tbuckley/cabot-search huggingface dataset:
Abstract 1040: The effect of Irinotecan in k-Ras wild and mutant type colon cancer cell lines.
Authors: Joo Sung Park, Jung Guk Jeon, Myoung Hee Kang, You Jin Jang, Sun Il Lee, Jae Ho Byun, Jun Suk Kim, Sang Cheul Oh
Journal: Cancer Research (2013)

Abstract Irinotecan(IRI) prevents DNA from unwinding by inhibition of topoisomerase1. Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. Recent studies, those with Irinotecan treatment has a synergistic effect appears. However, there is no study on the effect of the Irinotecan mono-treatment. In addition their roles and the underlying mechanism in anti-tumorigenic function of solid tumor, especially kras wild and mutant type colon cancer, are not yet known. Bax protein is a key mediator of apoptosis and might be related to chemosensitivity. In this work, we evaluated the anti-tumorigenic action of these Irinotecan anti-cancer agent with especially k-ras wild and mutant type colon cancer cell lines, and investigated their apoptosis-inducing effects as the potential mechanism in this process. The results show that the growth inhibitory effects of 5-fuorouracil (5-FU), Oxaliplatin(OX) produced a dose- and time dependent fashion in k-ras wild(HT29, Colo205) and mutant type(HCT116, DLD-1) colon cancer cell lines. Otherwise, Irinotecan(IRI) produced a cell growth of k-ras wild type cell lines were resistant versus that shown in the sensitive k-ras mutant type cell lines. Cell cycle analysis by FACS indicated that IRI-treated cell lines showed an increase in the proportion of cells in sub-G1 phase, compared to untreated cells. Exposure of colon cancer cells to IRI also resulted in the increase in the percentage of annexin V- positive and PI-negative cells. The results by multiple in vitro experimental model, showed that IRI induce these k-ras mutant type colon cancer cells to undergo apoptosis with increased the Bax protein and a release of cytochrome C from mitochondria, the activation of caspase9, the cleavage of PARP. But Bax protein was inactivation in k-ras wild type colon cancer cell lines. Importantly, inhibition of ERK kinase activity demonstrated that IRI-induced apoptotic pathway was regulated by the ERK signaling cascade. These data indicate that Anti-cancer agent, Irinotecan, promotes Bax mediate apoptosis of colon cancer cell lines by sequential activation of the ERK signaling pathway followed by the up-regulation of intrinsic pathway of caspase 9. Citation Format: Joo Sung Park, Jung Guk Jeon, Myoung Hee Kang, You Jin Jang, Sun Il Lee, Jae Ho Byun, Jun Suk Kim, Sang Cheul Oh. The effect of Irinotecan in k-Ras wild and mutant type colon cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1040. doi:10.1158/1538-7445.AM2013-1040
Bernard Vincent Lee
Authors: J. Scotson
Journal: BMJ (2010)

Bernard Vincent Lee came from a well-known Manchester family, which had given two Lord Mayors to the city. He began his medical career by undertaking ear, nose, and throat surgery, starting with house appointments at Manchester Royal Infirmary and later working in this specialty at Wythenshawe Hospital. He did his national service as a medical officer in the Royal Air Force, after which he worked for eight years in general practice in Carlisle. He also worked with the blood transfusion service, followed by employment in the Department …
New Holographic Process Provides Noninvasive, 3-D Anatomic Views
Authors: Andrew A. Skolnick
Journal: JAMA (1994)

A NEW holographic system for generating and displaying true-to-life, three-dimensional images of a patient's internal anatomy may help physicians make more accurate diagnoses and plan more effective treatment for a variety of clinical problems. Clinical uses of the system, which creates holographic images from digital data obtained by conventional computed tomographic (CT) or magnetic resonance (MR) scanners, were the subject of 10 scientific papers and exhibits at the 79th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA), held in Chicago, Ill. According to clinical researchers who are using the new technology, the holograms, unlike conventional ones that show only the surface of objects, produce three-dimensional images that are accurate replicas of anatomic structures. The solid-appearing yet transparent replicas, which float in space several inches in front of the holographic film, can be studied, magnified, measured, reversed, or even merged with additional holograms that show relationships
Left Ventricular and Atrial Functions in Hypertrophic Cardiomyopathy Patients with Very High LVOT Gradient: A Speckle-Tracking Echocardiographic Study
Authors: Murat Sunbul, Kursat Tigen, Tansu Karaahmet, Cihan Dundar, Beste Ozben, Ahmet Guler, Altug Cincin, Mustafa Bulut, Ibrahim Sari, Yelda Basaran
Journal: Journal of the American College of Cardiology (2013)
New Philosophies in Medical Education
Authors: Joseph W. Hess
Journal: JAMA (1970)

