tbuckley/cabot-search huggingface dataset:
Lilly challenges Canada's decision to strike down patents for not meeting "inventive promise"
Authors: O. Dyer
Journal: BMJ (2013)

The US drug giant Eli Lilly has filed suit against Canada, claiming that the country’s courts have arbitrarily struck down its patents. The company is seeking $500m (£315m; €375m) in alleged lost business under the terms of the North American Free Trade Agreement (NAFTA).

Two Canadian patents­—those for atomoxetine (marketed as Strattera), used to treat attention-deficit/hyperactivity disorder (ADHD), and the antipsychotic olanzapine (Zyprexa)—were voided early by …
A4.3 Adipocytes Modulate the Phenotype of Macrophages through Secreted Lipids
Authors: IR Klein-Wieringa, SN Andersen, JC Kwekkeboom, M Giera, BJE de Lange-Brokaar, GJVM van Osch, AM Zuurmond, V Stojanovic-Susulic, RGHH Nelissen, TWJ Huizinga, M Kloppenburg, REM Toes, A Ioan-Facsinay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adipose tissue secretes a wide range of soluble factors that can influence whole body metabolism. Previous studies have shown an accumulation of macrophages and an enhanced pro-inflammatory profile of these cells in adipose tissue of obese mice. Modulation of macrophages by soluble mediators released by adipocytes has been proposed as a possible mechanism underlying these changes. In humans, an increased number of macrophages in adipose tissue of obese individuals have been observed, although no clear change in macrophages phenotype could be established. Moreover, no information exists about the interaction between macrophages and adipocytes in humans. <h3>Objective</h3> In the present study, we explored the possibility that adipocytes modulate the phenotype of macrophages and studied the possible molecular pathways involved in this modulation. <h3>Results</h3> Treatment of macrophages with adipocyte-conditioned medium (ACM) resulted in a strong reduction in IL-12p40 secretion upon LPS stimulation, whereas TNFα and other cytokines remained largely unaffected. This effect was independent of the source of ACM. Interestingly, the inhibition increased with increase in Body Mass Index (BMI) of the adipocyte donor. Therefore, it was hypothesised that the effect is mediated by a soluble factor whose release is correlated to the BMI of the adipocyte donor. To this end, we measured several cytokines, adipokines and lipids present in ACM. Among these, the release of several free fatty acids (FA) and PGE<sub>2</sub> correlated with the BMI of the adipocyte donor. Further tests indicated that oleic and linoleic acid, as well as PGE<sub>2</sub> were able to inhibit IL12p40 secretion, whereas palmitic acid could not. Upon separation of ACM protein and lipid fractions, we confirmed that inhibition of IL12p40 resides mainly in the ACM lipid fraction. <h3>Conclusions</h3> These results provide first evidence that obesity-related changes in macrophage phenotype could be mediated by adipocytes in humans. These effects are mainly mediated through lipids released by adipocytes. Intriguingly, modulation appears different than in murine obesity, indicating that the immunomodulatory effects of obesity could be different in humans and mice.
Interferon Induction in Man by a Synthetic Polyanion of Defined Composition
Authors: Thomas C. Merigan, William Regelson
Journal: New England Journal of Medicine (1967)

SINCE its discovery,1 interferon has been considered to have potential value in the control of virus disease in man. Primary vaccinia infection has been blocked in human beings by preinoculation of skin sites with monkey interferon prepared in tissue culture,2 , 3 and by the use of live-virus-vaccine induction of circulating interferon before vaccinia inoculation.4 Unfortunately, although human interferon can be produced in tissue culture and appears during a variety of naturally occurring and artificially induced virus infections in man – both in serum and in infected tissue – it has not been obtained in quantities sufficient for treatment of naturally occurring . . .
TWO-YEAR CLINICAL OUTCOMES OF ACUTE MYOCARDIAL INFARCTION PATIENTS WITH MYOCARDIAL BRIDGE AND/OR CORONARY ARTERY SPASM WITHOUT OBSTRUCTIVE LESIONS
Authors: Baek Ju Yeol, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Dong Joo Oh, Myung Ho Jeong
Journal: Journal of the American College of Cardiology (2016)
RADIONUCLIDE ASSESSMENT OF VENTRICULAR FUNCTION FOLLOWING INTRA-VENOUS CLONIDINE IN CHRONIC CONGESTIVE HEART FAILURE.
Authors: W. Plauche, G. Sander, A. Quiroz, G. Thomas, T. Giles
Journal: Clinical Nuclear Medicine (1983)

