tbuckley/cabot-search huggingface dataset:
Abstract 3826: Breast cancer metastasis suppressor-1 promoter methylation in cell free DNA provides prognostic information in non-small cell lung cancer
Authors: Ioanna Balkouranidou, Maria Chimonidou, Georgia Milaki, Emily Tsaroucha, Stelios Kakolyris, Danny Welch, Vasilis Georgoulias, Evi Lianidou
Journal: Cancer Research (2014)

Abstract Background: Breast-cancer metastasis suppressor 1 (BRMS1) gene encodes for a predominantly nuclear protein that differentially regulates the expression of multiple genes, leading to suppression of metastasis without blocking orthotopic tumor growth. The aim of the present study was to evaluate for the first time the prognostic significance of BRMS1 promoter methylation in cell free DNA (cfDNA) circulating in plasma of non-small cell lung cancer (NSCLC) patients. Towards this goal, we examined the methylation status of BRMS1 promoter in NSCLC tissues, matched adjacent non-cancerous tissues and corresponding cfDNA as well as in an independent cohort of patients with advanced NSCLC and healthy individuals. Methods: BRMS1 promoter methylation was examined in 57 NSCLC tumors and adjacent non-cancerous tissues, in cfDNA isolated from 48 corresponding plasma samples, in cfDNA isolated from plasma of 74 patients with advanced NSCLC and 24 healthy individuals. Results: BRMS1 promoter was highly methylated both in operable NSCLC primary tissues (59.6%) and corresponding cfDNA (47.9%) but not in cfDNA from healthy individuals ( 0%), while it was also highly methylated in cfDNA from advanced NSCLC patients (63.5%). In operable NSCLC, Kaplan-Meier estimates were significantly different in favor of patients with non-methylated BRMS1 promoter in cfDNA, concerning both DFI (p=0.048) and OS (p=0.007). In advanced NSCLC, OS was significantly different in favour of patients with non-methylated BRMS1 promoter in their cfDNA (p=0.003). Multivariate analysis confirmed that BRMS1 promoter methylation has a statistical significant influence both on operable NSCLC patients' DFI time and OS and on advanced NSCLC patients' PFS and OS. Conclusions: BRMS1 promoter methylation in cfDNA isolated from plasma of NSCLC patients provides important prognostic information and merits to be further evaluated as a circulating tumor biomarker. Citation Format: Ioanna Balkouranidou, Maria Chimonidou, Georgia Milaki, Emily Tsaroucha, Stelios Kakolyris, Danny Welch, Vasilis Georgoulias, Evi Lianidou. Breast cancer metastasis suppressor-1 promoter methylation in cell free DNA provides prognostic information in non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3826. doi:10.1158/1538-7445.AM2014-3826
775. An Novel Adenoviral E1 Complementary Cell for Eliminating Replication Competent Adenovirus (RCA) during Viral Production
Authors: Deborah Farson, Lucy Tao, Derek Ko, Thomas Harding, De-Chao Yu, Yuanhao Li
Journal: Molecular Therapy (2004)