It is possible to look upon the multitude of changes occurring in medical education today as arising from one of two broad philosophical trends. The first is grounded in a combination of intuition, logic, and practical expedience. The second has its roots in behavioral science and educational research. The characteristics of what we will call the intuitive approach can be briefly summarized as follows: A feeling arises in one or several people in a medical school that the educational program is not as good as it might be if things were done differently. When the groundswell gains sufficient support in the power structure of the school, a committee is appointed to study the matter. The committee usually reviews what is going on in its own school and may well survey the programs of other schools in search of new ideas. A new curriculum is proposed, the pros and cons are
OC-041 IL28B haplotypes and IP-10 predict treatment response for recurrent HCV post transplant
Authors: D Joshi, I Carey, M Bruce, A Barnabas, S Knighton, M Heneghan, V Aluvihare, A Suddle, N Heaton, J O'Grady, K Agarwal
Journal: Gut (2012)

<h3>Introduction</h3> Hepatitis C virus (HCV) recurrence post liver transplant (LT) is universal. Sustained virological response (SVR) rates post LT with pegylated interferon (PEG-IFN) and ribavirin (RIB) range between 26% and 50% and are associated with significant side effects. Single nucleotide polymorphisms (SNPs) rs12979860 near the IL28B gene predict response to treatment. Strong immune T helper type 1 responses towards HCV determine also play an integral role in the outcome of infection. Interferon γ inducible protein 10 (IP-10) has been shown to correlate with treatment response in HCV mono-infection and HIV co-infected patients but limited data are available for patients in the post LT period. Our aim was to investigate whether SNPs near IL28B gene rs12979860 and pre-treatment plasma levels of IP-10 can predict treatment response in patients with recurrent HCV post LT. <h3>Methods</h3> Pre-treatment plasma samples were studied in HCV patients post LT. Plasma levels of IP-10 (pg/ml) was measured by ELISA. rs12979860 were tested by direct sequencing. All patients were treated with PEG-IFN α 2a and weight based RIB for a minimum of 48 weeks irrespective of genotype. Virological response was divided into SVR, null-response (NR) and responder relapse (RR). All results are presented as medians (range). <h3>Results</h3> 41 patients (34 male) with recurrent HCV (49% genotype one disease) were treated at a median time of 43 months (3–133) post LT. 71% of patients were maintained on tacrolimus monotherapy. Nine patients had been treated previously with PEG-IFN and RIB. Median baseline HCV viral load was 2.35E6 IU/ml. 78% of patients were commenced on a low accelerated dosage regimen (median dose PEG 135 μg, median dose RIB 800 mg). Rs12979860 haplotype CC was present in 24% (8×SVR, 2×RR), CT 59% (10×SVR, 9×NR, 5×RR) and TT in 17% (1×SVR, 6×NR). SVR was achieved by 19 patients (46%), 15 patients were NR (37%) and 7 were RR (17%). Baseline IP-10 levels correlated with serum AST (r=0.48, p=0.003), ALT (r=0.36, p=0.05), fibrosis score (r=0.33, p=0.04) and necro-inflammatory score (r=0.54, p=0.001). IP-10 levels were lower in those who achieved a SVR (116 vs 490, p&lt;0.0001). IP-10 levels were higher in the NR group compared to the SVR and RR groups (545 vs 116 vs 320, p&lt;0.0001). AUROC analysis identified IP-10 to be a significant predictor of SVR (0.84, 0.71–0.97, p&lt;0.0001). CC haplotype and IP-10 &lt;154 pg/ml had a 100% PPV for SVR. <h3>Conclusion</h3> Our data demonstrates that patients with a lower baseline IP-10 level are more likely to achieve a SVR. The IL28B CC haplotype in conjunction with a low IP-10 level predicts treatment success in recurrent HCV post LT. <h3>Competing interests</h3> None declared.
Update in Asthma 2013
Authors: Lauren Cohn, Prescott G. Woodruff
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The year 2013 brought us another step closer to understanding what can drive, influence, and ameliorate asthma.Here, we review all of the primary research in asthma published in 2013 in the American Journal of Respiratory and Critical Care Medicine and include other important asthma research focused on immunology and inflammation published in high-impact journals.Our target audience is the general pulmonary practitioner and our goal is to provide a brief annual update on the state of research being published in the Journal and how it fits into overall progress in asthma research.Because asthma research encompasses a vast range of disciplines, we review only a fraction of the exciting studies published in 2013.Overall, these works focused heavily on asthma heterogeneity, using genotypes, biomarkers, and clinical features to expand the characterization of asthma subpopulations.These works also investigated factors that induce and modify disease, such as obesity and environmental exposures, including cigarette smoke, pollution, and stress, and endogenous exposures to the respiratory tract microbiome.Mechanistic studies focused on factors that modify known biological pathways underlying asthma, including both allergic, type 2 inflammation, and nonallergic airway disease.These studies often start with a clinical finding that maps a pathway to the disease.Alternatively, these studies follow the pathways involved in a factor that is elevated in asthma and, later, to its association in different asthma subpopulations.On the basis of well-defined biological pathways in asthma, in 2013 the scientific community collected more data showing that selected subgroups of patients with asthma respond preferentially to classes of biological agents, and many of those agents continue on the path to U.S. Food and Drug Administration approval.There were also disappointing data suggesting that other therapies, based on impressive preclinical data, were ineffective.Successful clinical trials depend on years of research, and thus the more progress we can make unraveling the complexity of asthma pathogenesis, the more successful we will be in treating disease.
TRAUMATISM DURING INTUBATION—ITS PREVENTION AND TREATMENT.
Authors: JOHANN VON BOKAY
Journal: JAMA (1901)