Departments of Nuclear Medicine and Medicine, Tulane University and Veterans Administration Medical Center, New Orleans, Louisiana.
Correlation between Parameters of Optical Diffusion Imaging and Prognostic Factors of Breast Cancer.
Authors: J. Moon, H. Kim, H. Shin
Journal: Cancer Research (2009)

Abstract Background: Total hemoglobin (HBT) and oxygen saturation (SO2) of optical diffusion imaging might be useful to predict extensive intraductal component (EIC) and lymphovascular invasion (LVI) in patients with breast cancer.To determine if the parameters of optical diffusion imaging correlate with the prognostic factors of breast cancer.Method and materials: A total of 95 patients who underwent surgery due to breast cancer were included in our study from March to October 2008. We obtained HBT, SO2 and synthesis diagnosis index (SDI) from optical diffusion imaging. Prognostic factors including estrogen receptor, progesterone receptor, HER-2/neu, HER-1, CK5/6, p53 status, LVI, EIC, lymph node metastasis and histologic grade were reviewed from pathologic report. We correlated HBT, SO2 and SDI on optical diffusion imaging with prognostic factors using Pearson correlation coefficient test.Result: Negative EIC showed correlation with low level of HBT and positive EIC showed correlation with high level of HBT (p=0.022). Negative LVI showed correlation with high level of SO2 and positive LVI showed correlation with low level of SO2 (p=0.038). Other prognostic factor shows no significant correlation with HBT and SO2. SDI shows no significant correlation with any prognostic factors.Conclusion: HBT and SO2 on optical diffusion imaging correlated with EIC and LVI, which enable prediction of EIC and LVI in patients with breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5018.
Overdose of Extended-Release Acetaminophen
Authors: Andis Graudins, Cynthia K. Aaron, Christopher H. Linden
Journal: New England Journal of Medicine (1995)

To the Editor: A previously healthy 13-year-old girl arrived at the hospital 19 hours after ingesting two handfuls of Tylenol Extended Relief (McNeil Pharmaceuticals), a new extended-release formulation of acetaminophen containing 650 mg per caplet. Vomiting and abdominal pain began six hours after ingestion. Examination revealed tenderness of the epigastrium and right upper quadrant. The serum acetaminophen level was 89 μg per milliliter, with an alanine aminotransferase level of 180 IU per liter, a bilirubin level of 1.7 mg per deciliter, and an international normalized ratio of body weight of 1.5. The patient received an initial oral dose of 140 . . .
Hyperhomocysteinemia as a Risk Factor for Deep-Vein Thrombosis
Authors: Martin den Heijer, Ted Koster, Henk J. Blom, Gerard M.J. Bos, Ernest Briët, Pieter H. Reitsma, Jan P. Vandenbroucke, Frits R. Rosendaal
Journal: New England Journal of Medicine (1996)

Previous studies have suggested that hyperhomocysteinemia may be a risk factor for venous thrombosis. To assess the risk of venous thrombosis associated with hyperhomocysteinemia, we studied plasma homocysteine levels in patients with a first episode of deep-vein thrombosis and in normal control subjects.We measured plasma homocysteine levels in 269 patients with a first, objectively diagnosed episode of deep-vein thrombosis and in 269 healthy controls matched to the patients according to age and sex. Hyperhomocysteinemia was defined as a plasma homocysteine level above the 95th percentile in the control group (18.5 micromol per liter).Of the 269 patients, 28 (10 percent) had plasma homocysteine levels above the 95th percentile for the controls, as compared with 13 of the controls (matched odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.2). The association between elevated homocysteine levels and venous thrombosis was stronger among women than among men and increased with age. The exclusion of subjects with other established risk factors for thrombosis (e.g., a deficiency of protein C, protein S, or antithrombin; resistance to activated protein C; pregnancy or recent childbirth; or oral-contraceptive use) did not materially affect the risk estimates.High plasma homocysteine levels are a risk factor for deep-vein thrombosis in the general population.
Abstract 59: Impact of omega-3 fatty acids on obesity-induced DNA oxidation and prostate cancer progression
Authors: David A. Cavazos, Linda A. deGraffenried
Journal: Cancer Research (2010)