Production of recombinant adenoviruses from 293 cells and other recently developed adenoviral E1-complementary cell lines have the potential to produce low levels of replication competent adenoviruses (RCA) derived from cellular DNA recombination. In most E1 complementary cells, varying lengths of the adenoviral E1A and E1B coding regions and their transcriptional regulatory structures have been used to generate the cell lines. A 3Kb fragment of the viral genome containing both the E1A and E1B coding regions (nts 560 to 3510 of adenovirus 5) is essential in developing such cell lines. This leaves open the possibility for cellular-derived E1 DNA to undergo homologous recombination with both E1-deleted replication defective and E1-modified replication competent adenoviral vectors. In order to mitigate the potential for cell-derived homologous recombination during adenovirus production, we applied a different strategy to generate E1-complementary cells. The coding sequences for adenovirus E1A and E1B were cloned into separate retroviral vectors derived from Moloney Murine Leukemia Virus (MMLV). E1A or E1B expressing transient retroviral supernatants were separately prepared from these vectors and used to co-infect cells. The A549 human lung carcinoma cell line was co-infected by the supernatants containing the MMLV-E1A and MMLV-E1B vectors. Limiting dilution and functional screens led to the isolation of adenoviral E1-complementary cell lines. These cells support the replication of E1-defective adenoviral vectors and express the E1A and E1B gene products as demonstrated by Western blot. Of note, instead of a continuous strand of adenoviral DNA, the E1A and E1B genes are separately integrated as two smaller DNA fragments. This arrangement is designed to minimize the chance of RCA generation derived from the recombination of viral DNA with cellular DNA. In addition to supporting the replication of E1-defective adenoviral vectors, further characterization of these cell lines demonstrated that they complement the replication of E1-modified replicating adenoviral vectors in which the E1 genes are under the control of tissue-specific, transcriptional regulatory elements. Comparisons of 293, PerC6, and the A549-derived E1-complementary cell lines suggest equivalent viral production. This complementation ability was stable over 10 weeks in culture and multiple passages of the cell lines. Preliminary RCA assessment suggests that these cells are superior to 293 cells and other cells in reducing the production of RCA.
Streptococcus pneumoniae endophthalmitis: a study of 36 cases with special reference to antibiotic resistance and treatment options
Authors: F. Soriano, E. Pérez-Trallero, R. Pallarés, M.A. Meseguer, A. Fleites, A. Gené, A. González, J. Liñares, J. Esteban, F. Baquero, E. Valdés, C. Muñoz-Almagro
Journal: Clinical Microbiology and Infection (2006)
Abstract 11925: Effects of Optimal Medical Therapy on Health Status in Patients With or Without PCI for Stable Coronary Disease: Results From COURAGE
Authors: Zugui Zhang, Paul Kolm, Edward Ewen, John A Spertus, William E Boden, William S Weintraub
Journal: Circulation (2014)

Background: Health status data were measured repeatedly over time in the COURAGE trial, where percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) was compared with OMT alone in reducing the risk of cardiovascular events in patients with stable coronary disease. In this study, we examined the effects of OMT on health status data. Methods: Health status was assessed with the RAND-36 and Seattle Angina Questionnaire (SAQ) at baseline, 1, 3, 6 month and annually among 2,287 patients followed for a median of 4.6 years. Medical therapy was based on guidelines for management of angina. Exercises status was evaluated via intensity and frequency of physical activity (30 to 45 minutes, 5 times/week). The nutrition status was assessed via MEDFICTS in term of the dietary goal of <7% of calories from saturated fat (score <40 vs. ≥40). Piece-wise growth curve modeling was conducted to study the factors associated with health status score changes. Results: The health status scores in both groups ...
A book that changed my practice: Problem oriented medical records
Authors: P. Savage
Journal: BMJ (2001)

As part of my senior registrar training at St Mary's in the late 1960s I spent a year working on the cardiothoracic unit. It was while wrestling, both physically and mentally, with the two, three, or even four volumes of case notes of patients coming for cardiac surgery that I thought that there must be a better way of organising them.

Help was at hand. A film of one of Lawrence Weed's presentations was shown in the medical school. His vivid demonstration of what he thought of disorganised and confusing case notes caught my imagination. Why could doctors not use a scientific methodology when recording their clinical findings? I was seized with a missionary fervour and for 35 years used the principles of the problem oriented …
History, Science, Art
Authors: John E. Skandalakis
Journal: JAMA (2003)

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
Radio: The Disease Detectives
Authors: B. Purcell
Journal: BMJ (2001)

BBC Radio 4 Wednesdays 24 January to 21 February at 9 00 pm 

In a society preoccupied with risk, attempts to demystify the role of epidemiologists are welcome, but a producer wishing to make an absorbing programme about epidemiologists certainly has his or her work cut out. However, Paul Arnold manages to strike a difficult balance. Exposing some interesting struggles between researchers and others, he skilfully uses these to explain and discuss some of the principles and pitfalls of epidemiological reasoning and practice.

