tbuckley/cabot-search huggingface dataset:
Abstract 2306: Pre-clinical development of 4′-thio-2′-deoxycytidine (TdCyd) as a DNA-demethylating agent for use in treating solid tissue tumors
Authors: Robert J. Kinders, Melinda Hollingshead, Jaideep Thottassery, William B. Parker, Thomas D. Pfister, Lawrence W. Anderson, Joseph E. Tomaszewski, Jerry M. Collins, James H. Doroshow
Journal: Cancer Research (2014)

Abstract Targeting cancer epigenetic control of cell growth via DNA methylation has been successful in treating hematologic diseases, such as Decitabine (DAC) and Azacitidine for Myelodysplastic Syndrome including Acute Myelomonocytic Leukemia. This success has not extended to solid tissue tumors. The Division of Cancer Treatment and Diagnositcs of NCI has initiated pre-clinical development of TdCyd as an agent for treating solid tumors after promising early results in a lung adenocarcinoma xenograft model (NCI-H23). IP dosing at 5MKG (0.56 MTD) in nu/nu mice on a Q5D x 3 cycle schedule resulted in tumor stasis with no accompanying weight loss in the mice. A DAC-treated control arm treated at MTD resulted in tumor growth delay but not stasis, and a 10% weight loss was noted. Intratumoral levels of DNMT1 were reduced to undetectable levels in xenografts post administration of TdCyd by ELISA and Western Blot assays, but were unaffected by DAC treatment. Mass Spectrometry analysis demonstrated incorporation of both TdCyd and thiothymidine (TdThd) into H23 DNA. In vitro experiments on a selected panel of cancer cell lines confirmed the conversion of TdCyd to the triphosphate and re-expression of tumor suppressor proteins p15 and p16. Funded by NCI Contract No. HHSN261200800001E. Citation Format: Robert J. Kinders, Melinda Hollingshead, Jaideep Thottassery, William B. Parker, Thomas D. Pfister, Lawrence W. Anderson, Joseph E. Tomaszewski, Jerry M. Collins, James H. Doroshow. Pre-clinical development of 4′-thio-2′-deoxycytidine (TdCyd) as a DNA-demethylating agent for use in treating solid tissue tumors. [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 2306. doi:10.1158/1538-7445.AM2014-2306
Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults
Authors: M. Alvarez, S. Monge, N. Chueca, V. Guillot, P. Viciana, L. Anta, C. Rodriguez, J.L. Gomez-Sirvent, G. Navarro, I. de los Santos, S. Moreno, F. García
Journal: Clinical Microbiology and Infection (2014)
Distinct Patterns of Dystrophin Organization in Myocyte Sarcolemma and Transverse Tubules of Normal and Diseased Human Myocardium
Authors: R. R. Kaprielian, S. Stevenson, S. M. Rothery, M. J. Cullen, N. J. Severs
Journal: Circulation (2000)

Background —Genetic mutations of dystrophin and associated glycoproteins underlie cell degeneration in several inherited cardiomyopathies, although the precise physiological role of these proteins remains under discussion. We studied the distribution of dystrophin in relation to the force-transducing vinculin-rich costameres in left ventricular cardiomyocytes from normal and failing human hearts to further elucidate the function of this protein complex. Methods and Results —Single- and double-label immunoconfocal microscopy and parallel high-resolution immunogold fracture-label electron microscopy were used to localize dystrophin and vinculin in human left ventricular myocytes from normal (n=6) and failing hearts (idiopathic dilated cardiomyopathy, n=7, or ischemic heart disease, n=5). In control cardiomyocytes, dystrophin had a continuous distribution at the peripheral sarcolemma, with concentrated bands corresponding to the vinculin-rich costameres. Intracellular labeling extended along transverse (T) tubule membranes. Fracture-label confirmed this distribution, showing significantly greater label on plasma membrane fractures overlying I-bands (I-band 4.1±0.3 gold particles/μm; A-band 3.3±0.2 gold particles/μm: mean±SE, P =0.02). Hypertrophied myocytes from failing hearts showed maintenance of this surface distribution except in degenerating cells; there was a clear increase in intracellular dystrophin label reflecting T-tubule hypertrophy. Conclusions —Dystrophin partially colocalizes with costameric vinculin in normal and hypertrophied myocytes, a distribution lost in degenerating cells. This suggests a primarily mechanical role for dystrophin in maintenance of cell membrane integrity in normal and hypertrophied myocytes. The presence of dystrophin in the cardiac T-tubule membrane, in contrast to its known absence in skeletal muscle T-tubules, implies additional roles for dystrophin in membrane domain organization.
IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS
Authors: Robert F. Parker, Thomas M. Rivers
Journal: The Journal of Experimental Medicine (1936)

