tbuckley/cabot-search huggingface dataset:
Radiation induced molecular modulations in human breast adenocarcinoma cells after single (10Gy) and fractionated (2Gy x 5) dose irradiation.
Authors: R Madhusoodhanan, HS Terence, N Aravindan
Journal: Cancer Research (2009)

Abstract Abstract #5133 Background: Radiotherapy a recognized treatment modality for breast cancer patients is now considered mandatory for most patients undergoing conservative surgery and is considered appropriate for women at high risk of recurrence after mastectomy. However, relapse due to radio-resistance of cancer cells significantly affects the success of radiotherapy and cancer patient survival. Ascertaining the fractionated irradiation (FIR) modulated molecular targets is important to make tumors more susceptible to molecular targeted therapy. Accordingly, we investigated the (i) expression of 84 genes representing 6 functional pathways including Cell cycle and DNA damage repair, Apoptosis and cell senescence, Signal transduction and transcription, Adhesion, Invasion and metastasis and Angiogenesis; (ii) nuclear translocation and DNA-binding activity of NFκB and; (iii) expression of radio-responsive TNFα, IL-1α, pAKT, cIAP1, cIAP2 and survivin molecules after single dose (SDR) radiation and FIR protocols in human breast adenocarcinoma cells.&amp;#x2028; Methods: MCF-7 cells exposed to either SDR (10Gy) or FIR (2Gy x 5 days) and harvested after 24h were analyzed for alterations in gene expression using real-time Q-PCR-profiling. NFκB-DNA binding activity was analyzed using electrophoretic mobility shift assay and pIκB levels was measured using immunoblotting. Relative changes in the expression patterns of TNFα, IL-1α, pAKT, cIAP1, cIAP2 and survivin were determined using Q-PCR analysis and immunoblotting.&amp;#x2028; Results: Compared to the SDR, FIR treated cells showed an induced expression 61 (Cell cycle &amp; DNA damage repair - 12, Apoptosis &amp; cell senescence - 10, Signal transduction &amp; transcription - 7, Adhesion - 8, Invasion &amp; metastasis – 11 and Angiogenesis – 13) genes. Furthermore, we observed a relatively induced DNA binding activity of NFκB and phosphorylation of IκBα after FIR. Like-wise, we observed an induced expression of TNFα, IL-1α, pAKT, cIAP1, cIAP2 and survivin mRNA in cells exposed to FIR. The changes in these genes were confirmed at the protein level.&amp;#x2028; Discussion: These results along with the differential gene expression pattern support our hypothesis that FIR can induce molecular targets. In this initial analysis, NFκB and known NFκB regulated radio-responsive genes were found to be modulated. Currently, we are in the process of identifying similar FIR-induced targets and evaluate their potential for selective drug-targeted manipulation. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5133.
Brain metabolism of13N-ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography
Authors: Susanne Keiding, Michael Sørensen, Dirk Bender, Ole Lajord Munk, Peter Ott, Hendrik Vilstrup
Journal: Hepatology (2005)

Animal studies and results from 13N-ammonia positron emission tomography (PET) in patients with cirrhosis and minimal hepatic encephalopathy suggest that a disturbed brain ammonia metabolism plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE). We studied brain ammonia kinetics in 8 patients with cirrhosis with an acute episode of clinically overt HE (I-IV), 7 patients with cirrhosis without HE, and 5 healthy subjects, using contemporary dynamic 13N-ammonia PET. Time courses were obtained of 13N-concentrations in cerebral cortex, basal ganglia, and cerebellum (PET-scans) as well as arterial 13N-ammonia, 13N-urea, and 13N-glutamine concentrations (blood samples) after 13N-ammonia injection. Regional 13N-ammonia kinetics was calculated by non-linear fitting of a physiological model of brain ammonia metabolism to the data. Mean permeability–surface area product of 13N-ammonia transfer across blood–brain barrier in cortex, PSBBB, was 0.21 mL blood/min/mL tissue in patients with HE, 0.31 in patients without HE, and 0.34 in healthy controls; similar differences were seen in basal ganglia and cerebellum. Metabolic trapping of blood 13N-ammonia in the brain showed neither regional, nor patient group differences. Mean net metabolic flux of ammonia from blood into intracellular glutamine in the cortex was 13.4 μmol/min/L tissue in patients with cirrhosis with HE, 7.4 in patients without HE, and 2.6 in healthy controls, significantly correlated to blood ammonia. In conclusion, increased cerebral trapping of ammonia in patients with cirrhosis with acute HE was primarily attributable to increased blood ammonia and to a minor extent to changed ammonia kinetics in the brain. (HEPATOLOGY 2005;43:42–50.)
Pay for Performance Through the Lens of Medical Professionalism
Authors: Amir Qaseem
Journal: Annals of Internal Medicine (2010)

