tbuckley/cabot-search huggingface dataset:
Abstract 5559: Novel synthetic pyridyl analogues of CDDO-Im with improved stability and their potential use in cancer prevention
Authors: Martine Cao, Evans Onyango, Charlotte Williams, Darlene Royce, Gordon Gribble, Michael Sporn, Karen Liby
Journal: Cancer Research (2015)

Abstract Synthetic oleanane triterpenoids are non-cytotoxic, multifunctional drugs with a broad spectrum of applications for prevention and treatment of cancer and for many other chronic diseases. CDDO-Im, 1[2-Cyano-3,12-dioxooleana-1,9(11-dien-28-oyl] imidazole, synthesized more than a decade ago, is one of the most potent triterpenoids known to date with marked anti-inflammatory, cytoprotective, antiproliferative, differentiative and proapoptotic activity on various human and murine tumor cell lines. However, pharmacokinetics of CDDO-Im are not optimal. Therefore, three new pyridyl analogues of CDDO-Im, namely CDDO-3P-Im, CDDO-2P-Im and CDDO-4P-Im, have been synthesized and screened for their possible use as chemopreventive or chemotherapeutic drugs. At low nanomolar concentrations, they were equivalent to CDDO-Im for induction of differentiation in U937 leukemia cells and at higher doses they induced apoptosis. As inflammation and oxidative stress contribute to carcinogenesis, we also assessed their cytoprotective potential. The new compounds suppressed inducible nitric oxide synthase expression in RAW264.7 macrophage-like cells and significantly induced heme oxygenase-1 and NADPH quinone reductase mRNA and protein levels in lung cancer cells as well as in various mouse tissues. Most importantly, pharmacokinetic studies performed in vitro in human plasma and in vivo revealed superior stability for each new analogue. While CDDO-Im was almost completely degraded after 30 min (&amp;lt; 12% of starting material remaining) in human plasma, the new compounds were more stable with &amp;gt; 50% still detectable. Six hours after gavage, much higher concentrations of the new derivatives were found in mouse liver, lung, pancreas and kidney in contrast to CDDO-Im. Thus, the new pyridyl analogues have better bioavailability, and because of their potent anti-inflammatory activity and improved stability, they will be tested in vivo in relevant carcinogenesis models. Citation Format: Martine Cao, Evans Onyango, Charlotte Williams, Darlene Royce, Gordon Gribble, Michael Sporn, Karen Liby. Novel synthetic pyridyl analogues of CDDO-Im with improved stability and their potential use in cancer prevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5559. doi:10.1158/1538-7445.AM2015-5559
Epidemiology and outcome of candidaemia in patients with oncological and haematological malignancies: results from a population-based surveillance in Spain
Authors: M. Puig-Asensio, I. Ruiz-Camps, M. Fernández-Ruiz, J.M. Aguado, P. Muñoz, M. Valerio, A. Delgado-Iribarren, P. Merino, E. Bereciartua, J. Fortún, M. Cuenca-Estrella, B. Almirante
Journal: Clinical Microbiology and Infection (2015)
CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL
Authors: Patrick R. Hagner, Hon-Wah Man, Celia Fontanillo, Maria Wang, Suzana Couto, Mike Breider, Chad Bjorklund, Courtney G. Havens, Gang Lu, Emily Rychak, Heather Raymon, Rama Krishna Narla, Leo Barnes, Gody Khambatta, Hsiling Chiu, Jolanta Kosek, Jian Kang, Michael D. Amantangelo, Michelle Waldman, Antonia Lopez-Girona, Ti Cai, Michael Pourdehnad, Matthew Trotter, Thomas O. Daniel, Peter H. Schafer, Anke Klippel, Anjan Thakurta, Rajesh Chopra, Anita K. Gandhi
Journal: Blood (2015)
Prothrombotic Genetic Risk Factors in Young Survivors of Myocardial Infarction
Authors: D. Ardissino, P.M. Mannucci, P.A. Merlini, F. Duca, R. Fetiveau, L. Tagliabue, M. Tubaro, M. Galvani, F. Ottani, M. Ferrario, J. Corral, M. Margaglione
Journal: Blood (1999)
Fitzgerald Trait
Authors: Hidehiko Saito, Oscar D. Ratnoff, Robert Waldmann, Joseph P. Abraham
Journal: Journal of Clinical Investigation (1975)