Taking as its starting point the London cholera epidemic of 1854, the first programme tells the story of John Snow and the Broad Street pump. The historical insights, however, place Snow's pioneering natural experiment in context beside the …
279. Methotrexate Chemotherapy of L1210 Leukemia in Mice Transplanted with Transgenic Marrow Expressing Drug-Resistant Dihydrofolate Reductase
Authors: Joel L. Frandsen, Debra Swanson, R. Scott McIvor
Journal: Molecular Therapy (2004)

Methotrexate (MTX) is an effective chemotherapeutic agent in the treatment of several proliferative tumors, most notably acute lymphocytic leukemia, Ewings sarcoma and osteosarcoma. However, methotrexate also has considerable toxicity for normal proliferative tissues, including hematopoietic cells and cells of the gastrointestinal tract. The toxicity of methotrexate thus limits its chemotherapeutic effectiveness. MTX acts by binding to dihydrofolate reductase (DHFR) as a competitive inhibitor of the enzyme. We are investigating the possibility of expressing drug-resistant forms of DHFR in hematopoietic cells as a means of protecting the recipient from the toxicity associated with MTX chemotherapy. We previously demonstrated substantial protection of recipient mice from lethal toxicity of MTX by transplantation of transgenic marrow expressing Arg22 or Tyr22 forms of drug-resistant DHFR. Here we report that the increased MTX dose tolerance afforded by transplantation with marrow expressing the tyr22 form of drug-resistant DHFR allows for improved chemotherapy of murine L1210 leukemia. In our experimental model, animals were administered a subcutaneous dose of 10e6 L1210 tumor cells. Three days later, the animals were given a sublethal (650 cGy) dose of Cs irradiation. Our preliminary studies demonstrated that this course of treatments left a consistent amount of residual disease in the animals. One day after irradiation, animals were transplanted with 107 bone marrow cells flushed either from normal animals or from Tyr22 DHFR transgenic animals, and on the following day MTX administration was initiated. Control mice administered PBS developed tumor at a median of 12 days after subcutaneous injection of L1210 cells. Administration of 4 mg/kg MTX resulted in a considerable delay in the emergence of tumor for groups given either normal BMT or DHFR transgenic BMT. However, animals transplanted with normal marrow suffered from MTX toxicity, evidenced by reduced hematocrit, while there was no anemia observed in animals transplanted with DHFR transgenic marrow. A second experiment was conducted in the same way except that MTX was administered at a higher dose of 10 mg/kg/day. In this experiment, all control animals transplanted with normal marrow succumbed to toxicity associated with drug administration, while animals transplanted with DHFR transgenic marrow were substantially protected from drug toxicity. Appearance of tumor was delayed to a median of 28 days in comparison to 12 days for PBS administered controls. We conclude that expression of drug-resistant DHFR in hematopoietic cells confers substantial resistance to MTX, which can be used for more effective chemotherapy against L1210 leukemia in mice. These results support the application of DHFR gene transfer as strategy for improved cancer chemotherapy using MTX and other antifolates.
Abstract P379: The Burden of Hypertension in US Emergency Departments - a report from 2006-2010 HCUP Nationwide Emergency Department Sample
Authors: Lakshmi Venkitachalam, Arif Ahmed, Jeffery Hackman, Nivedita Kumari, Karen B Williams, William E Lafferty, Mary M Gerkovich
Journal: Circulation (2014)

