tbuckley/cabot-search huggingface dataset:
A Sceptic's Medical Dictionary, by Michael O'Donnell
Authors: J P Bunker
Journal: BMJ (1997)

Michael O'Donnell: BMJ Books, £14.95, pp 208 ISBN 0 7279 1204 6

This is a light hearted collection of quips, anecdotes, and aphorisms that slyly feeds the reader some serious comments on the state of medical practice and clinical research. To give a flavour of the book, here is a small selection that I found provocative.

The entries are presented under somewhat arbitrary categories. Under “Faith,” which Dr O'Donnell defines as a “valuable ally in achieving a ‘cure’ and a dangerous enemy in assessing it,” he offers the following from Sir Peter Medawar: “Exaggerated claims for the efficacy of a medicament are very seldom the consequence of any intention to deceive; they are usually the outcome of a kindly conspiracy in which everybody has the very best intentions. The patient wants to get well, his physician wants to have made him better, and the pharmaceutical company would have liked …
850. Quantitative Analysis of Non-Viral Gene Therapy in a Three-Dimensional Liver Tissue Construct
Authors: Nathan C. Tedford, David W. Jackson, Karel Domansky, Linda G. Griffith, Douglas A. Lauffenburger
Journal: Molecular Therapy (2004)

Successful delivery of DNA lies at the heart of gene therapy, and its feasibility in treating a number of diseases depends on the continued development of more effective gene delivery vectors. While vectors based upon recombinant viruses have shown high transfection efficiencies, they may also pose certain health risks to patients and can be difficult to target to individual cell or tissue types of interest. Non-viral vectors look to offer a safer alternative and can be engineered to more effectively treat a specific cell type, tissue, or pathology, but these vectors are still plagued with low transfection levels. Many barriers exist in the successful trafficking of these non-viral complexes to the nucleus. Current evaluations of non-viral gene delivery treatments in more clinical settings often focus on a single barrier at a time, and as a result, may not lead to an overall improvement in gene delivery. Concurrently, more quantitative or systematic in vitro experiments may not correlate well with in vivo data. A scaled up and improved three-dimensional, perfused bioreactor has been designed and built that allows for the long-term culture of primary hepatocytes. Within the microfabricated flow channels of this reactor, cells self assemble over time into tissue structures that more closely mimic hepatic morphology and phenotype than conventional two-dimensional culture systems. By studying non-viral gene delivery in this system, quantitative experiments and experimentally-driven computational models can be developed that may better describe how a vector will perform in vivo. Methodologies in density gradient electrophoresis (DGE) have been adapted to obtain greater resolution in subcellular fractionation. An experimental scheme has been developed which utilizes a newly constructed DGE device that has demonstrated proof of principle for the separation and collection of the vesicular organelles that play an important role in gene delivery. Combined with quantitative downstream assays for both the DNA plasmid and the polymer carrier, vector dynamics can now potentially be tracked at cell entry, progressive stages of vesicular trafficking and escape, and nuclear import, providing data sets which may in turn lead to more accurate and predictive mathematical models. Through a systematic iteration of quantitative experiments and computational simulations, these models will be fine-tuned for different polymer carriers administered to the hepatic tissue constructs, potentially allowing for optimization of specific vector properties and increased success of non-viral approaches.
Abstract 1472: The differential expression of miRNAs in breast cancer cell lines
Authors: Checo J. Rorie, Brianna L. Arrington, Sherette S. Godfrey, Armeshia S. McCoy, Kashenya M. Gurley
Journal: Cancer Research (2014)