Lagging quality of care in the U.S. health care system has been a persistent problem and challenge. In the past, medical professionalism and professional certification have served as cornerstones for improving quality in health care. Among newer efforts to improve quality, pay for performance has been proposed to propel better results, but many observers are concerned that pay for performance is at odds with medical professionalism. The authors examine the potential conflicts between pay for performance and medical professionalism and conclude that properly designed pay-for-performance models can support professional objectives.
520. The Effects of Transgene and Cassette Size on Recombinant AAV2 Production and Expression
Authors: Corinne M. Goldsmith, Antonis Voutetakis, Bruce J. Baum
Journal: Molecular Therapy (2005)

Background: Recombinant Adeno-asssociated virus serotype two (rAAV2) vectors are strictly limited with regard to the size of the transgene cassette that can be accommodated (24.7 kb). Within this strict size limitation, there may be preferential sizes for the inserted cassette that can affect optimal packaging efficiency and transgene expression (Dong et al, Hum Gene Ther, 1996). In the present study, we examined if the transgene itself will affect the optimal packaging size and have constructed two series of five different-sized rAAV2 vectors, encoding either human erythropoietin (hEpo) or growth hormone (hGH).
Intracardiac and Intravascular Potentials Resulting from Electrical Activity of the Normal Human Heart
Authors: CHARLES E. KOSSMANN, ADOLPH R. BERGER, BERTHA RADER, JOSEPH BRUMLIK, STANLEY A. BRILLER, JOHN H. DONNELLY
Journal: Circulation (1950)

Electrical records were made from the interior of the right heart and attached vessels in 14 normal subjects. Technics differed somewhat from those previously reported in that simultaneously recording string galvanometers were used exclusively, and tracings were made whenever the catheter-electrode was moved within the heart. Previously unreported large positive QRS deflections were found in records from the lower part of the right atrium, from the pulmonary artery, and in two instances from within the right ventricle itself close to the base. The possible anatomical origin of these is discussed.
Loop of Henle bicarbonate accumulation in vivo in the rat.
Authors: D Z Levine, M K Byers, R A McLeod, J A Luisello, S Raman
Journal: Journal of Clinical Investigation (1979)

We have carried out perfusion studies on hydropenic and bicarbonate-loaded rats to provide direct in vivo observations on bicarbonate accumulation in the short loops of Henle. Analysis of early distal tubular fluid was made during bicarbonate-free saline perfusion from the end proximal to the early distal site, documenting accumulation of "new" bicarbonate. During perfusion in hydropenic rats, steady-state bicarbonate concentrations were suggested by early distal values of approximately equal to mM, which were independent of perfusion rate and virtually indistinguishable from bicarbonate concentration measured during free flow when filtered bicarbonate was allowed to enter the loop. Thus, loop bicarconate accumulation was apparently sufficient to allow new bicarbonate to enter at a rate comparable to that delivered to the early distal site during free flow, recognizing of course that free-flow delivery rates are the result of complex components of filtration and bidirectional fluxes. In bicarbonate-loaded rats, however, bicarbonate accumulation rates although higher than in hydropenia, were much lower than free-flow delivery rates. Furthermore, early distal bicarbonate concentrations during bicarbonate loading fell as perfusion rate increased, presumably because of a limitation to increasing ionic bicarbonate entry.
Regression of a hamster melanoma with intralesional Corynebacterium granulosum
Authors: DAVID PASLIN
Journal: British Journal of Dermatology (1976)