Abstract Obesity is associated with poor prognosis and contributes significantly to prostate cancer-related mortality. As the prevalence of obesity increases among young adult males, the contribution to prostate cancer progression and mortality are expected to rise dramatically. One potential mechanism by which obesity may promote worse outcome is through the induction of functional metabolic abnormalities known to promote inflammation and oxidative stress. Pre-clinical and clinical observations indicate that a BMI &amp;gt;30 promotes oxidative DNA damage and is associated with shorter time to PSA failure and prostate cancer mortality. Growing evidence supports a beneficial role of omega-3 (ω-3) fatty acids in delaying time to PSA failure and reducing the aggressiveness of advanced prostate cancer, however, the mechanisms are multivariate and relatively unresolved. As oxidative burden is strongly implicated in the pathogenesis of age-related diseases, including prostate cancer tumor formation, and as omega-3 fatty acids possess known antioxidant and anti-inflammatory properties, we investigated the effects of docosahexaenoic acid (DHA-22:6n-3), one component of fish oil, in reducing the effects of obesity-induced oxidative DNA damage. Preliminary data demonstrates that prostate cancer cells (LNCaP) pretreated with ω-3 fatty acids and pulsed with physiologic levels of H2O2 were preferentially sensitive to induction of growth arrest compared to normal prostate epithelial cells (PrEC). LNCaP cells pulsed with 32 uM H2O2 exhibit DNA breaks associated with translocation of NF-κB into the nucleus, whereas pretreatment with DHA prior to H2O2 treatment prevented NF-κB translocation, selectively sensitizing LNCaP cells, but not PrEC, to cell death. Further, DHA attenuated H2O2-induced NF-κB transcriptional activity and diminished expression of the downstream target, survivin. NF-κB is heavily implicated in promoting prosurvival signaling and may be critical for resistance to the chronic oxidative stress and inflammation observed in the pathogenesis of prostate cancer. Here we describe one potential mechanism by which obesity may contribute to prostate cancer and the role of ω-3 fatty acids in mitigating these affects, ultimately setting the stage for Phase III clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 59.
Amplification of mRNA from Formalin-Fixed Paraffin-Embedded (FFPE) Breast Cancer Tissues without 3' Bias and Multiplex Expression Analysis on Flow-Through Microarrays.
Authors: D. Englert, D. Wilson, S. Laken
Journal: Cancer Research (2009)

Abstract Background: FFPE samples are an abundant sample resource for validation of expression-based assays and are will suited for routine clinical testing. Analysis on microarrays enables the analysis of many transcripts from small samples. However, mRNA in FFPE sections is degraded and cross-linked, with RNA fragment sizes of a few hundred bases or less, and consequently standard methods of microarray sample preparation are not reliable unless probes are very strongly biased to the 3' end. It is not always possible to design high quality probes within this restricted region of mRNAs. Amplification of target sequences any place within transcripts would permit greater flexibility in probe design and optimization of probe sets for reliable multiplex analysis.Material and Methods: Total RNA extracted from FFPE samples was subjected to two rounds of amplification with the ExpressArt TRinucleotide kit (AmpTec), which preferentially primes cDNA synthesis near the 3'-ends of mRNAs (rather than at poly-A sites) and selects for mRNAs against ribosomal RNAs. Biotin-labeled anti-sense RNA (aRNA) was prepared from the second round cDNA with the Illumina® TotalPrep™ RNA kit (Applied Biosystems). The labeled aRNA was hybridized to probes immobilized in singlet on flow-through microarrays on the Ziplex Automated Workstation (Xceed Molecular). Performance was assessed by the analysis of titration mixtures prepared from mRNA from breast cancer and colon cancer FFPE tissue blocks.Results: Median CVs of technical replicates were less than 25%. Linear responses were observed in the analysis of the titration mixtures, and all correlations between predicted and observed expression values of the titration mixtures had R2 values greater than 0.8. The data indicated that the minimum detectable expression difference was less than two-fold. Similar signal intensities were observed for 3'-biased probes and probes several hundred bases from the 3'end, confirming the lack of 3' bias in the amplification.Discussion: The results demonstrate the feasibility of amplifying and quantifying sequences at any position within transcripts in degraded mRNA from FFPE samples. Expression differences of less than two-fold may be analyzed with tens or hundreds of probes for translational research and clinical assay development on the Ziplex Workstation. Many probes may be tested in parallel to optimize probe sets for specific tests. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3052.
ET-69 * SPECIFIC Wip1 INHIBITOR, CCT007093 ABROGATE CELL PROLIFERATION, MIGRATION AND INVASION INDUCED BY THE UVC RADIATION IN HUMAN GLIOBLASTOMA CELLS
Authors: L. Yang, Z. Zhou, D. Yao, W. Xu, H. Zhao
Journal: Neuro-Oncology (2014)