Abstract Breast cancer is a heterogenous disease that is the second leading cause of death amongst women in the United States. Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer characterized by its loss of estrogen, progesterone and HER2 receptor expression which limits its targets for effective drug therapies. Micro Ribonucleic Acids (miRNAs) are a class of small, endogenous non-coding ribonucleic acids that seem to play an essential role in gene regulation. Changes in the patterns of miRNA expression profiles are serving as potential biomarkers for tumor diagnosis, prognosis of disease-specific outcomes, and the prediction of therapeutic responses in cancer. We analyzed miRNA array (Agilent) expression profiles in triple negative breast cancer cell lines (HCC70, HCC1806, MDA-MB-157) and non-cancerous (AG11132) African American women breast cell lines. We revealed that the TNBC cells exhibited a different miRNA expression pattern when compared to the normal breast cancer cell line. We analyzed the hybridization data files using standard Microsoft Excel techniques and verified our findings using PARTEK Genomics Suite. We combined the data sets from the TNBC cell lines and compared the miRNA array expression profiles to the normal control cell line AG11132. We revealed that there were significant dysregulation of miRNAs including those of the let-7 family, miR-16, miR-31, and miR-25b-1, miR34a, and miR-95 in the triple negative cells as compared to the normal cells. These miRNAs have been described in previous scientific studies to be associated with tumorigenesis in breast cancer. These studies are initial observations that we will follow up with molecular techniques such as real-time PCR and siRNA to validate the results in order to establish more direct correlations to miRNAs and their roles in triple negative breast cancer. Citation Format: Checo J. Rorie, Brianna L. Arrington, Sherette S. Godfrey, Armeshia S. McCoy, Kashenya M. Gurley. The differential expression of miRNAs in breast cancer cell lines. [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 1472. doi:10.1158/1538-7445.AM2014-1472
Abstract 18386: Using Social Media as a Method of Increasing Organ Donation
Authors: Martin Cadeiras, Mohammad Soroya, Sagar Patel, Charlotte Starling, Gene Lim, Kevin Dong, Ronaldo Menezes, Mario Deng
Journal: Circulation (2014)

Background:  The lack of consent to organ donation is the main limiting factor for heart transplantation in the United States. Limited knowledge is available about using social media to change health behavior. Social and parasocial interactions are highly effective in increasing engagement with audiences by appropriate public influencers. We hypothesized that a Social Network (SN) intervention that engages members with short, specific content through public influencers is effective in improving attitudes about organ donation.   Method:  We disseminated public information related to organ donation to assess efficacy of engagement in social media sources through paid and organic campaigns. We used Facebook as a social media platform to engage audiences using three different methods of content delivery. The paid campaign ran for seven days without any other active intervention, followed by a one month organic phase where an audience was created and content delivered by engaging public influencers. Effectiveness was measured by click-through rates (CTR), and engagement. We analyzed each phase of the intervention and compared them against the industry averages.   Results:  The first campaign used emotionally driven content and resulted in 140 clicks in a population of 24,574 people, with a unique people reach of 127. The CTR (number of clicks/number of times shown) was 0.253% and unique (u) uCTR 0.517%. This campaign resulted in a 23% increase in engagement. In the organic phase, emotionally driven content resulted in 21.1% uCTR, Infographics 33.2%, and short educational videos 7.6%. All results performed exceptionally well above the industry average within the non-profit sector which was 0.21%. Computing engagement, emotionally driven stories and infographic driven content resulted in very high engagements, 12.3% and 14.6% respectively. The average engagement as determined by Salesforce Facebook Data Analytics within the same industry had a range of 0.5%-0.1%.   Conclusion:  Establishing a community on a social network before tailoring content resulted in the best engagement. Combined with identifying peer influencers, it is a highly effective strategy in engaging populations to stimulate a dialogue for higher consent rates than traditional campaigns.
Nonviral liposomal gene delivery to mouse and human bladder cancer in vitro, in vivo, and ex vivo
Authors: Qing Hui Wu, Edmund Chiong, Ratha Mahendran, Kesavan Esuvaranathan
Journal: Clinical Cancer Research (2007)