The present study was undertaken to compare the antitumour effects of intralesionally administered Corynebacterium granulosum, Corynebacterium parvum, BCG and saline on a hamster melanoma. Forty‐eight golden hamsters were inoculated subcutaneously with Fortner's melanotic melanoma no. 1. Twenty‐four animals bore palpable tumours which were left in situ. The remaining twentyfour animals bore palpable tumours which were excised. No non‐excised group animal showed primary tumour regression. In the excised group, the tumours generally recurred at the excision site in the C. parvum, BCG and saline‐treated animals. By contrast, the incidence of recurrence was significantly reduced by intralesional injections of C. granulosum.
Population impact of different definitions of airway obstruction
Authors: B.R. Celli, R.J. Halbert, S. Isonaka, B. Schau
Journal: European Respiratory Journal (2003)

There is currently no consensus on the criteria for diagnosing chronic obstructive pulmonary disease. This study evaluated the impact of different definitions of airway obstruction on the estimated prevalence of obstruction in a population-based sample. Using the Third National Health and Nutrition Examination Survey, obstructive airway disease was defined using the following criteria: 1) self-reported diagnosis of chronic bronchitis or emphysema; 2) forced expiratory volume in one second (FEV<sub>1</sub>)/forced vital capacity (FVC) &lt;0.70 and FEV<sub>1</sub> &lt;80% predicted (Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage IIA); 3) FEV<sub>1</sub>/FVC below the lower limit of normal; 4) FEV<sub>1</sub>/FVC &lt;88% pred in males and &lt;89% pred in females; 5) FEV<sub>1</sub>/FVC &lt;0.70 ("fixed ratio"). Spirometry in this dataset did not include reversibility testing, making it impossible to distinguish reversible from irreversible obstruction. Rates in adults varied from 77 per 1,000 (self-report) to 168 per 1,000 (fixed ratio). For persons aged &gt;50 yrs, the fixed ratio criteria produced the highest rate estimates. For all subgroups tested, the GOLD Stage II criteria produced lower estimates than other spirometry-based definitions. Different definitions of obstruction may produce prevalence estimates that vary by &gt;200%. International opinion leaders should agree upon a clear definition of chronic obstructive pulmonary disease that can serve as a population-based measurement criterion as well as a guide to clinicians.
P62 MMP10 EXPRESSION PROTECTS FROM ACUTE LIVER INJURY BUT CONTRIBUTES TO HEPATOCELLULAR CARCINOMA PROGRESSION
Authors: O. Garcia-Irigoyen, S. Carotti, M.U. Latasa, I. Uriarte, S. Morini, G. Perrone, U. Vespasiani-Gentilucci, M. Elizalde, R. Urtasun, J.A. Rodriguez, J. Orbe, J.A. Paramo, J. Prieto, C. Berasain, M.A. Avila
Journal: Journal of Hepatology (2014)
Abstract B15: Development of a chimeric saporin peptide which targets human prostatecancer cells via monocyte delivery
Authors: Jeff Eskew, Deryl Troyer, Stefan Bossmann, George Vielhauer
Journal: Cancer Research (2012)

