tbuckley/cabot-search huggingface dataset:
Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation
Authors: Maurizio Vitadello, Jannie Ausma, Marcel Borgers, Antonio Gambino, Dino C. Casarotto, Luisa Gorza
Journal: Circulation (2001)

Background —Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regulated protein GRP94, which is essential for cell viability, occur in the presence of chronic atrial fibrillation. Methods and Results —Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immunologic approach. In goats, atrial fibrillation was induced and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels doubled in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect to normal atria and returned to control levels in atrial myocardium of cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase occurred within cardiomyocytes. Significantly, increased levels of GRP94 were also observed in samples from human fibrillating atria. In the absence of signs of myocyte irreversible damage, the GRP94 increase in fibrillating atria is comparable to GRP94 levels observed in perinatal goat myocardium. However, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas inducible HSP70, a cytoplasm stress protein that is expressed in perinatal goat hearts at levels comparable to those observed in the adult heart, shows a significant increase in chronic fibrillating atria. Conclusions —Our data demonstrate a large, reversible increase in GRP94 in fibrillating atrial myocytes, which may be related to the appearance of a protective phenotype.
Abstract LB-362: The MEK inhibitor selumetinib (AZD6244 - ARRY-142886) prevents lung metastasis in a triple-negative breast cancer (TNBC) xenograft model
Authors: Chandra Bartholomeusz, Dadbin Ali, Hitomi Saso, Kimie Kondo, Paul Smith, Gabriel N. Hortobagyi, Naoto T. Ueno
Journal: Cancer Research (2012)

Abstract Patients with TNBC are negative for estrogen receptor, progesterone receptor, and HER2 expression, and have a very poor prognoses because tumors often metastasize, leading to death. Preventing metastasis as well as inhibiting the tumor growth, is crucial to improving the prognosis of TNBC. We previously showed that patients with ERK2-overexpressing TNBC were at higher risk of death than those with low-ERK2-expressing tumors. Interestingly, when we treated the TNBC cells lines MDA-MB-231 and SUM-149 with the MEK1/2 ATP uncompetitive kinase inhibitor (selumetinib) at concentrations of 0.1 and 1.0 μM, it did not reduce cell viability in a two-dimensional (2D) cell culture. However, in a three-dimensional (3D) cell culture model, selumetinib changed the mesenchymal phenotype of TNBC to an epithelial phenotype. Cells undergoing epithelial-mesenchymal transition are well known to potentially contribute to the metastatic process and have increased ability to form mammospheres. Thus, we hypothesized that targeted inhibition of the MEK-ERK pathway by selumetinib may prevent lung metastasis in TNBC. In the present study, we observed that SUM-149 cells treated with selumetinib (0.1, 1.0 μM) exhibited cell-cycle arrest at G1 but did not exhibit apoptosis indicated by an increased proportion of cells at sub-G1 phase. Both SUM-149 and MDA-MB-231 cells treated with selumetinib exhibited significant inhibition of anchorage-independent growth, an indicator of in vivo tumorigenicity (P&amp;lt;0.005). In addition, in SUM-149 cells and MDA-MB-231, treatment with selumetinib (0.01, 0.1,1.0 and 10μM) suppressed formation of mammospheres in a dose-dependent manner. Next, to determine the role of the MEK-ERK pathway in the prevention of TNBC metastasis, we used a metastatic TNBC animal model established with MDA-MB-231-LM2-4175 (lung metastatic subpopulation) cells transfected with a luciferase gene that were injected intravenously into the tail vein of mice. We observed that mice treated with selumetinib had significantly fewer lung metastases than did control mice injected with a vehicle (P&amp;lt;0.05, 2-sided t test.) These findings support a crucial role for the MAPK pathway in metastasis and suggest that ERK pathway might provide clinical benefit by preventing metastasis. Targeted inhibition of the MEK-ERK pathway with selumetinib may be a novel approach to treatment of TNBC metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-362. doi:1538-7445.AM2012-LB-362
Hector MacDonald Cameron
Authors: Lesley Morrison
Journal: BMJ (2006)

Pioneer of powered prosthetic limbs and fetal heart monitorsDavid Simpson, who was disabled by a war wound, retrained from accountancy to physics to devise solutions for medical problems.In the 1950s, when orthopaedic engineering was in its infancy, he pioneered the design and manufacture of controllable artificial limbs.He designed monitoring
Long-Term Prognostic Value of Tc-99m Tetrofosmin Myocardial Gated-SPECT Imaging in Asymptomatic Patients After Percutaneous Coronary Intervention
Authors: Panagiotis Georgoulias, Nikolaos Demakopoulos, Chara Tzavara, Stavroula Giannakou, Varvara Valotassiou, Ioannis Tsougos, Petros Xaplanteris, Ioannis Fezoulidis
Journal: Clinical Nuclear Medicine (2008)