C25   PURPOSE: To establish a more effective therapeutic strategy against advanced bladder cancer, we investigated the efficacy of gene transfer to bladder cancer cell lines in vitro, to murine bladder cancer in vivo and to human bladder cancer tissue ex vivo as well as its therapeutic efficacy in mouse bladder cancer model using a liposome based transfection system.  METHOD: Transient transfection was performed using a cationic lipid N-[1-(2,3-dioleoyloxyl)propyl]-N,N,N-trimethylammoniummethyl sulfate, methyl-beta-cyclodextrin-solubilized cholesterol and plasmid DNA carrying coding sequence for marker genes or cytokine genes. The in vitro expression of transgene was evaluated by ELISA and luciferase assay. The expression of the transgene in situ was confirmed by x-gal staining. Mice bearing orthotopic tumors were treated with plasmid DNA/liposome complex by intravesical instillation twice a week for 3 weeks.  RESULTS: The expression level of cytokines in transfected cell lines was increased significantly. Human bladder cancer explants were also successfully transfected. The transfection system was robust within human physiological concentration range of some urinary constituents, and was only affected by extreme concentrations of urea and protein. In situ gene transfer to bladder tumors was accomplished via intravesical instillation of plasmid DNA/liposome complex after a single 2 h in situ transfection. The tumor incidence in the treatment groups was dramatically decreased from 76.9% in the control group to 15.4-30.8% in the treatment groups.  CONCLUSION: We demonstrate the feasibility of non-viral transduction of human bladder cancer samples using a clinically relevant procedure. In the orthotopic mouse bladder cancer model, successful inhibition of tumor cell growth could be obtained with cytokine gene therapy. The results suggest that our liposome transfection system appears to be a promising method for gene therapy of bladder cancer in vivo.
IL‐5 expression and release from human CD34 cells <i>in vitro</i>; <i>ex vivo</i> evidence from cases of asthma and Churg–Strauss syndrome
Authors: A. Bossios, M. Sjöstrand, A.‐K. Dahlborn, K. Samitas, C. Malmhäll, M. Gaga, J. Lötvall
Journal: Allergy (2009)

Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease.CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed.Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma.CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.
Abstract 18257: Cardiovascular Response to Energy Drink Consumption in Healthy Adults
Authors: Anna Svatikova, Naima Covassin, Krishen Somers, Filip Soucek, Tomas Kara, Lukas Ruzek, Jan Bukartyk
Journal: Circulation (2014)

Introduction: An increasing number of healthy adults consume energy drinks to enhance their physical and mental performance. Energy drinks contain caffeine and multiple other “natural” stimulants and their combined effects on cardiac hemodynamics in healthy individuals are unclear. Hypothesis: We hypothesized that drinking a commercially available energy drink, Rockstar , compared to a placebo drink, increases resting blood pressure and heart rate in healthy adults, and these increases would be further accentuated by stress conditions. Methods: We enrolled 25 healthy, normotensive subjects (14 males), aged 29±1 years, with body mass index 24.5±1 kg/m 2 , in a randomized, double-blind, placebo-controlled, crossover study. Each subject consumed a placebo drink and a commercially available Rockstar energy drink (473 ml), in random order on two separate study days. Blood pressure and heart rate responses were recorded and compared before and 30 minutes after drink consumption, both at rest and then in response to physical, mental and cold stressors. Results: The Rockstar energy drink induced a 6±1% increase in resting systolic blood pressure, compared to 3±1% with the placebo drink (P=0.0078). Diastolic blood pressure increased by 7±1% vs 0±1% with the placebo drink (P=0.0007; Figure 1). Heart rate increased similarly in both groups, by 5±2% in the energy drink group vs. 7±2% in the placebo group. Blood pressure and heart rate increases during the stress stimuli (sustained handgrip, mental stress and cold stress) did not differ between energy drink and placebo. Conclusions: Drinking a commercially available Rockstar energy drink significantly increases resting blood pressure in young healthy adults. Blood pressure increases are not further accentuated by exercise, mental or cold pressor stress stimuli. These hemodynamic changes induced by energy drink consumption could predispose to cardiovascular events.
A database of restriction endonuclease buffers
Authors: Todd Richmond
Journal: Genome biology (2000)