Abstract Many attempts have been made to utilize plant and bacterial toxins to produce chimeric proteins that target and kill cancer cells; however, problems with specificity have slowed the progress of this potential therapy. We hypothesize that the specificity of these chimeric cytotoxic peptides can be improved by incorporating two layers of targeting. This will be accomplished by using the inherent tumor targeting properties of monocytes as well as engineering them to secrete a chimeric saporin peptide possessing a targeting element that is highly specific to human prostate cancer cells. Saporin is a small protein produced by soapwort that is a member of the ribosome inactivating protein (RIP) family. This family consists of some of the most potent toxins known to man, including ricin and abrin. RIPs act by gaining entry to the cell and then catalytically inactivating the ribosome. Ricin and abrin are very potent toxins because they contain two chains, a beta chain that gains entrance to the cell and an alpha chain that catalytically inactivates the ribosome. Saporin, unlike ricin or abrin, contains only the alpha chain; thus cell entry is prevented and making it, in theory, harmless unless it is attached to something that causes the cell to internalize it. In order to identify a highly specific and internalizable peptide that could be fused to a saporin molecule we screened a random 12-mer peptide bacteriophage library against the human prostate cancer cell line PC3. After several rounds of in-vitro and in-vivo biopanning we have isolated candidate peptides that appear specific and rapidly internalizable in PC3 cells. Using these peptides as targeting elements we propose to create a chimeric protein consisting of a signal peptide for secretion, a targeting peptide, and the cytotoxic saporin. This chimeric protein will be expressed in primary monocytes using a lentiviral system. Our preliminary data show that this fusion protein demonstrates profound cytotoxicity in PC3 cells within 72 hours. We have also developed an efficient orthotopic and metastatic human prostate cancer model in mice and have preliminary data showing monocyte recruitment to metastatic nodes. In conclusion, peptides that specifically target metastatic PC3 cells have been identified, in vivo, and have been linked to toxins that demonstrate potent cytotoxicity in vitro. Future studies will be to test the selective targeting of these toxic chimeric proteins, in vivo, utilizing primary and metastatic orthotopic tumor models of human prostate cancer in tumor efficacy studies. Citation Format: Jeff Eskew, Deryl Troyer, Stefan Bossmann, George Vielhauer. Development of a chimeric saporin peptide which targets human prostatecancer cells via monocyte delivery [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B15.
Livedoid vasculitis with anticardiolipin antibodies: improvement with danazol
Authors: None Wakelin, None Ellis, None Black
Journal: British Journal of Dermatology (1998)

Journal Article Livedoid vasculitis with anticardiolipin antibodies: improvement with danazol Get access S.H. Wakelin, S.H. Wakelin St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K., Search for other works by this author on: Oxford Academic Google Scholar J.P. Ellis, J.P. Ellis Princess Margaret Hospital, Swindon, SN1 4JU, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.M. Black M.M. Black St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K., Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 5, 1 November 1998, Pages 935–937, https://doi.org/10.1046/j.1365-2133.1998.02541.x Published: 01 November 1998
Physicians and Their Patients' Suicides
Authors: James Santiago Grisolia
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Dr Miles<sup>1</sup>expresses a reasoned reluctance to sanction euthanasia or physician-assisted suicide. Although I share his reluctance, plainly the status quo is unsatisfactory to patients and physicians. Since suicide remains a forbidden topic, patients already determined to commit suicide must deceive their own physicians, whereas undecided patients feel unable to bring up the issue, inhibiting the free discussion of alternatives to suicide. In terminal care, the murkiness surrounding euthanasia confounds adequate pain control and sedation; many physicians fail to give adequate treatment from exaggerated fear of hastening death, while other physicians prescribe excessively as covert euthanasia. The net result—patients fooling physicians, physicians fooling themselves, and physicians fooling others with misleading documentation. A recent survey of British physicians<sup>2</sup>demonstrates the extent of the problem: 45% had been asked by patients to actively assist death. Of these, 32% admit covertly assisting euthanasia, despite legal proscription. Quill<sup>3</sup>
Similar evolution of hepatitis B virus quasispecies in patients with incomplete adefovir response receiving tenofovir/emtricitabine combination or tenofovir monotherapy
Authors: Fabien Lavocat, Paul Dény, Christian Pichoud, Nasser Al Hawajri, Kathryn Kitrinos, Katyna Borroto-Esoda, Fabien Zoulim
Journal: Journal of Hepatology (2013)
MISSISSIPPI STATE MEDICAL ASSOCIATION
Authors: S. W. Glass
Journal: JAMA (1913)

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
Chiral discrimination in platinum anticancer drugs.
Authors: Michele Benedetti, Jaroslav Malina, Jana Kasparkova, Viktor Brabec, Giovanni Natile
Journal: Environmental Health Perspectives (2002)

In this article we review the biological activity of analogs of the antitumor drug cisplatin that contain chiral amine ligands. Interaction with DNA and formation of cross-links with adjacent purine bases are considered to be the crucial steps in the antitumor activity of this class of complexes. Because double-helical DNA has a chiral structure, interaction with enantiomeric complexes of platinum should lead to diastereomeric adducts. It has been demonstrated that DNA cross-links of platinum complexes with enantiomeric amine ligands not only can exhibit different conformational features but also can be processed differently by the cellular machinery as a consequence of these conformational differences. These results expand the general knowledge of how the stereochemistry of the platinum-DNA adduct can influence the cell response and contribute to understanding the processes that are crucial for antitumor activity. The steric requirements of the chiral ligands, in terms of configuration and flexibility, are also elucidated.
PREVENTION OF RHEUMATIC FEVER
Authors: Alan C. Siegel
Journal: JAMA (1963)