Methods have been described by which the number of elementary bodies present in a suspension can be estimated. It has been shown that by means of replicate counts, in which the Petroff-Hausser chamber was used, a high degree of accuracy can be attained. By means of the Gates densitometer, the number of elementary bodies in a suspension can be determined with a coefficient of variation of about 3.0 per cent. A method has been described by which the accuracy of estimation of the infectious titer of a suspension can be increased without greatly enlarging the number of animals employed. This consists of selecting as the end-point that dilution of virus which on intradermal inoculation in a rabbit would lead theoretically to an equal number of positive and negative results. The statistical advantages of this method have been confirmed by the experiences of other laboratories. By the application of the methods described, there was shown to be a direct correlation between the number of elementary bodies and the number of infectious units of virus present in a given suspension. At the mean of the distribution this ratio is as the logarithms 9.62 to 8.0. To extrapolate this curve, in order to determine the number of elementary bodies present in a single infectious unit, while tempting, is probably not justifiable. It must likewise be remembered that the data given apply to a particular strain of vaccine virus, and that the number of infectious units has been determined by intradermal inoculation of rabbits. It appears also that this method may be of value in studies of the virulence of different strains of vaccine virus, since by its application one may determine not only the infectious liter of a suspension, but its content of elementary bodies. In the agglutination reaction it was found that optimum titers of serum were obtained when the test antigen contained from 2.0 x 10(9) to 1.05 x 10(10) elementary bodies per cc. Approximately 1.95 x 10(8) particles per cc. of suspension were required for the production of visible agglutination.
<i>Euphorbia peplus:</i>18th-Century Insights on a 21st-Century Therapy
Authors: Navya S. Nambudiri, Vinod E. Nambudiri
Journal: JAMA Dermatology (2013)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells
Authors: Frank Kaiser, Dorthe Cook, Stamatia Papoutsopoulou, Ricardo Rajsbaum, Xuemei Wu, Huei-Ting Yang, Susan Grant, Paola Ricciardi-Castagnoli, Philip N. Tsichlis, Steven C. Ley, Anne O'Garra
Journal: The Journal of Experimental Medicine (2009)

Stimulation of Toll-like receptors (TLRs) on macrophages and dendritic cells (DCs) by pathogen-derived products induces the production of cytokines, which play an important role in immune responses. Here, we investigated the role of the TPL-2 signaling pathway in TLR induction of interferon-β (IFN-β) and interleukin-10 (IL-10) in these cell types. It has previously been suggested that IFN-β and IL-10 are coordinately regulated after TLR stimulation. However, in the absence of TPL-2 signaling, lipopolysaccharide (TLR4) and CpG (TLR9) stimulation resulted in increased production of IFN-β while decreasing IL-10 production by both macrophages and myeloid DCs. In contrast, CpG induction of both IFN-α and IFN-β by plasmacytoid DCs was decreased in the absence of TPL-2, although extracellular signal-regulated kinase (ERK) activation was blocked. Extracellular signal-related kinase–dependent negative regulation of IFN-β in macrophages was IL-10–independent, required protein synthesis, and was recapitulated in TPL-2–deficient myeloid DCs by retroviral transduction of the ERK-dependent transcription factor c-fos.
Reviews and Notes: Cardiology: Calcium Antagonists in Clinical Medicine
Authors: Mihai Gheorghiade
Journal: Annals of Internal Medicine (1993)