Purpose: To evaluate the long-term prognostic value of Tc-99m tetrofosmin myocardial gated-SPECT in asymptomatic patients after coronary artery stenting. Materials and Methods: We included 246 consecutive patients in the study. All patients underwent exercise gated-single photon emission computed tomography (SPECT) myocardial imaging 5 to 7 months after percutaneous coronary intervention (PCI) and were followed for a mean period of 8.3 years (SD = 2.9). Myocardial scintigrams were evaluated calculating the summed stress score (SSS), summed rest score, and summed difference score (SDS) indexes. Cardiovascular death and nonfatal myocardial infarction were considered hard cardiac events, whereas late revascularization (>3 months after myocardial SPECT) procedures were considered to be soft events. Cox proportional hazard models were applied to evaluate the association between several variables and the investigated outcome. Results: During the follow-up period, hard cardiac events occurred in 32 (13%) patients (cardiac death occurred in 12 patients and nonfatal myocardial infarction in 20 patients). In addition, 60 (24.4%) patients underwent a late revascularization procedure. When multiple Cox regression analysis was implied, the factors that remained significant in the final model for soft events were SSS, SDS, and angina during exercise testing. In addition, SSS, SDS, and left ventricular dilatation were independently associated with hard cardiac events as defined from the results of multiple analysis. However, SSS and SDS were the only independent predictors for both hard and soft events. Conclusions: Tc-99m tetrofosmin myocardial perfusion imaging (MPI), performed 6 months post-percutaneous coronary intervention, has an independent and powerful clinical value to predict hard and soft cardiac events in asymptomatic patients after PCI.
Careless talk may cost lives in attributing adverse events to ADP receptor antagonists
Authors: M. J Green
Journal: BMJ (2002)

EDITOR—Dakik et al in their article suggest an association between the prescription of an ADP receptor antagonist (ticlodipine) with the onset of acute arthritis.1 We would like to express a note of caution. This article follows a previous one discussing another ADP receptor antagonist (clopidogrel) and the development of acute arthritis.2 These drugs are increasingly used in combination with aspirin for the prevention of thrombosis after coronary artery stenting and have been shown to be safe and efficacious. 3 4 It is …
Abstract 5399: A novel treatment for triple-negative breast cancer using intrinsic magnetized paclitaxel
Authors: Masanari Umemura, Ayako Makino, Itaru Sato, Xianfeng Feng, Kayoko Oda, Makoto Ohtake, Satoshi Izuka, Maki Iwai, Kosuke Matsuo, Haruki Eguchi, Yoshihiro Ishikawa
Journal: Cancer Research (2014)