Background: In spite of temporal advancements in medicine, hypertension (HTN) remains a leading cardiovascular risk factor with suboptimal rates of control. The burden imposed by this cardiovascular risk factor on the nation’s emergency system is not well-understood. We sought to characterize emergency department (ED) visits among adults ≥18 years that included a diagnosis of hypertension in the 2006-2010 Nationwide Emergency Department Sample. Methods: We defined hypertension using ICD-9 diagnosis codes based on the Agency for Healthcare Research and Quality indicators for potentially preventable conditions. Appropriate sampling weights were applied to obtain national estimates and 95% confidence intervals. Results: Over the 5-year period, the estimated total annual rate of ED visits among US adults was 98.3 million - 19.9% (n=19,534,992) of these visits included HTN as diagnosis. Rates of ED visits with HTN tended to increase over time [ 2006: 18.1 (17.6 - 18.6), 2007: 19.0 (18.5 - 19.5); 2008: 20.0 (19.4 - 20.5); 2009: 20.7 (20.1 - 21.3); 2010: 21.5 (20.9 - 22.1)]. Annual weighted rates of HTN varied across age groups, payer status, and neighborhood income ( Table ). In the multivariable logistic regression model, that accounted for clustering and sampling weights, the odds of ED visits with HTN was significantly lower among younger patients and those who were uninsured/self-pay, higher among Medicare recipients, and lower among patients from neighborhoods with higher median income or urban locations. Conclusion: Between 2006 and 2010, an estimated 1,953 per 10,000 visits to the ED each year included a diagnosis of hypertension among adult patients. National estimates of ED visits with HTN differ across patient and hospital characteristics, and likely represent an opportunity to monitor and address the burden of this potentially preventable condition.
Abstract 14138: Safety of Echocardiographic Contrast in Patients with Pulmonary Hypertension: A Multicenter Study
Authors: Valentin Suma, Omar Wever-Pinzon, Ameeta Ahuja, Jorge Romero, Nishtha Sareen, Sonia A Henry, Maria De Benedetti Zunino, Farhan F Chaudhry, Ramya Smitha Suryadevara, Farooq A Chaudhry
Journal: Circulation (2011)

Background: Echocardiographic contrast (EC) improves the diagnostic accuracy of suboptimal echocardiographic studies. Limited data is available regarding the safety of EC in patients with pulmonary...
Reversal of Arthritis by Human Monomeric IgA Through the Receptor‐Mediated SH2 Domain–Containing Phosphatase 1 Inhibitory Pathway
Authors: Elisabetta Rossato, Sanae Ben Mkaddem, Yutaka Kanamaru, Margarita Hurtado‐Nedelec, Gilles Hayem, Véronique Descatoire, Cédric Vonarburg, Sylvia Miescher, Adrian W. Zuercher, Renato C. Monteiro
Journal: Arthritis & Rheumatology (2015)