In studying the literature of the O'Dwyer method of intubation we should really feel that everything that can be said in favor of or against it has been mentioned, and still we find a great deal requiring more careful elaboration; thus, the question of decubitus has not been given as much prominence as it deserves. True it is that all intubators must have found laryngeal ulceration resulting from pressure of the tube, and O'Dwyer, and later, Variot, the chief of the Trousseau Hospital, and his associate, Bayeux, besides Glover, Baudrand, and Marie Schultz, are among those whose attention has been directed to this particular portion of the subject. The French collective pediatric study of Grancher, Marfan and Comby on this subject appeared in a publication entitled "Laryngites Traumatiques Consecutives Au Tubage." This is the most valuable contribution to literature that can possibly be imagined. It seems as though the enthusiasts
Abstract 220: BRCA1 regulates p53 target expression via DNp73
Authors: Kimberly A. Scata, Wafik S. El-Deiry
Journal: Cancer Research (2011)

Abstract In response to cellular stresses, the tumor suppressor gene p53 is stabilized and transactivates several categories of target genes, including cell cycle arrest genes and pro-apoptotic genes. These sets of genes are not activated simultaneously and how the differential expression of these targets occurs has been the subject of intense scrutiny. We have previously shown that overexpression of BRCA1 stabilizes p53 but fails to activate the expression of its proapoptotic targets. When BRCA1 is overexpressed, the posttranslational modifications of p53 are the same as those that occur in response to stress and p53 is still able to bind to the promoters of the proapoptotic targets. In order to determine how BRCA1 regulates p53 gene expression, we've explored the role of the p53 family members. We find that BRCA1 is able to induce DNp73, a dominant negative acting isoform of p73. Unexpectedly, we found that BRCA1 upregulates DNp73 expression, an isoform of the p53 family member p73 lacking the transactivation domain, which has been previously implicated in cell survival. This observation has important implications for understanding the selectivity of p53-dependent transcription as well as the tumor suppressive action of BRCA1 that favors DNA repair over cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 220. doi:10.1158/1538-7445.AM2011-220
Bronchial Asthma Associated with Intestinal Parasites
Authors: David C. H. Tullis
Journal: New England Journal of Medicine (1970)

Of 201 cases of bronchial asthma, ova or larvae of one or other of three intestinal parasites were found in the stools in 198. Over 90 per cent has ascariasis, 12 patients strongyloidiasis, and two Necator americanus. None of these three parasites were found in a group of allergy-free controls.
Acetaminophen Does Not Impair Clearance of Zidovudine
Authors: Fred R. Sattler, Richard Ko, Diana Antoniskis, Mark Shields, Jordan Cohen, John Nicoloff, John Leedom, Robert Koda
Journal: Annals of Internal Medicine (1991)