Abstract Background: We previously reported the identification of a novel nano-organic compound, EI236, an anti-cancer agent with intrinsic magnetic property. In addition to anti-cancer effect, its ferromagnetic property contributes to unique features.1) It can be attracted by a magnet. 2) It can be visualized by magnetic resonance imaging (MRI). Hereby, we have identified the key mechanism that contributes to magnetism by X-ray crystallographic analysis, and succeeded in generating a novel paclitaxel with intrinsic magnetism; this is a single paclitaxel compound, and is not a paclitaxel encapsulated in micelle with magnetic particles. Our aim is to examine its effect on triple negative-breast cancer (TNBC) cells. Material and Method: The magnetization of the magnetized paclitaxel was measured with a superconducting quantum interference device (SQUID) (Quantum Design MPMS7 system). Breast cancer cells, MDA-MB-453 (TNBC) and MCF7 (Non-TNBC), were obtained from RIKEN Bioresource center. Cell proliferation assay was performed using a commercially available kit, XTT Cell Proliferation Assay Kit. Apoptotic cells were stained with Annexin V, allophycocyanin conjugate and 7-amino-actinomycin D, and measured by fluorescence activated cell sorting (FACS), to evaluate early and late apoptosis. Cell cycle analysis was performed using The Cycletest™ Plus DNA Reagent Kit and assessed using FACS. Results: Plots of magnetization versus magnetic field revealed that the magnetized paclitaxel exhibits magnetic property in SQUID. Magnetized paclitaxel was easily attracted by a commercial bar magnet. Magnetized paclitaxel exhibits greater anti-cancer effect than original paclitaxel in TNBC and Non-TNBC cells in a dose-dependent manner. Magnetized paclitaxel induced apoptosis and G2/M arrest in cell cycle analysis in a dose-dependent manner, suggesting that magnetized paclitaxel retained the original anti-cancer property. In MRI T2 -weighted imaging, signal intensity was changed in a concentration-dependent manner with magnetized paclitaxel, but not with commercial available paclitaxel. Conclusion: These results suggested that various conventional anti-cancer drugs might be similarly magnetized, leading to novel drug development in future cancer chemotherapy. Citation Format: Masanari Umemura, Ayako Makino, Itaru Sato, Xianfeng Feng, Kayoko Oda, Makoto Ohtake, Satoshi Izuka, Maki Iwai, Kosuke Matsuo, Haruki Eguchi, Yoshihiro Ishikawa. A novel treatment for triple-negative breast cancer using intrinsic magnetized paclitaxel. [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 5399. doi:10.1158/1538-7445.AM2014-5399
O84 LIVER STIFFNESS ASSESSED BY FIBROSCAN IS A MAJOR PROGNOSTIC FACTOR IN PRIMARY SCLEROSING CHOLANGITIS
Authors: C. Corpechot, F. Gaouar, A. El Naggar, A. Kemgang, D. Wendum, R. Poupon, F. Carrat, O. Chazouillères
Journal: Journal of Hepatology (2014)
Ku70 and Poly(ADP-Ribose) Polymerase-1 Competitively Regulate β-Catenin and T-Cell Factor-4–Mediated Gene Transactivation: Possible Linkage of DNA Damage Recognition and Wnt Signaling
Authors: Masashi Idogawa, Mitsuko Masutani, Miki Shitashige, Kazufumi Honda, Takashi Tokino, Yasuhisa Shinomura, Kohzoh Imai, Setsuo Hirohashi, Tesshi Yamada
Journal: Cancer Research (2007)

Formation of the T-cell factor-4 (TCF-4) and beta-catenin nuclear complex is considered crucial to embryonic development and colorectal carcinogenesis. We previously reported that poly(ADP-ribose) polymerase-1 (PARP-1) interacts with the TCF-4 and beta-catenin complex and enhances its transcriptional activity. However, its biological significance remains unexplained. Using immunoprecipitation and mass spectrometry, we found that two Ku proteins, Ku70 and Ku80, were also associated with the complex. Knockdown of Ku70 by RNA interference increased the amount of beta-catenin associated with TCF-4 and enhanced the transcriptional activity. PARP-1 competed with Ku70 for binding to TCF-4. Treatment with bleomycin, a DNA-damaging alkylating agent, induced polyADP-ribosylation of PARP-1 protein and inhibited its interaction with TCF-4. Bleomycin conversely increased the amounts of Ku70 coimmunoprecipitated with TCF-4 and removed beta-catenin from TCF-4. We propose a working model in which the transcriptional activity of TCF-4 is regulated by the relative amount of Ku70, PARP-1, and beta-catenin proteins binding to TCF-4. Identification of the functional interaction of Ku70 as well as PARP-1 with the TCF-4 and beta-catenin transcriptional complex may provide insights into a novel linkage between DNA damage recognition/repair and Wnt signaling.
Reversible Ovarian Ablation or Chemotherapy: Are We Ready for Quality of Life to Guide Adjuvant Treatment Decisions in Breast Cancer?
Authors: Pamela J. Goodwin
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.07.966 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14610047 Reversible Ovarian Ablation or Chemotherapy: Are We Ready for Quality of Life to Guide Adjuvant Treatment Decisions in Breast Cancer? Pamela J. GoodwinxPamela J. GoodwinSearch for articles by this author Show More Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada https://doi.org/10.1200/JCO.2003.07.966 Full Text PDF Figures and Tables "Reversible Ovarian Ablation or Chemotherapy: Are We Ready for Quality of Life to Guide Adjuvant Treatment Decisions in Breast Cancer?." Journal of Clinical Oncology, 21(24), pp. 4474–4475© 2003 by American Society of Clinical Oncology
In vivo gene therapy of type I diabetic mellitus using a cationic emulsion containing an Epstein Barr Virus (EBV) based plasmid vector
Authors: Hyuk Sang Yoo, Osam Mazda, Hyeon Yong Lee, Jin Chul Kim, Seok Min Kwon, Jung Eun Lee, Ick Chan Kwon, Hesson Jeong, Yu Seok Jeong, Seo Young Jeong
Journal: Journal of Controlled Release (2006)
Effect of gender and ITPA polymorphisms on ribavirin-induced anemia in chronic hepatitis C patients
Authors: Thomas-Matthias Scherzer, Albert Friedrich Stättermayer, Rudolf Stauber, Andreas Maieron, Michael Strasser, Hermann Laferl, Remy Schwarzer, Christian Datz, Karoline Rutter, Sandra Beinhardt, Petra Steindl-Munda, Harald Hofer, Peter Ferenci
Journal: Journal of Hepatology (2013)
PSGL-1/selectin and ICAM-1/CD18 interactions are involved in macrophage-induced drug resistance in myeloma
Authors: Y Zheng, J Yang, J Qian, P Qiu, S Hanabuchi, Y Lu, Z Wang, Z Liu, H Li, J He, P Lin, D Weber, R E Davis, L Kwak, Z Cai, Q Yi
Journal: Leukemia (2012)
S59 Evaluating The Clinical Utility Of Xpert(R) Mtb/rif For The Diagnosis And Management Of Tuberculosis In A High Burden Region Of The Uk
Authors: J. Kim, B. O'Connor, H. Patel, N. Perera, M. Wiselka, G. Woltmann, P. Haldar
Journal: Thorax (2014)