Elsewhere in this issue (p 985) Grossman and Stamler report a retrospective study of 110 first attacks of rheumatic fever. In essence, 85% of these attacks were preceded by an infection, which if properly recognized and adequately treated could have resulted in the prevention of the rheumatic fever in these individuals. During this century, morbidity and mortality from rheumatic fever and rheumatic heart disease have declined markedly in the United States. Nevertheless, these diseases have by no means been eradicated. They still are significant cripplers and killers of children and young adults, and today exact a sizeably greater toll than paralytic poliomyelitis. The data collected by Grossman and Stamler indicate that this need not be, and that it is in order to enhance the effort to prevent rheumatic fever. The relationship between initial attacks of rheumatic fever and antecedent Group A streptococcal infections, as well as the ability of adequate
TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes
Authors: Monica W.L. Leung, Shiqian Shen, Juan J. Lafaille
Journal: The Journal of Experimental Medicine (2009)

Numerous studies have highlighted the importance of high-affinity interactions between T cell receptors (TCRs) and their ligands in the selection of Foxp3+ regulatory T cells (T reg cells). To determine the role of the TCR in directing T cells into the Foxp3+ lineage, we generated transgenic (Tg) mice expressing TCRs from Foxp3+ cells. Initial analyses of the TCR Tg mice crossed with RAG-deficient mice showed that the percentage of Foxp3+ cells was very low. However, intrathymic injection and bone marrow chimera experiments showed a saturable increase of the Foxp3+ population when T reg TCR Tg cells were present in low numbers. Furthermore, when analyzing whole thymi of T reg TCR Tg RAG-deficient mice, we found significantly more Foxp3+ cells than in conventional T cell TCR Tg mice. Our results indicate that although the TCR has an instructive role in determining Foxp3 expression, selection of Foxp3+ individual clones in the thymus is limited by a very small niche.
Increased anti-Epstein-Barr virus antibodies in epidermotropic cutaneous T-cell lymphoma: a study of 64 patients
Authors: O. JUMBOU, C. MOLLAT, J.M. N'GUYEN, S. BILLAUDEL, P. LITOUX, B. DRÉNO
Journal: British Journal of Dermatology (1997)

Epstein-Barr virus (EBV) is often associated with non-Hodgkin's T-cell lymphomas and has recently been found in the lesions of mycosis fungoides and Sézary syndrome. We sought to determine whether the anti-EBV antibody profile was disturbed in mycosis fungoides and Sézary syndrome and whether there are particular profiles characteristic of disease stage. Anti-EBV antibodies (anti-VCA, -EA and -EBNA) were studied in the sera of 64 patients. An immunoenzymatic technique was used, and the results were compared with the same number of age- and sex-matched healthy controls. Patients with mycosis fungoides and Sézary syndrome developed higher anti-VCA antibody titres (median 1200) than controls (median 320). Thirty-seven patients had anti-VCA > or = 1200 vs. 19 controls (P < 0.01). These elevated anti-VCA antibody titres were associated with positive EA in 19 patients versus three controls. No differences were found between the illness stages. Anti-EBV antibodies were most often found in mycosis fungoides and Sézary syndrome when the serological profile was similar to that of cellular immune deficiencies and EBV-related non-Hodgkin's lymphoma. EBV could be involved, either directly on lymphocytes or, more likely, indirectly by chronic antigenic stimulation.
Addressing commissioning difficulties is a priority for elderly prisoners
Authors: J. Laidlaw
Journal: BMJ (2012)

Ginn highlights the difficulties of providing good health and social care to elderly prisoners in the UK.1 A prisoner’s deprivation of liberty should not result in lower quality health and social care.2

Provisions, including the Mental Health Act 1983 (MHA), are available for moving prisoners to hospital when they require healthcare …