BACKGROUND: Wild-type p53-induced phosphatase (Wip1) is induced in response to stress, DNA damage. Wip1 was frequently overexpressed or amplified in breast cancer, ovarian cancer, neuroblastomas, and was accounted for poor prognosis in glioma patients. Little was known how Wip1 performed when exposed to UVC radiation in human glioblastoma cells. METHODS: Human glioblastoma Cells (U87, U251) were exposed to UVC irradiation with doses of UVC as 0,1,5,25,50 and 100 J J/m2 (J) at 254 nm. Cell proliferation of U87, U251 cells exposed to UVC radiation was investigated. And Cell viability of the U87, U251 cells subjected with CCT007093, specific Wip1 inhibitor, in doses of 0, 5, 25, 50, 100, 200 µM was modulated by CCK-8 assay. Then U87, U251 cells were subjected with 50 J per m2 of UVC irradiation combined with CCT007093, and the expression of p53, Wip1 and p38 was checked. Also the cell invasion and migration exposed to UVC combined with CCT007093 were investigated by transwell and scracth assay. RESULTS: When exposed with doses above 25, the proliferation of U87, U251 cell were inhibited obviously. The exposure to UVC radiation significantly upregulated Wip1 protein level in U87, U251 cells within 24 hours. When subjected to dose of 50 J/m2 UVC combined with 50 µM CCT007093, the protein expression of Wip1, p53 were up-regulated accompany with the downregulation of p38 protein, CCT007093 could block the expression of Wip1 induced by UVC especially in U87 cell. Meanwhile CCT007093 contributed to the inhibition of glioma cell migration and invasion induced by UVC in vitro. CONCLUSIONS: The up-regulation of Wip1 in glioblastoma cells due to UVC damage could be partly attributed to the function of p53. CCT007093, specific Wip1 inhibitor, could synergy UVC irradiation to inhibit cell proliferation, migration and invasion in human glioblastoma cells.
Screening for Chronic Obstructive Pulmonary Disease
Authors: Jill Jin
Journal: JAMA (2016)

US Preventive Services Task Force (USPSTF); Albert L. Siu, MD, MSPH; Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Karina W. Davidson, PhD, MASc; John W. Epling Jr, MD, MSEd; Francisco A. R. García, MD, MPH; Matthew Gillman, MD, SM; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, CNM, MSN, MPH; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Diane M. Harper, MD, MPH, MS; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH
Mutations in Collagen Genes as a Cause of Connective-Tissue Diseases
Authors: Jeffrey S. Flier, Lisa H. Underhill, Darwin J. Prockop
Journal: New England Journal of Medicine (1992)

FOR more than 10 years, my colleagues and I have been testing the relatively simple hypothesis that the degeneration of connective tissue characteristic of many diseases is the result of genetic defects in the collagens that provide most of the strength of the normal tissues. We and others first examined this hypothesis in relatively rare genetic diseases in which bone, cartilage, and other tissues can be so fragile as to be life-threatening early in life. More recently, we have tried to see whether the same hypothesis applies to more common diseases, such as osteoporosis, osteoarthritis, and aortic aneurysms.Structure, Function, . . .
AB0785 Use and Interest of the Toothbrush and Its Innovative Ergonomic Handle in Persons with Gripping Difficulties
Authors: L. Grange, J.N. Dachicourt, I. Constanty, J.P. Gatignol
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The impairment of hands and wrists found in certain rheumatic disorders may limit the gripping of oral hygiene instruments, thereby making brushing more difficult and possibly impacting oral health (caries, gingivitis, periodontitis, etc.). <h3>Objectives</h3> To assess the interest of the INAVA SYSTEM ergonomic toothbrush. <h3>Methods</h3> A national observational study proposed to 2705 people with gripping difficulties who are or used to be members of an association against rheumatism (Association Française de Lutte Anti-Rhumatismale, AFLAR). After giving their consent, 126 people (75% women) used the INAVA SYSTEM toothbrush for 7 days. Of the 126 people surveyed, 109 of them completed two questionnaires on satisfaction and ergonomic efficacy before/after using the tested system. <h3>Results</h3> Upon entry in the study, nearly 61% of the people brushed their teeth 1 to 2 times per day and 38% brushed their teeth 3 times per day. Gripping issues resulted in difficulties in accessing certain brushing areas in 68% of cases and limited the duration of brushing for 66% of them. These issues led 29% of patients to look for a solution that improves gripping, such as extending or thickening the toothbrush handle, opting for an electric toothbrush, or even using both hands simultaneously to brush one9s teeth. After 7 days of use of the INAVA SYSTEM toothbrush, patients gave an average overall evaluation mark of 8/10. In about 75% of cases, long last tooth brushing has been achieved by the INAVA SYSTEM, especially in patients limited by their gripping difficulties (86%). Sixty-five percent (65%) of respondents also indicated that the system has increased the accessibility in the oral cavity. <h3>Conclusions</h3> The use of the INAVA system in people with gripping difficulties had a positive impact on oral hygiene in terms of brushing duration and accessibility to dental surfaces. These two parameters are essential for the control of dental plaque which causes caries and gum diseases. In addition, 79% of respondents are convinced by the INAVA SYSTEM toothbrush and want to extend the experiment. <h3>Disclosure of Interest</h3> L. Grange: None declared, J.N. Dachicourt: None declared, I. Constanty: Employee of: Pierre Fabre Santé, J.P. Gatignol Employee of: Pierre Fabre Santé <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1257
Abstract 2951: Regulation of E2F-dependent transcription by the mTORC1 pathway
Authors: Brian K. Law, Pat E. Corsino, Mary E. Law, Stephan Jahn, Bradley Davis
Journal: Cancer Research (2011)