<h3>Introduction</h3> The importance of Xpert<sup>®</sup> MTB/RIF (GeneXpert) for the rapid confirmation of tuberculosis (TB) and indicator for drug resistance is now well established for high burden, resource poor countries, with a high prevalence of smear positive pulmonary disease. The phenotype of disease differs significantly in high income countries like the UK with fewer smear positive cases and more extra-pulmonary disease. The role of GX in this setting is unclear. <h3>Objectives</h3> To evaluate how GeneXpert was being used in local practice and determine factors that influenced test performance. <h3>Methods</h3> We performed a retrospective analysis of all GeneXpert tested patient samples between October 2011 and April 2014. Out of area sample requests and unprocessed specimens were excluded. Positive GeneXpert results were categorised as very low, low, medium and high. Sensitivity and specificity analyses excluded clinically diagnosed TB without supporting evidence and stratified samples by type and smear status. Statistical analyses were computed on SPSS (v.16). <h3>Results</h3> 217 assays from 193 patients were included for analysis. 101 patients (52%) were treated for TB (74 pulmonary). A clinical diagnosis of TB was made in In 14 patients. 145 samples (68%) were from the respiratory tract. The remainder were categorised as: fluid (44); tissue (15) and pus (9). Overall 68 (32%) samples were AFB smear positive and 111 (52%) samples were mycobacteria culture positive (80 <i>M.tuberculosis</i>). There were 78 (36%) GeneXpert positive results. The assay had superior performance for diagnosis of TB and predicting <i>M.tuberculosis</i> culture positive outcomes in AFB smear positive compared with smear negative samples (table). For smear negative, culture positive samples, false negative GeneXpert results were associated with a significantly longer time to culture (mean difference 10.4 days, p = 0.006). For smear negative GeneXpert positive samples, the mean time to positive diagnosis was reduced by 13.3 days but this did not alter the time to starting treatment. <h3>Conclusion</h3> In our practice, GeneXpert has high specificity to reliably inform a positive TB diagnosis but lacks sensitivity in smear negative disease to reliably exclude the diagnosis. The decision to start treatment continues to be governed by clinical suspicion in this group.
Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial
Authors: Willemien A Nienhuis, Ymkje Stienstra, William A Thompson, Peter C Awuah, K Mohammed Abass, Wilson Tuah, Nana Yaa Awua-Boateng, Edwin O Ampadu, Vera Siegmund, Jan P Schouten, Ohene Adjei, Gisela Bretzel, Tjip S van der Werf
Journal: The Lancet (2010)
Dynamics of glomerular ultrafiltration in the rat. VIII. Effects of hematocrit.
Authors: B D Myers, W M Deen, C R Robertson, B M Brenner
Journal: Circulation Research (1975)

