as 1951, Prichard,1 in his excellent review of tumors of the heart, made the following comment:... tumors of the heart are rarely diagnosed before autopsy, largely because there is little knowledge of their natural history. Surgical treatment of these . . .
Magnitude of benefit from earlier thrombolytic treatment in acute myocardial infarction: new evidence from Grampian region early anistreplase trial (GREAT)
Authors: J. Rawles
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To generalise from the results of the Grampian region early anistreplase trial (GREAT) and to express the benefit of earlier thrombolysis in terms of lives saved per hour of earlier treatment. <b>Design</b>: Multivariate analysis of a randomised double blind trial. <b>Setting</b>: 29 rural practices in Grampian region and teaching hospitals in Aberdeen. <b>Subjects</b>: 311 patients with suspected acute myocardial infarction and without contraindications to thrombolysis who were seen by their general practitioners within four hours of the start of symptoms. <b>Interventions</b>: Anistreplase 30 units given intravenously, either by general practitioners before hospitalisation or later in hospital. <b>Main outcome measure</b>: Death within 30 months of entry into trial. <b>Results</b>: Death within 30 months was positively related to age (P&lt;0.0001) and to delay between start of symptoms and thrombolytic treatment (P=0.0004). However, the probability of dying rose exponentially with earlier presentation, so death within 30 months was negatively related to the logarithm of the time of randomisation (P=0.0163). In patients presenting two hours after start of symptoms each hour9s delay in receiving thrombolysis led to the loss of 21 lives per 1000 within 30 days (95% confidence interval 1 to 94 lives per 1000) (P=0.03) and 69 lives per 1000 within 30 months (16 to 141 lives per 1000) (P=0.0004). <b>Conclusions</b>: The magnitude of the benefit from earlier thrombolysis is such that giving thrombolytic treatment to patients with acute myocardial infarction should be accorded the same degree of urgency as the treatment of cardiac arrest. <h3>Key messages</h3> Key messages However, studies comparing treatment in the community with later treatment in hospital showed that earlier treatment did not significantly reduce mortality in the following month Continued follow up of Grampian region early anistreplase trial showed that mortality benefit of prehospital thrombolysis trebled between 30 days and 30 months after entry into trial Patients who sought medical help quickly after start of symptoms had more severe infarction, and thus a higher mortality risk, than those seeking help later, which can mask greater efficacy of earlier thrombolysis Giving thrombolytic treatment at the first opportunity should be considered as urgent as treatment of cardiac arrest
Neutralization of murine myeloid-derived suppressor cells enhances the efficacy of a chimeric antigen receptor T-cells directed against pediatric solid tumors
Authors: Steven L Highfill, Adrienne H Long, Rimas J Orentas, Crystal L Mackall
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Genetically engineered T-cells that express chimeric antigen receptors (CARs) to directly target tumor-expressed antigens have shown remarkable activity in clinical trials for hematologic malignancies, but remain unproven for the treatment of solid tumors. We find that in addition
TCT-898 Incidence and Impact of Acquired Thrombocytopenia on Bleeding Events and Mortality after Transcatheter Aortic Valve Replacement (TAVR)
Authors: Philippe Genereux, Susheel Kodali, Martin Leon, Philip Green, Benoit Daneault, Jean-Michel Paradis, Isaac George, Ajay Kirtane, Rebecca Hahn, Craig Smith, Mathew Williams
Journal: Journal of the American College of Cardiology (2012)
Human papillomavirus genotypes in rural Mozambique
Authors: Xavier Castellsagué, Clara Menéndez, Maria-Paz Loscertales, Janet R Kornegay, Francisco dos Santos, F Xavier Gómez-Olivé, Belen Lloveras, Nayana Abarca, Neide Vaz, Avertino Barreto, F Xavier Bosch, Pedro Alonso
Journal: The Lancet (2001)