Objective: To determine whether concurrent treatment with acetaminophen and zidovudine impairs clearance of zidovudine, thereby increasing the risk for zidovudine-induced hematologic toxicity. Design: Dose escalation, drug interaction study. Setting: University clinical research center. Patients: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. Interventions: Acetaminophen and 200 mg of zidovudine simultaneously every 4 hours. For 13 patients, the unit dosage of acetaminophen was 325 mg for 3 days; for 8 patients, the dosage was 650 mg for 3 days; and, for 6 patients, the dosage was 650 mg for 7 days. Measurements: Zidovudine clearance and production of the glucuronide conjugate of zidovudine were assessed after acetaminophen treatment. Main Results: Neither zidovudine clearance nor production of the glucuronide conjugate of zidovudine was impaired after treatment with acetaminophen. Clearance of zidovudine was actually accelerated by 5%, 11%, and 33% with the three acetaminophen regimens, respectively (P = 0.002 by analysis of variance; P = 0.04 for linear trend when changes in the area-under-the-curve for zidovudine were compared). Conclusion: Because serum concentrations of zidovudine decrease after the coadministration of acetaminophen, a pharmacokinetic interaction between zidovudine and acetaminophen is unlikely to increase the risk for hematologic toxicity associated with zidovudine.
A SYSTEMATIC REVIEW FOR SUDDEN CARDIAC DEATH IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS WITH MYOCARDIAL FIBROSIS: A CMR LGE STUDY
Authors: Sahadev T Reddy, Antonio Tito Paladino Filho, Nackle Jibran Silva, Mark Doyle, June Yamrozik, Robert W.W. Biederman
Journal: Journal of the American College of Cardiology (2012)
Ideas of Life and Matter: Studies in the History of General Physiology 600 B.C.-1900 A.D.
Authors: Gert H. Brieger
Journal: JAMA (1969)

What distinguishes the living from the nonliving? How do the living systems maintain their organization? What is the role of psychic factors on biological phenomena? These questions, which in one form or another still concern us, have a very long history. In this book, Dr. Hall, professor of biology at Washington University, St. Louis, has summarized the various responses that have been given to these perplexing queries since the time of the pre-Socratic philosophers six centuries before Christ. Ever since the early Greek investigators of nature, almost every generation has asked what Hall describes as classic questions. The physiologists of various periods have investigated nutrition, locomotion, sensation, and reproduction—some of the processes that distinguish life from the nonliving. One of the basic points Hall makes is that not only do the same questions recur, but also the analytical procedures for their investigation are those found in ancient Greek science. Modern
Efficient, Long-term Hepatic Gene Transfer Using Clinically Relevant HDAd Doses by Balloon Occlusion Catheter Delivery in Nonhuman Primates
Authors: Nicola Brunetti-Pierri, Gary E Stapleton, Mark Law, John Breinholt, Donna J Palmer, Yu Zuo, Nathan C Grove, Milton J Finegold, Karen Rice, Arthur L Beaudet, Charles E Mullins, Philip Ng
Journal: Molecular Therapy (2008)