The prolonged partial thromboplastin time observed in the plasma of a 71-yr-old asymptomatic man was related to the deficiency of a hitherto unrecognized agent. The patient's plasma also exhibited impaired surface-mediated fibrinolysis and esterolytic activity and impaired generation of kinins and of the property enhancing vascular permeability designated PF/Dil. The patient's plasma contained normal amounts of all known clotting factors except Fletcher factor (a plasma prekallikrein) which was present at a concentration of 10-15% of pooled normal plasma. Fletcher trait plasma, however, contained normal amounts of the agent missing from the patient's plasma and corrected the defects in clotting, fibrinolysis, and vascular permeability. Fletcher trait plasma was less effective in correcting generation of kinins and esterolytic activity, presumably because of the patient's partial deficiency of prekallikrein. The site of action of the factor deficient in the patient's plasma appeared to be subsequent to the activation of Hageman factor and plasma prekallikrein. A fraction of normal plasma, devoid of other clotting factors, corrected the defect in clotting in the patient's plasma; a similar fraction of the patient's plasma did not correct this abnormality. No evidence yet exists pointing to the familial nature of the patient's defect. Tentatively, the patient's disorder may be referred to by his surname as Fitzgerald trait, and the agent apparently deficient in his plasma as Fitzgerald factor.
Tissue issues: Clinical and research implications of diagnostic biopsy practices
Authors: Kelly J. Bethel
Journal: Clinical Cancer Research (2010)

Abstract Tissue Issues for Researchers: Why the pathologist does NOT want to give you human tumor tissue...and how to get it anyway. Or: Why you should befriend a pathologist. Overview: More research should be done using human tumor tissue.This is very hard for many logistical, organizational, and sociological reasons.Befriend a pathologist. Involve them early during the design phase. Fund their time.So you want some human tumor tissue...Tissue banks exist, with well-annotated tumor samples, sometimes with clinical follow up information.This tissue is either frozen or paraffin embedded.Tissue arrays are available, which are very efficient and allow for good QC because one can cut a section and actually see what cells are there, and then punch out a corresponding core of tissue from the block to use for experiment.Expensive, not necessarily tailored to your experiment, and not fresh tissue. Fresh tissue: No, we don't want to give you any...Pathologists control tissue in a hospital setting, where most cancer surgeries take place.Biopsies are hard won tiny fragments of people — we have to bully the other doctors into getting us enough in the first place.Resections usually provide lots of tissue but it takes a bunch of extra time and judgment to collect them fresh and carefully annotate them for you, and place them in special media and make sure they get picked up and handled promptly. How do we get the tissue to make the diagnosis? From whom do we get it? Diagnostic adequacy rate of sampling procedures is related to type of biopsy.Research samples are considered second priority after adequate diagnostic material is obtained. Suggestions for optimizing your chances of getting some.
Abstract 13141: Long-Term Dietary Nitrite and Nitrate Deficiency Causes Metabolic Syndrome-Like Phenotypes in Mice
Authors: Masato Tsutsui, Mika Kina-Tanada, Taro Uchida, Haruaki Kubota, Mayuko Sakanashi, Toshihiro Matsuzaki, Katsuhiko Noguchi, Junko Nakasone, Yusuke Ohya
Journal: Circulation (2014)

Background:  We previously reported that mice lacking all three nitric oxide (NO) synthase isoforms exhibit metabolic syndrome-like phenotypes, suggesting a crucial role of NO in preventing metabolic syndrome. It has recently been discovered that NO is produced from the NO metabolites, nitrite (NO 2  − ) and nitrate (NO 3  − ). NO 3  −  is rich in green leaf vegetables, such as spinach and lettuce. Based on the background, in this study, we tested our hypothesis that long-term dietary NO 2  − /NO 3  −  deficiency leads to metabolic syndrome in mice.   Method and Results:  We prepared amino acid-based low NO 2  − /NO 3  −  food pellets in which the contents of L-arginine, carbohydrate, protein, fat, and calorie were identical with regular food pellets. We also prepared ultrapure drinking water in which NO 2  − /NO 3  −  levels were not detected. The low NO 2  − /NO 3  −  food pellets plus the ultrapure drinking water (the low NO 2  − /NO 3  −  diet) or regular food pellets plus tap water (the regular NO 2  − /NO 3  −  diet) was administered in male wild-type C57BL/6 mice for 12 weeks (n=6-12). After the feeding, plasma NO 2  − /NO 3  −  levels, plasma biochemical levels, and plasma adiponectin levels were assessed by the Griess method, colorimetric method, and enzyme-linked immunosorbent assay, respectively. The plasma NO 2  − /NO 3  −  levels were markedly more reduced in the low NO 2  − /NO 3  −  diet group than in the regular diet group. There were no significant differences in food intake or body weight between the two groups. Intriguingly, visceral fat weight (epididymal white adipose tissue weight), plasma total cholesterol levels, and plasma glucose levels in intraperitoneal glucose tolerance test were all significantly increased in the low NO 2  − /NO 3  −  diet group as compared with the regular diet group (all  P  2  − /NO 3  −  diet group compared with the regular diet group ( P    Conclusions:  These results provide the first evidence that long-term dietary NO 2  − /NO 3  −  deficiency causes metabolic syndrome-like phenotypes in mice, identifying the specific dietary ingredient that causes metabolic syndrome even in the absence of excess calorie intake.
Abstract 12745: Basigin Promotes Cardiac Fibrosis and Failure in Response to Chronic Pressure-Overload in Mice
Authors: Kota Suzuki, Kimio Satoh, Ikeda Shohei, Kenji Kadomatsu, Hiroaki Shimokawa
Journal: Circulation (2014)