Literature of Medicine1 September 1993Reviews and Notes: Cardiology: Calcium Antagonists in Clinical MedicineMihai Gheorghiade, MDMihai Gheorghiade, MDNorthwestern University, Chicago, IL 60611.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-5-199309010-00047 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Cardiology: Calcium Antagonists in Clinical MedicineMurray Epstein. 438 pages. Philadelphia: Hanley & Belfus; 1992. $55.00.Although several proceedings of symposia on calcium channel blockers have been published, there has been no recent textbook on the clinical aspects of calcium channel blocker therapy in clinical medicine. This 20-chapter book fills that gap. The book reviews in detail the biochemical and pharmacokinetics of calcium channel blockers and their clinical role in the therapy of hypertension, heart failure, myocardial infarction, arrhythmias, gastrointestinal pathology, pulmonary disorders, and cerebrovascular insufficiency. The book also addresses the effects of calcium antagonists on the kidney and renal protection, including ... Author, Article, and Disclosure InformationAffiliations: Northwestern University, Chicago, IL 60611. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1993Volume 119, Issue 5Page: 444KeywordsCalciumCalcium antagonist therapyCalcium channel blockerHeart failureHypertensionMyocardial infarctionPharmacokineticsPulmonary hypertensionRenal transplantationUnstable angina ePublished: 15 August 2000 Issue Published: 1 September 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Upregulation of the SOX5 by promoter swapping with the P2RY8 gene in primary splenic follicular lymphoma
Authors: C T Storlazzi, F Albano, C Lo Cunsolo, C Doglioni, M C Guastadisegni, L Impera, A Lonoce, S Funes, E Macrì, P Iuzzolino, I Panagopoulos, G Specchia, M Rocchi
Journal: Leukemia (2007)
Potentiometric Measurement of Glucose Concentration with an Immobilized Glucose Oxidase/Catalase Electrode
Authors: Lemuel B Wingard, Chung C Liu, Sidney K Wolfson, Shang J Yao, Allan L Drash
Journal: Diabetes Care (1982)

A series of enzyme electrodes for measurement of glucose have been constructed. The electrodes contain glucose oxidase immobilized on platinum, either with or without co-immobilization of catalase. When placed in buffered glucose, the enzyme electrodes show a potentiometric response to glucose with respect to a Ag/AgCl reference electrode. This response is reproducible in the physiologic range of glucose concentrations. The immobilization technique, some of the environmental variables such as oxygen concentration and pH, and several compounds that might interfere with the selectivity of the enzyme electrodes for glucose have received preliminary study. This direct potentiometric approach is undergoing further evaluation to determine the basic electrochemical mechanism responsible for the potentiometric signal and whether it can be adapted for continuous in vivo monitoring of the glucose concentration in body fluids.
Where are we now with vaccines against AIDS?
Authors: G C Schild, E J Stott
Journal: BMJ (1993)

Extensive studies in experimental animal models and phase I and II clinical trials in humans provide some grounds for optimism about developing a vaccine for AIDS. Over 200 monkeys have been protected by simple inactivated vaccines against infection with a lethal challenge dose of simian immunodeficiency virus (SIV). Passive transfer of the antibody to SIV has been shown to prevent infection. Recent vaccination with attenuated, live SIV protected against a challenge with 1000 monkey infectious doses of virus. Studies in chimpanzees have been limited to the unrepresentative IIIB strain of HIV-1. Purified recombinant envelope protein either as the gp 120 surface unit or as the entire gp 160 protein has protected a proportion of chimpanzees against infection. Several experimental immunogens have been tested in phase I and II clinical trials in human volunteers. 5 different recombinant HIV envelope subunits, live recombinant vaccinia virus expressing HIV envelope, and synthetic peptides or virus-like particles derived from yeast, but expressing HIV core proteins, have been used for vaccines that have proved safe. However, large quantities of the subunit HIV antigens are required, and the humoral immune responses are short-lived. Trials with the live recombinant vaccinia virus expressing HIV envelope represent the first use of live recombinant virus in humans. Further studies are under way in France with an avian poxvirus vector, which is host restricted and therefore potentially safer. STudies with combinations of live recombinant virus vaccines followed by immunization with purified subunits indicate that this approach may stimulate both cellular immunity and neutralizing antibodies at higher concentrations than previously observed. The WHO has identified sites in Brazil, Rwanda, Thailand, and Uganda for large scale trials of the efficacy of AIDS vaccines that will probably begin within 5 years.
Anaphylactoid Shock Due to Penicillin
Authors: B. Ashworth
Journal: BMJ (1965)