Rheumatoid arthritis (RA), one of the most frequent chronic inflammatory rheumatic disorders, is characterized by the presence of autoantibodies and joint infiltration by activated immune cells, leading to cartilage and bone destruction. IgA occurs predominantly as monomers (mIgA) in plasma and regulates many cell responses through interaction with the Fcα receptor type I (FcαRI). FcαRI targeting by anti-FcαRI Fab inhibits activating receptors by inducing an inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) configuration through SH2 domain-containing phosphatase 1 (SHP-1) recruitment. The aim of this study was to investigate the potential utility of mIgA for the treatment of arthritis by acting as an inducer of ITAMi signaling.The effect of plasma-derived human mIgA on inhibition of multiple heterologous receptors was evaluated on FcαRI+ cell transfectants, blood phagocytes from healthy individuals, and synovial cells from RA patients. FcαRI-transgenic mice and wild-type mice treated with mIgA were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The mice were assessed for development of arthritis using an arthritis score, and joint tissue samples were evaluated for the extent of leukocyte infiltration and expression of phosphatase.Treatment with mIgA impaired cell activation in an FcαRI-FcRγ-dependent manner, involving ITAMi signaling. Human mIgA or anti-FcαRI Fab were strongly effective in either preventing or attenuating CAIA or CIA in FcαRI-transgenic mice. Administration of mIgA markedly inhibited the recruitment of leukocytes to the inflamed joints of mice, which was associated with induction of SHP-1 phosphorylation in joint tissue cells. Moreover, mIgA reversed the state of inflammation in the synovial fluid of RA patients by inducing an ITAMi configuration.These results demonstrate a therapeutic potential of human mIgA in experimental arthritis. The findings support future clinical exploration of mIgA for the treatment of RA.
Saturation Mutagenesis of the β Subunit of the Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor Shows Clustering of Constitutive Mutations, Activation of ERK MAP Kinase and STAT Pathways, and Differential β Subunit Tyrosine Phosphorylation
Authors: Brendan J. Jenkins, Timothy J. Blake, Thomas J. Gonda
Journal: Blood (1998)
Abstract 3319: Early and Late Complications of Cardiac Resynchronisation Therapy: A Single Centre Experience Over 8 Years of 402 Patients
Authors: Syed Y Ahsan, Dominic P Rogers, James McCready, Laurence Nunn, Pier D Lambiase, Oliver R Segal, M D Lowe, Julie Sanders, Ajay Suri, Bunny Saberwal, Anthony W Chow
Journal: Circulation (2009)
Abstract 18816: Relationship of Aortic Valve Surgery and Survival in Patients with Moderate or Severe Aortic Stenosis and Left Ventricular Dysfunction
Authors: Zainab Samad, Amit N Vora, Allison Dunning, Joseph A Sivak, Linda K Shaw, John P Vavalle, Matthew W Sherwood, Paul Hofmann, Donald D Glower, Joseph A Kisslo, J. Kevin Harrison, Eric J Velazquez
Journal: Circulation (2014)

Introduction: Aortic valve replacement (AVR) for aortic stenosis (AS) carries additional surgical risk in patients with left ventricular dysfunction (LVD) but has been associated with survival benefit. The current use of AVR and its relationship to mortality in patients with moderate or severe AS and LVD is ill defined. Hypothesis: We hypothesized that AVR was underutilized among patients with moderate/severe AS and LVD, and that it was associated with lower mortality. Methods: We queried the Duke Echocardiographic Database for patients with moderate (mean gradient &gt;25 mmHg and/or peak velocity &gt;3m/s) or severe AS (mean gradient &gt;40 mmHg and or peak velocity &gt;4m/s) and LVD (left ventricular ejection fraction [LVEF] &lt;50%) from 1/1/1995-5/1/2014. We used multivariable Cox modeling to assess the relationship of AVR and all-cause mortality. Results: We identified a total of 1,634/132,804 patients with moderate (1,095, 67%) or severe (539, 33%) AS and LVD. Severe LVD (LVEF ≤35%) was present in 35% of the cohort. The median age of the cohort was 75 (IQR 67-83), and patients with moderate AS were more likely than those with severe AS to have a history of ischemic heart disease, diabetes, peripheral vascular disease, cerebrovascular disease, and renal disease (all p &lt;0.01). Median logistic EuroSCORE was 9.8 (5.5, 16.8). Median follow-up time was 1.2 years (IQR 0.2- 3.9). There were 863 deaths in the cohort. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. After multivariable adjustment, AVR with (n=270) or without CABG (n=280), compared to medical therapy was associated with lower mortality (HR=0.47 [0.38, 0.59], p&lt;0.0001) in the entire cohort. Compared to CABG alone, the combination of CABG + AVR (HR=0.19 [0.14, 0.27], p&lt;0.0001) was associated with a significant survival advantage. Conclusions: Among patients with significant AS and LVD, AVR with or without CABG is associated with significant mortality benefit and may be underutilized in this population. Further research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.
Antibody-Deficiency and Acute Nephritic Syndrome in a Patient with Homozygous Disruption of the CD81 Gene
Authors: Menno C van Zelm, Julie Smet, Françoise Mascart, Brigitte Adams, Liliane Schandené, Françoise Janssen, Alina Ferster, Jacques JM van Dongen, Mirjam van der Burg
Journal: Blood (2008)