Background: Basigin (Bsg) is a transmembrane glycoprotein that activates matrix metalloproteinases (MMPs), promotes inflammation and is strongly expressed in cardiac tissues of patients with dilated cardiomyopathy. However, the role of Bsg in the pathogenesis of cardiac hypertrophy and failure remains to be elucidated.

Methods and Results: We performed transverse aortic constriction (TAC) in wild-type (WT) mice, and thereafter examined the time-course for 4 weeks. Importantly, Bsg expression was enhanced in the left ventricle (LV) after TAC in a time-dependent manner. To further elucidate the roles of Bsg, we examined whether cardiac responses to chronic pressure-overload were ameliorated in Bsg+/- mice. Echocardiography revealed that Bsg+/- mice showed less hypertrophy (P<0.05), less LV end-diastolic diameter (P<0.01), and preserved LV fractional shortening (35.32±1.60 vs. 23.32±0.89 %, P<0.01) compared with littermate controls after TAC (n=8 each). In addition, Bsg+/- mice showed significantly less LV weight/body weight ratio (P<0.05) and lung weight/body weight ratio (P<0.01) compared with controls. Both MMP activities (in situ zymography by DQ gelatin) and oxidative stress (dihydroethidium staining) in loaded LV were less in Bsg+/- mice compared with controls. Bsg+/- mice were more likely to survive after TAC compared with Bsg+/+ mice, regardless of the source of bone marrow ( Bsg+/+ or Bsg+/- ), suggesting the crucial role of Bsg in cardiac tissues. Importantly, histological analysis showed that cardiac interstitial fibrosis was remarkably less in Bsg+/- mice compared with controls (5.08±1.23 vs. 12.25±1.17 %, P<0.01). Finally, we isolated cardiac fibroblasts (CFs) from Bsg+/+ and Bsg+/- mice, which were subjected to stimulation with angiotensin II (100nM) or cyclic mechanical stretch (+20%). Both stimuli significantly increased Bsg expression, secretion, and ERK/Akt activation in Bsg+/+ CFs, all of which were significantly less in Bsg+/- CFs (all P<0.05). Consistently, Bsg+/- CFs were significantly less proliferative compared with Bsg+/+ CFs.

Conclusions: These results indicate that Bsg plays a crucial role in the pressure-overload-induced cardiac hypertrophy, fibrosis and failure in mice.
Abstract 13209: Adenylyl Cyclase 6 Deletion Increases Mortality and Slows Atrio-Ventricular Conduction after Sustained Beta-Adrenergic Receptor Stimulation
Authors: Ngai Chin Lai, Tong Tang, Paul Lee, Tracy Guo, Meihua Gao, H. Kirk Hammond
Journal: Circulation (2010)

Background: Chronic isoproterenol (Iso) infusion and associated excessive cAMP production reduces left ventricle (LV) function. Using our previously generated AC6 deletion line (AC6KO), which has i...
May impairment of mucociliary clearance in COPD be reversible
Authors: Juliana Tiyaki Ito, Dionei Ramos, Fabiano Francisco Lima, Juliana Nicolino, Fernanda Maria Machado Rodrigues, Gabriel Faustino Santa Brígida, Renata Marques David, Rafaella Fagundes Xavier, Marceli Rocha Leite, Alessandra Choqueta Toledo, Ercy Mara Cipulo Ramos
Journal: European Respiratory Journal (2013)