BRIT reaction to oral phenoxymethylpenicillin in 1957.1Regarding treatment of any anaphylactoid reaction, I am sure prompt recognition is vital, and I am equally sure that prompt administration of adrenaline is the correct initial course because it is effective, acts quickly, and every doctor carries it in his bag.-Iam, etc., Leeds 17.
Tooth and nail
Authors: Fiona Godlee
Journal: BMJ (2007)

If you're interested in what BMJ editors do when they are out and about, there's a new blog on bmj.com (http://blogs.bmj.com/bmj/category/comment/editors-at-large). It gives a flavour of some of the conferences we've been at and some of the people we've met: the eponymous Dr Kawasaki for one, UK public health grandee Rod Griffiths for another. I met Rod at a conference in Athens and we got talking about fluoride. No one in their right mind would get involved in the debate about water fluoridation, he said. It's a minefield. But this week we do get involved, and against his better judgment, so …
Acute and long-term results of radiofrequency ablation of common atrial flutter and the influence of the right atrial isthmus ablation on the occurrence of atrial fibrillation
Authors: Sebastian Schmieder, Gjin Ndrepepa, Jun Dong, Bernhard Zrenner, Juergen Schreieck, Michael A. Schneider, Ildiko Dobran, Martin R. Karch, Claus Schmitt
Journal: Journal of the American College of Cardiology (2003)
Biostatistics: An Introductory Text
Authors: Lester S. King
Journal: JAMA (1964)

All too rarely does an author have clearly in mind the specific audience for whom he is writing, a precise formulation of what he is trying to convey, and at the same time substantial expository skill. Dr. Goldstein, however, with this new text, should be welcomed into that select group of authors. The present volume had its inception when the author began to teach principles of biostatistics to pharmacology students. With prolonged experience he has evolved a text which tries to provide an understanding of statistical principles as applied to biology. Dr. Goldstein does not try to give a "systematic mastery of its mathematical basis." Instead, he proceeds on the view that the student "must be shown when, where, and how the tools can best be used, and in a general way why they work. He does not have to know how the tools were fashioned, nor even the proofs
Comparison of Myocardial Perfusion Reserve Before and After Coronary Balloon Predilatation and After Stent Implantation in Patients With Postangioplasty Restenosis
Authors: Michael Haude, Guido Caspari, Dietrich Baumgart, Ru¨diger Brennecke, Ju¨rgen Meyer, Raimund Erbel
Journal: Circulation (1996)

Background Stents provide a scaffold for coronary arteries after angioplasty and inhibit elastic recoil. Methods and Results In 25 patients with postangioplasty restenosis of the left anterior descending artery, ECG-gated digital subtraction coronary angiograms were recorded at baseline and during hyperemia (12 mg papaverine IC) before and after balloon predilatation (PTCA), after implantation of a Palmaz-Schatz stent, and after 6 months. Densitometric evaluation revealed different time and density parameters to calculate two definitions of myocardial perfusion reserve (MPR1 and MPR2) and maximum flow ratio (MaxFR). Poststenotic MPR1 increased from 1.57±0.14 to 2.59±0.86 after PTCA and to 3.10±0.41 after stenting, with 2.90±0.65 at follow-up (ANOVA, P &lt;.05), while reference MPR1 remained unchanged at 3.10±0.40. Poststenotic MPR2 increased from 1.36±0.28 to 2.50±1.20 and to 3.40±0.58, respectively, with 3.20±0.92 at follow-up (ANOVA, P &lt;.05), while reference MPR2 remained unchanged at 3.40±0.60. MaxFR was 2.13±0.53 after PTCA, 2.83±0.35 after stenting, and 2.73±0.58 at follow-up (ANOVA, P &lt;.05). A good correlation was found between minimal stenotic luminal diameter and MPR1 or MPR2 ( r =.87 and r =.94) and between luminal gain and MaxFR ( r =.75). A negative correlation was measured between recoil and MPR1, MPR2, and MaxFR ( r =−.80, r =−.86, and r =−.83). At follow-up, a steeper correlation was found between MPR and minimal stenosis diameter (MPR1: slope, 0.52 versus 0.91; MPR2: slope, 1.48 versus 1.95) and between MaxFR and net lumen gain (slope, 0.78 versus 1.27). Conclusions Coronary stent implantation in patients with postangioplasty restenosis normalized poststenotic myocardial perfusion immediately as a result of a larger postprocedural lumen and a more pronounced inhibition of elastic recoil. After 6 months this benefit was sustained despite progressive lumen loss.
Guidelines for clinical guidelines
Authors: R. Jackson, G. Feder
Journal: BMJ (1998)