Abstract mTORC1 inhibitors such as rapamycin and its analogs (rapalogs) are promising anticancer agents, which are effective against some tumors, yet ineffective against others. Understanding the mechanisms controlling tumor responsiveness or resistance to rapalogs is therefore critical. Much of the anticancer activity of mTORC1 inhibitors stems from inhibition of cancer cell proliferation and suppression of the endothelial cell proliferation required for angiogenesis. Rapalogs induce a G1 cell cycle arrest, which has been attributed to suppression of the translation of proliferation-associated proteins. However the exact mechanism by which mTORC1 inhibition results in G1 cell cycle arrest is unclear. Since activation of E2F-dependent transcription is required for the G1/S-phase cell cycle transition, we examined the mechanisms by which rapamycin inhibits the expression of E2F1, which is itself encoded by an E2F-dependent gene. Rapamycin treatment decreased the binding of Cdk2 to the E2F sites of the E2F1 promoter in DNA oligonucleotide affinity purification experiments. This observation was corroborated by a decrease in Cdk2 binding to E2F4, p130, and p107, and a corresponding increase in Cdk2 binding to p27 in coimmunoprecipitation experiments. This suggests a model in which Cdk2 is recruited to E2F sites of promoters by complex formation with E2F4, p130, and p107 and functions to relieve the repression of these elements by maintaining p130 and p107 in their hyperphosphorylated forms. Consistent with this model, rapamycin treatment decreased kinase activity associated with E2F-DNA binding elements, but had little effect on overall Cdk2 activity in crude cell lysates. Rapamycin caused disruption of Cdk2/p130-, p107-, E2F4-containing complexes on E2F promoter elements. These results provide insights into how rapamycin treatment inhibits E2F-dependent transcription. It is hoped that further analysis of Cdk2/p130/E2F complexes will reveal mechanisms of tumor resistance to rapalogs and opportunities for optimizing the efficacy of mTORC1 inhibitors using combination therapies. 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 2951. doi:10.1158/1538-7445.AM2011-2951
IMPACT OF THE ABSORB BIORESORBABLE VASCULAR SCAFFOLD SURFACE AREA ON ON-TREATMENT PLATELET REACTIVITY
Authors: Lisa Gross, Dirk Sibbing, Madeleine Eickhoff, Moritz Baquet, Martin Orban, Katarina Grujic, Anne Krieg, Hans Theiss, Stefan Brunner, Daniel Teupser, Lesca Holdt, Steffen Massberg, Julinda Mehilli, Medizinische Klinik
Journal: Journal of the American College of Cardiology (2015)
TRANSCATHETER AORTIC VALVE IMPLANTATION IN PATIENTS WITH PREVIOUS EXTERNAL BEAM RADIOTHERAPY
Authors: Kathryn Dougherty, Zvonimir Krajcer, Neil Strickman, Ali Mortazavi, Richard Fish, Guilherme Silva, Jose Diez, Amy L. Paul, Raymond Stainback, Stephanie Coulter, Joseph Navarijo, Benjamin Cheong, Ross Reul, Joseph Coselli, David Ott, James Livesay
Journal: Journal of the American College of Cardiology (2016)
Albert Blair Harrington
Authors: B. May
Journal: BMJ (2013)

Albert Blair Harrington was brought up in Brisbane, Australia. He came to Britain as a young man in search of a medical training and studied for his MD at Aberdeen University. In 1939 he married Valerie White of Kiltegan, Co Wicklow, and a strong Irish connection was established. After the second world war, when he was a captain in the Royal Army Medical Corps serving in the North African campaigns, Greece, and Crete, he returned to England. He aspired to a clinical career in neurology, notably as …