This simple but incredibly useful tool for molecular biologists allows the user to select one or more restriction endonuclease enzymes and determine which of the enzyme buffers provided by New England Biolabs, Boehringer Mannheim, Gibco BRL, Fermentas or Stratagene can be used in a restriction enzyme digest.
Effect of Direct Current Shocks on Left Atrial Mechanical Function in Patients With Structural Heart Disease 11This study was funded in its entirety by The Royal Melbourne Hospital Cardiology Department Clinical Research Fund.
Authors: Paul B Sparks, Rajeev Kulkarni, Jitendra K Vohra, Harry G Mond, Shenthar Jayaprakash, Anthony G Yapanis, Leeanne E Grigg, Jonathan M Kalman
Journal: Journal of the American College of Cardiology (1998)
Levodopa and the Progression of Parkinson's Disease
Authors: Stanley Fahn, David Oakes, Ira Shoulson, Karl Kieburtz, Alice Rudolph, Anthony Lang, C Warren Olanow, Caroline Tanner, Kenneth Marek
Journal: New England Journal of Medicine (2004)

The clinical data suggest that levodopa either slows the progression of Parkinson's disease or has a prolonged effect on the symptoms of the disease.In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter.The potential long-term effects of levodopa on Parkinson's disease remain uncertain.
Novel mutations in yeast topoisomerase II that confer hypersensitivity to mAMSA.
Authors: Anna T. Rogojina, John L. Nitiss
Journal: Cancer Research (2006)

5522   Topoisomerase II (Top2) is the principal target of several important anti-cancer agents. Top2 targeting agents in clinical use are referred to as topoisomerase poisons, because these compounds convert an enzyme essential for DNA metabolism into an agent that generates a unique type of DNA damage: a protein-linked double strand break. There are two broad classes of Top2 poisons: DNA intercalators, such as doxorubicin and mAMSA, and agents that have negligible interactions with DNA, such as etoposide and teniposide. Although there has been much structural and biochemical information on eukaryotic Top2, the mechanism of drug action has remained elusive. One standard approach to studying drug:protein interactions, the identification of drug resistant Top2 mutants, has proven disappointing, probably because drug resistance can occur non-specifically through mutations that reduce Top2 activity. We developed an alternate approach, the isolation and characterization of mutants of Top2 with enhanced drug sensitivity. We isolated several mAMSA hypersensitive alleles of yeast Top2, and have begun to characterize their biochemical activities. Mutations changing Pro473 to Leu (homologous to Pro485 in human TOP2α) or Gly737 to Ser (homologous to Gly760 in human TOP2α) both confer 50-fold increases in sensitivity to mAMSA in yeast cells. The mutant proteins have been purified, and encode active enzymes, although the Pro473Leu mutant protein has reduced strand passage activity compared to the wild type enzyme. The mutant enzymes exhibit elevated levels of mAMSA induced DNA cleavage, consistent with the observed drug hypersensitivity in vivo. We have directly demonstrated that Pro473Leu protein exhibits decreased religation in the presence of mAMSA compared to the wild type protein, consistent with the elevated levels of cleavage observed with the mutant protein. Interestingly, the Pro473Leu mutant also exhibits greater sensitivity to enzymatic inhibition by intercalators such as ethidium bromide than the wild type protein. Our results demarcate two distinct domains important for the action of DNA intercalating agents. While it is not surprising that Gly737 affects the action of intercalating agents, since is near a DNA binding domain of the enzyme, the strong effect of the Pro473Leu mutation is surprising and implicates regions of the enzyme that do not directly participate in DNA binding in the action of intercalating Top2 poisons. These results also provide important new reagents for understanding the action of an important class of Top2 targeting drugs.
Abstract 17165: Impact of Physical Activity Levels on Death or Heart Failure Related Hospitalizations in Patients with Heart Failure: a Sub study of the HART Trial (NCT00018005)
Authors: Ashvarya Mangla, Rami Doukky, Jonathan Kaplan, Eisuke Segawa, Elizabeth Avery, DeJuran Richardson, Lynda H Powell
Journal: Circulation (2014)