Chronic Obstructive Pulmonary Disease (COPD) patients exhibit modifications in mucociliary clearance (MCC) that contribute to sputum production and airway inflammation, which predispose this population to recurrent infections. It9s known that ex-smokers with normal lung function may present MCC reversibility after smoking cessation, however in COPD ex-smokers it9s unknown. Aim: To evaluate and to compare the MCC of smokers, COPD smokers and COPD ex-smokers. Methods: We evaluated 112 subjects, divided in five groups: severe COPD (n=22), moderate COPD (n=20), COPD smokers (17), current smokers (n=27) and non-smokers (n=26). Severe and moderate COPD patients were ex-smokers (FEV1% = 37,8±6 and 61±7; 60±49,7 and 62±45 pack/years; duration of smoking cessation = 11±10 and 6,2±3,7 years; respectively). COPD smokers and current smokers were maintaining the habit (FEV1% = 48,7±16,8 and 90,7±7; 31±24,8 and 40±21 pack/years; respectively). Non-smokers with normal lung function were matched for age. We evaluated MCC by Saccharin Transit Time (STT) test. Tests were conducted between 8 and 9 AM within air temperature and relative humidity controlled. Statistical analyses were performed using Kruskal-Wallis test followed by Dunn’s test. Results: STT was higher in COPD smokers and current smokers compared to both groups of COPD ex-smokers and non-smokers (p=0,001). There was no difference in STT between severe and moderate COPD ex-smokers, and their values of STT were similar to non-smokers. Conclusion: COPD ex-smokers showed better MCC compared to current smokers and COPD smokers, also presented MCC similar to non-smokers. These results suggest that quitting smoking, even in people who developed COPD, leads to MCC9s reversibility.
Clinical Judgment and Treatment Options in Stable Multivessel Coronary Artery Disease
Authors: Alexandre C. Pereira, Neuza H.M. Lopes, Paulo R. Soares, Jose Eduardo Krieger, Sergio A. de Oliveira, Luiz A.M. Cesar, Jose A.F. Ramires, Whady Hueb
Journal: Journal of the American College of Cardiology (2006)
Tuberculosis in chronic kidney disease and dialysis patients in Birmingham
Authors: Jumaa Bwika, Lauren Bass, Alex Lewis, Martin Dedicoat, Jyoti Baharani, Heinke Kunst
Journal: European Respiratory Journal (2014)

Introduction   Birmingham has one of the highest tuberculosis (TB) rates, up to 90:100,000 {Pedrazzoli D, Health Protection Agency 2012} in UK. TB in chronic kidney disease (CKD) has an incidence between 6.9-52.5 times compared to the general population {Hussein, M.M Semin Dial, 2003}. There is insufficient data on TB in CKD in the U.K.   Methods   A retrospective study looking at the epidemiology and natural history of active TB in CKD between 2000 and 2010 in Birmingham, UK. We used Stata I/C©.   Results   54 patients were identified as summarised.  Extrathoracic TB is difficult to diagnose in CKD.  Overall, diagnosis was via microbiology in 24(44%) and histology in 8(15%). Treatment was well tolerated but we had 5(9%) deaths.   Conclusion   Extra-pulmonary TB is more common in CKD and diagnosis is difficult. We had a lower mortality compared to the literature.
Genuflecting to Hospital Variation in Home Discharge
Authors: Joseph A. Hyder
Journal: JAMA Surgery (2015)

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Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells
Authors: Min Lu, Lijuan Xia, Yen-Chun Liu, Tsivia Hochman, Laetizia Bizzari, Daniel Aruch, Jane Lew, Rona Weinberg, Judith D. Goldberg, Ronald Hoffman
Journal: Blood (2015)
Luteinizing hormone pulse characteristics in depressed women
Authors: W H Meller, K M Zander, R D Crosby, G E Tagatz
Journal: American Journal of Psychiatry (1997)

Objective: Luteinizing hormone (LH) pulse characteristics in depressed and normal women were compared to determine whether hypothalamic dysregulation in depression extends to the hypothalamic-pituitary-gonadal axis.Method: The subjects were 10 depressed and 13 normal comparison women admitted to a clinical research center.For each woman, an intravenous line was started and blood was withdrawn every 10 minutes for 8 hours.Blood samples were assayed for LH and LH pulse characteristics determined by using the computerized cluster algorithm of Veldhuis and Johnson.Results: The depressed women differed significantly from the comparison women in LH pulse amplitude, rhythmicity, and area under the curve.Conclusions: Major depressive disorder is associated with abnormal regulation of luteinizing hormone.Gonadotropin regulation may provide a hormonal link between major depressive disorder and impaired fertility.
International Conference on Capsule and Double-Balloon Endoscopy (ICCD)
Authors: M. Delvaux, G. Gay
Journal: Endoscopy (2011)