This study was undertaken in an effort to examine the effects of selective variations in systemic hematocrit on the preglomerular, glomerular, and postglomerular micocirculation in the rat. By isovolemic exchange transfusions, systemic hematocrit (control 51 ml/100 ml) was either reduced (21 ml/100 ml, N equal 7 rats) or elevated (62 ml/100 ml, N equal 7). Single nephron glomerular filtration rate varied inversely and filtration fraction varied directly with the changes in hematocrit. The fall in filtration fraction with decreased hematocrit was due to a decline in the measured glomerular transcapillary hydraulic pressure difference and to a marked increased in the initial glomerular plasma flow rate. Afferent (RA)and efferent (RE) arteriolar resistance declined with the fall in hematocrit; RA fell proportionately more than did RE. The rise in filtration fraction with the elevation in hematocrit was due to a marked increase in in part due to a relatively greater rise in RE than in RA. These findings provide an attractive explanation for the general tendency for filtration fraction to vary directly with hematocrit in anemic and polycythemic states in man.
Improving Chronic Disease Care by Adding Laypersons to the Primary Care Team
Authors: Richard Adair, Douglas R. Wholey, Jon Christianson, Katie M. White, Heather Britt, Suhna Lee
Journal: Annals of Internal Medicine (2013)

Background: Improving the quality and efficiency of chronic disease care is an important goal. Objective: To test whether patients with chronic disease working with lay “care guides” would achieve more evidence-based goals than those receiving usual care. Design: Parallel-group randomized trial, stratified by clinic and conducted from July 2010 to April 2012. Patients were assigned in a 2:1 ratio to a care guide or usual care. Patients, providers, and persons assessing outcomes were not blinded to treatment assignment. (ClinicalTrials.gov: NCT01156974) Setting: 6 primary care clinics in Minnesota. Patients: Adults with hypertension, diabetes, or heart failure. Intervention: 2135 patients were given disease-specific information about standard care goals and asked to work toward goals for 1 year, with or without the help of a care guide. Care guides were 12 laypersons who received brief training about these diseases and behavior change. Measurements: The primary end point for each patient was change in percentage of goals met 1 year after enrollment. Results: The percentage of goals met increased in both the care guide and usual care groups (changes from baseline, 10.0% and 3.9%, respectively). Patients with care guides achieved more goals than usual care patients (82.6% vs. 79.1%; odds ratio, 1.31 [95% CI, 1.16 to 1.47]; P < 0.001); reduced unmet goals by 30.1% compared with 12.6% for usual care patients; and improved more than usual care patients in meeting several individual goals, including not using tobacco. Estimated cost was $286 per patient per year. Limitations: Providers' usual care may have been influenced by contact with care guides. Last available data in the electronic health record were used to assess end points. Conclusion: Adding care guides to the primary care team can improve care for some patients with chronic disease at low cost. Primary Funding Source: The Robina Foundation. Chinese translation
On Therapeutic Equivalency and the Antisubstitution Laws
Authors: Donald O. Schiffman
Journal: JAMA (1973)

The comparative bioavailability of a drug in similarly formulated preparations is becoming a subject of considerable interest and importance to the physician. Drugs usually are not administered as pure compounds but are combined with materials such as binders, excipients, lubricants, preservatives, or other substances generally considered to be pharmacologically inert. The resultant blend, granulation, or pill mass is packed into capsules, compressed into tablets, or manipulated into any one of many other physical forms. Until recently, the pharmacopeias that specify and describe the standards for preparations of drugs have been constructed largely on the premise that only the quantity and quality of the active drug determines the efficacy of the final preparation. This tenet is no longer valid. Currently, an overwhelming body of evidence is accumulating that indicates that the manner in which a composite medication is produced from its component parts can exert a major influence on the rate
The Value of the Autopsy in Three Medical Eras
Authors: Lee Goldman, Robert Sayson, Stanley Robbins, Lawrence H. Cohn, Michael Bettmann, Monica Weisberg
Journal: New England Journal of Medicine (1983)

To determine whether advances in diagnostic procedures have reduced the value of autopsies, we analyzed 100 randomly selected autopsies from each of the academic years 1960, 1970, and 1980 at one university teaching hospital. In all three eras about 10 per cent of the autopsies revealed a major diagnosis that, if known before death, might have led to a change in therapy and prolonged survival; another 12 per cent showed a clinically missed major diagnosis for which treatment would not have been changed. Among 1980 autopsies, renal disease and pulmonary embolus were less common causes of death than before, but systemic bacterial, viral, and fungal infections increased significantly and were missed clinically 24 per cent of the time. The introduction of radionuclide scans, ultrasound, and computerized tomography as diagnostic procedures did not reduce the use of conventional tests in patients who subsequently died and were studied by autopsy. Over-reliance on these new procedures occasionally contributed directly to missed major diagnoses. We conclude that advances in diagnostic technology have not reduced the value of the autopsy, and that a goal-directed autopsy remains a vital component in the assurance of good medical care.