Background:  It is agreed that aerobic exercise can improve the outcome of patients with heart failure (HF). However, the impact of sedentary life style on HF outcome among patients not participating in a regimented aerobic exercise program is unknown.   Methods:  We analyzed data from Heart failure Adherence and Retention Trial (HART) which enrolled NYHA class II and III HF patients. Questionnaire was used to assess self-reported weekly physical activity levels. Patients were divided into 3 groups: sedentary (walking    Results:  HART enrolled 902 patients. Data on physical activity were available on 673 patients. There were 246 primary outcome events. Median follow up was 30 months. After adjusting for univariate predictors of outcome, there was no difference in outcome between sedentary and partially active patients (HR 1.12; P=0.48). There was a non-statistically significant trend towards worse outcomes in sedentary patients compared to active patients (HR 1.43, P=0.09) (Figure 1).   Conclusion:  Regular physical activity appears to be associated with lower risk of death or HF hospitalization in patients with HF who are not participating in a regimented aerobic exercise program, consistent with the “on-treatment” analysis of the HF-ACTION trial. Sedentary life style does not seem to be associated with increased risk of death or HF hospitalization as compared to partially active life style.
Abstract 802: Synergistic effect of curcumin on FL118 efficacy in colon cancer
Authors: Xiang Ling, Nishant Gandhi, Boyang Jiao, Dhyan Chandra, Fengzhi Li
Journal: Cancer Research (2014)

Abstract Colorectal cancer is the third most commonly diagnosed cancer in the United States and may cause about 50,830 deaths in 2013. Therefore, there is an unmet need for new therapeutic strategies. Combination of natural compounds with pharmacological small molecular inhibitors to increase anticancer efficacy while minimizing toxicity is an attractive approach for management of cancer. Curcumin, a natural dietary compound, has been shown to inhibit multiple cancer cell signaling pathways involved in survival, proliferation, apoptosis, angiogenesis and metastasis. FL118, a novel camptothecin derivative and an IAP (inhibitor of apoptosis) inhibitor, significantly attenuates colon cancer cell growth in vitro and tumor growth in vivo. In the current study, we report that curcumin enhances FL118 anti-cancer efficiency in colon cancer cell models. MTT and cell death detection ELISA assays were used for quantification of cell viability and apoptosis, respectively, in colon cancer HCT8 and SW620 cells. The synergistic effect of curcumin in combination with FL118 treatment on colon cancer growth inhibition was further analyzed by the Combination Index (CI) equation developed by Chou-Talalay using a CalcuSyn program (Biosoft, Cambridge, UK). Our data demonstrated that curcumin shows a synergistic growth inhibitory effect with FL118 in multiple colon cancer cells (p&amp;lt;0.05). Furthermore, combinational treatment can significantly enhance apoptotic cell death induced in comparison with either FL118 or curcumin treatment alone (p&amp;lt;0.05). In HCT8 colon cancer cells, a combination of 10µM curcumin with 0.3-20 nM FL118 treatment for 72 h showed a strong synergistic effect (CI &amp;lt; 0.5) in cell growth inhibition. Mechanistically, the combination treatment-enhanced cell growth inhibition and apoptosis are associated with alteration of the expression of cell death and cell cycle related genes. In conclusion, we propose that combination of curcumin with FL118 might provide a novel therapeutic strategy in colon cancer treatment. Citation Format: Xiang Ling, Nishant Gandhi, Boyang Jiao, Dhyan Chandra, Fengzhi Li. Synergistic effect of curcumin on FL118 efficacy in colon 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 802. doi:10.1158/1538-7445.AM2014-802