This review reports the highlights of the first International Conference on Capsule and Double-Balloon Endoscopy, held in Paris (27 - 28 August 2010), under the chairmanship of Professor G. Gay (Nancy, France). The conference was devoted to the technical issues and clinical experience related to capsule endoscopy and double-balloon endoscopy (DBE), techniques that have been developed over the past decade for the endoscopic investigation of intestinal diseases. The conference focused on the technical advances of new-generation endoscopes and capsules and the clinical experience gained with capsule endoscopy and DBE. Important advances in the knowledge of obscure gastrointestinal bleeding, inflammatory bowel diseases, and celiac disease were also discussed. The second part of the conference was mainly devoted to the investigation of the colon and discussed the technical issues and results of initial controlled studies of the colonic capsule vs. conventional colonoscopy. In addition, the clinical usefulness of double colonoscopy was demonstrated in patients with previously failed colonoscopy. Finally, the role of DBE was discussed with respect to the investigation and treatment of patients with surgically modified anatomy. The conference was attended by 750 delegates and presented a unique opportunity for an in-depth review of the current knowledge in the field and to ascertain/determine the main lines for the future developments of capsule endoscopy and DBE.
Prognosis of pneumocystis jirovecii pneumonia in non-HIV patients
Authors: Zehra Nur Töreyin, Pervin Ekren, Ayse Caner, Seray Töz, Alev Gürgün, Hatice Uluer, Feza Bacakoglu
Journal: European Respiratory Journal (2013)

Pneumocystis jirovecii pneumonia (PcP) is an opportunistic infection which can have different prognosis and progression among patients with HIV and non-HIV. It is still controversial whether Cytomegalovirus (CMV) co-infection worsens the prognosis or not. In this retrospective study, we aimed to investigate the effect of CMV co-infection in the prognosis of patients with PcP.

In the study 20 immunocompromised non-HIV PcP (median age 54.3±15.3 yrs, 13 males) patients who were admitted to our clinic from January 2009 to December 2012 were included. Demographic characteristics of the patients, immunosupressive therapy, anti-microbial prophylaxis, clinical, laboratory, radiological findings, the diagnostic method, the data for the presence and treatment of co-infection and respiratory failure were recorded.

On admission, 16 (80%) of the patients were on corticosteroid treatment. The median APACHE II Score was 19.0 (9-40), PaO2/FiO2 ratio was 147.5 (78-471). PcP diagnosis was made by microscopic examination in 2 cases and by PCR in 14 cases while in 4 cases both method was used. During follow-up, co-infection occured in 17 (85%) of the patients. 16 (80%) of them developed ARDS, 17 (85%) of the patients required invasive mechanical ventilation and 14 (70%) of them died. Mortality rates were higher in patients who developed ARDS, were intubated and co-infected (p=0.01, p=0.018, p=0.018, respectively). Twelwe (70.8%) of the patients had CMV co-infection. Progression to ARDS and intubation rates were higher (p=0.036 and p=0.049, respectively) in these patients.

In conclusion; among the non-HIV patients with PcP, progression to ARDS and mortality rates are higher in the presence of co-infection especially with CMV.
Abstract 21393: Nitric Oxide Regulates Pde5 Expression Through Its S-nitrosylation
Authors: Ping Zhang, Zhongbing Lu, Xin Xu, Yingjie Chen, Robert J Bache
Journal: Circulation (2010)

We recently have found that PDE5 protein expression is regulated by oxidative stress in the failing heart. Since increased superoxide anion can reduce nitric oxide bioavailability, the purpose of t...
Committees should devise special forms for the social sciences
Authors: B J Oddens, D De Wied
Journal: BMJ (1995)

EDITOR,--We welcome the recent editorial and papers on research ethics committees,1 2 3 4 which were published at the time when we were revising our ethical and scientific standards. Our organisation deals with questionnaire surveys relating to reproductive health carried out in various European and Asian countries. We are all too familiar with the problems recognised in the articles. In our view, many are related to the fact that, apart from general principles of scientific …