Helper-dependent adenoviral vectors (HDAd) are devoid of all viral coding sequences and are thus an improvement over early generation Ad because they can provide long-term transgene expression in vivo without chronic toxicity. However, high vector doses are required to achieve efficient hepatic transduction by systemic intravenous injection, and this unfortunately results in dose-dependent acute toxicity. To overcome this important obstacle, we have developed a minimally invasive method to preferentially deliver HDAd into the liver of nonhuman primates. Briefly, a balloon occlusion catheter was percutaneously positioned in the inferior vena cava to occlude hepatic venous outflow. HDAd was injected directly into the occluded liver via a percutaneously placed hepatic artery catheter. Compared to systemic vector injection, this approach resulted in substantially higher hepatic transduction efficiency using clinically relevant low vector doses and was accompanied by mild-to-moderate acute but transient toxicities. Transgene expression was sustained for up to 964 days. These results suggest that our minimally invasive method of delivery can significantly improve the vector's therapeutic index and may be a first step toward clinical application of HDAd for liver-directed gene therapy.
THU0540 Toll like Receptor 2 (TLR2) Induces Mitochondrial Dysfunction and Activation of the NLRP3 Inflammasome in Rheumatoid Arthritis
Authors: M. Connolly, M. Biniecka, J. McCormick, T. McGarry, D.J. Veale, U. Fearon
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Activation of the NLRP3 inflammasome by microbial and environmental stimuli enables the caspase -1-dependent processing and secretion of IL-1β. While the inflammasome has traditionally been thought to regulate infection and inflammation, impaired mitochondrial metabolism may mediate this process. <h3>Objectives</h3> In this study we examined the interplay between the inflammasome and mitochondrial function following TLR2 activation. <h3>Methods</h3> Mitochondrial mutagenesis was assessed by Random Mutation Capture Assay. Primary RASFC were stimulated with a TLR2 agonist, PAMCSK, in the presence of absence of N-Acetyl Cysteine (NAC). IL-1β and IL-18 expression was examined by PCR. Nlrp3 expression was assessed by real-time PCR and Western blot. In parallel the effect of an TLR endogenous ligand, A-SAA, on RASFC function was examined in the presence of a specific neutralising anti-TLR2 mAb (1μg/ml) and matched IgG isotype control Ab (1μg/ml). RASFC proliferation, adhesion, chemokine expression, migration and invasion were assessed by proliferation assays, flow cytometry, Taqman PCR, ELISA, wound repair and transwell assays. Finally to establish whether A-SAA activates TLR2 Human embryonic kidney (HEK) -TLR2 or -TLR4 cells were cultured in the presence of A-SAA and NFκB luciferase activity was examined. <h3>Results</h3> PAM3CYSK4 and A-SAA significantly induced mitochondrial mutagenesis in RA synovial explants cultures (p&lt;0.05). PAM3CYSK4 and A-SAA significantly induced NLRP3 mRNA and protein expression. TLR2-induced IL-6, IL-8, IL-1, IL-18 expression were significantly inhibited in presence of NAC and ROS inhibitor (all p&lt;0.05). In parallel, A-SAA-induced RASFC proliferation, ICAM-1 expression, invasion and migration was significantly inhibited in the presence of anti-TLR2 (all p&lt;0.05), suggesting its role as an endogenous TLR2 ligand. Finally we demonstrated that A-SAA induced TLR2 mediated NF-κB lucifearse activity (p&lt;0.05), with no effect observed for NFκB in HEK-TLR4 cells. <h3>Conclusions</h3> This is the first study to demonstrate that mitochondrial dysfunction may be involved in regulation of downstream inflammasome activation. Furthermore we suggest that TLR2 induced pro-inflammatory effects in RA may in part be activated by endogenous secretion of A-SAA from the synovium at the site of inflammation. <h3>Disclosure of Interest</h3> : M. Connolly: None declared, M. Biniecka: None declared, J. McCormick: None declared, T. McGarry: None declared, D. Veale Grant/research support: AbbVie, Pfizer, MSD, Roche, Consultant for: Pfizer, Roche, Speakers bureau: Pfizer, Roche, MSD, Abbott, U. Fearon: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5351
Serum metabolome analysis by 1H-NMR reveals differences between chronic lymphocytic leukaemia molecular subgroups
Authors: D A MacIntyre, B Jiménez, E Jantus Lewintre, C Reinoso Martín, H Schäfer, C García Ballesteros, J Ramón Mayans, M Spraul, J García-Conde, A Pineda-Lucena
Journal: Leukemia (2010)
Cost effectiveness of adjuvant bile salt treatment in extracorporeal shock wave lithotripsy for the treatment of gall bladder stones.
Authors: J P Nicholl, B Ross, P C Milner, J E Brazier, L Westlake, B Kohler, E Frost, B T Williams, A G Johnson
Journal: Gut (1994)

The relative cost effectiveness of adjuvant urso and chenodeoxycholic acid treatment in extracorporeal shockwave lithotripsy (ESWL) has been assessed as part of a pragmatic randomised controlled trial of ESWL as a treatment of gall bladder stones. Of the first patients with gall stone volume &lt; 4 cm3 randomised to ESWL in the main trial, 24 were randomised to have ESWL alone and 26 to have adjuvant bile acid treatment, one of whom died before the end of the 12 month follow up period. At 12 months after treatment, differences in gall stone clearance between ESWL alone (3/24 (13%) clear, 5 (21%) referred for surgery) and ESWL and bile acids (6/25 (24%) clear, 2 (8%) referred for surgery) were not significant (p = 0.36, log rank test). Patients in both groups had substantial and significant health gains (according to biliary pain frequency and severity, Nottingham Health Profile scores, visual analogue scale symptom scores, and complications) but there were no significant differences between the groups. Improvements in both groups usually occurred within a few weeks of treatment and were unrelated to gall stone clearance. Costs were greater in the bile salt group (95% confidence intervals for estimated cost difference: 90 pounds to 630 pounds). If the purpose of treatment is symptom relief rather than gall stone clearance then adjuvant bile salt treatment seems to be unnecessary.