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions about appropriate health care for specific circumstances.1 Clinicians are being inundated by a tidal wave of guidelines. In Britain alone, regional programmes for audit have recently developed about 2000 guidelines or protocols.2 In addition to numerous clinical guidelines, a number of “guidelines for guidelines” have been produced, ranging from simple3 to complex.4 These reflect the increasing attention being paid to the methodology of guidelines development and the validity of guideline recommendations. While we support the increasingly rigorous approach taken to guideline development, it is important to re-emphasise the central role of guidelines themselves, which is to help clinicians make better decisions.

Clinicians need simple, patient specific, user friendly guidelines. We highlight three key components for such guidelines. The first is the explicit identification of the major decisions, relevant to patients, which have to be made, and the possible consequences of these decisions. Many encounters with patients involve multiple decisions, so the key to developing usable guidelines is to identify …
Stimulated Renin: A Screening Test for Hypertension
Authors: LAWRENCE WALLACH
Journal: Annals of Internal Medicine (1975)

The usefulness of the furosemide screening test in ambulant hypertensive patients was prospectively studied. Outpatients were given 60 mg of furosemide by mouth, and 5 hours later plasma renin activity was measured. Subsequent investigation in hospital showed that the patients fell into four groups: extreme hyporeninemia (primary aldosteronoma), suppressed renin (confirmed suppressed-renin hypertension), normal renin (essential hypertension), and elevated renin (renovascular hypertension). The plasma renin activity measured by the test correlated well with standardized in-hospital measurement. This test identifies patients who may have primary aldosteronism, suppressed-renin hypertension, or renovascular disease as the cause of hypertension, thus indicating those requiring further in-hospital investigation. More significantly, it identifies those not requiring further study, thus decreasing hospitalization. Finally, it helps in the selection of specific antihypertensive therapy based on plasma renin activity.
Abstract B11: EGFR polymorphism as a predictor of clinical outcome in advanced lung cancer patients treated with EGFR-TKI
Authors: Minkyu Jung, Chul Ho Lee, Hyung Soon Park, Ji Hyun Lee, Joo Hang Kim, Young Ae Kang, Se Kyu Kim, Joon Chang, Dae Jun Kim, Byoung Chul Cho
Journal: Clinical Cancer Research (2012)

Abstract Background: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of efficacy for EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcome in NSCLC patients treated with EGFR-TKI. Methods: A polymorphic dinucleotide repeat (CA simple sequence repeat 1 [CA-SSR1]) in intron one and single nucleotide polymorphisms in the promoter region (SNP -216 GG or GT) were evaluated in 71 NSCLC patients by PCR-RFLP and DNA sequencing. Genetic polymorphisms were correlated with clinical outcomes of EGFR-TKIs. Results: SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T was significantly higher than that for the GG (62.5% vs. 27.4%, P=0.044). SNP-216G/T genotype was also associated with longer progression-free survival compared with GG genotype (16.7 months vs. 5.1 months, P=0.005). However, Genotypes for the CA-SSR1 was not associated with the efficacy of EGFR-TKI. Conclusions: SNP-216G/T polymorphism is potential predictor for clinical outcome in NSCLC patients treated with EGFR-TKI.
Photodynamic Therapy with Verteporfin for Symptomatic Circumscribed Choroidal Hemangioma: Five-Year Outcomes
Authors: Maria Antonietta Blasi, Alessandra C. Tiberti, Andrea Scupola, Angelo Balestrazzi, Egle Colangelo, Paola Valente, Emilio Balestrazzi
Journal: Ophthalmology (2010)