tbuckley/cabot-search huggingface dataset:
Stimulation of angiogenesis by adenosine on the chick chorioallantoic membrane.
Authors: J W Dusseau, P M Hutchins, D S Malbasa
Journal: Circulation Research (1986)

The effect of adenosine on the vascular density of the chick chorioallantoic membrane was studied. Elvax polymer pellets containing 0.2-3.0 mg of adenosine were placed on the chorioallantoic membrane of 10-day embryos. Control pellets containing mannitol were placed at least 1 cm away. After 4 days the membrane was formalin-fixed and removed. A thin plastic coverslip, inscribed with concentric circles (4-8 mm in diameter), was placed over the pellet. A vascular density index was estimated at 20 X by counting the number of intercepts between vessels and the inscribed circles. Adenosine stimulated a dose-dependent increase (p less than 0.01) in the vascular density index with the 3-mg pellets inducing a 15% increase. Inosine, a major metabolite of adenosine, did not cause a change in the number of intercepts counted. The adenosine-stimulated increase in vascularity was blocked with 110 micrograms of methyl-isobutyl-xanthine injected daily into the albumin. Partial inhibition was observed with 55 micrograms/day. Methyl-isobutyl-xanthine by itself did not affect the vascular density index. Dipyridamole enhanced adenosine's stimulation of vascular growth an additional 52%. Given alone, however, it had no effect on the membrane's vascularity. These data support an angiogenic role for adenosine. The modest, but consistent, increase in the vascular density index stimulated by adenosine, and the fact that it may be released during tissue hypoxia, is consistent with an hypothesis that this nucleoside plays a modulatory role in vessel proliferation accompanying conditions of long-term hypoxia.
Abstract 1938: Inhibition of both physiological and aberrant Wnt/β-catenin signaling activities associated with stemness in nasopharyngeal carcinoma
Authors: Yue Cheng, Yee Peng Phoon, Maria L. Lung
Journal: Cancer Research (2014)

Abstract We previously demonstrated that basic or physiological levels of β-catenin signaling and tissue context play decisional roles in the regulation of self-renewal networks in nasopharyngeal carcinoma (NPC) HONE1 cells. Introduction of physiological levels of β-catenin signaling in HONE1 hybrid cells plays a central role in the control of other pathway activities, such as TGF-β, Activin, and pluripotency maintenance (LIFR and IL6ST), during the stemness transition process. These results revealed novel regulatory relationships among Wnt signaling, stemness, epithelial-mesenchymal transition (EMT), tumor suppressive pathways and expression of common cancer stem cell surface markers, such as CD44 and CD133, in human tumor cells. In current studies, we found that several NPC cell lines, including CNE1, HK1, HNE1, SUNE1, and C666-1, have aberrant and significant up-regulation of β-catenin expression, when compared to HONE1 cells that have low levels endogenous β-catenin expression. In these NPC cells with aberrant β-catenin signaling activities, the Wnt pathway (Axin2, APC, TCF1 and TCF3), stemness factors (Nanog, and Oct4) and pluripotency markers (IFITM1 and GRB7) are strongly overexpressed, compared to HONE1 cells. Our findings suggest that aberrant Wnt/β-catenin signaling activities may play a prominent role in promoting tumor progression in NPC cells. To further verify the role of aberrant β-catenin signaling in NPC, we utilize shRNA to knock down β-catenin expression in these cells, including CNE1 and HK1. As found in HONE1 hybrids, the diminished expression of core stem cell factors (Nanog, Oct4, Klf4, and Sox2) is also detected in both CNE1 and HK1 cell lines. Concomitantly, the gene expression of EMT markers (E-cadherin and Zeb1) is also inhibited when β-catenin is knocked down by shRNA β-catenin infection. These preliminary results suggest that β-catenin signaling plays a dominant role in regulating both physiological and aberrant Wnt/β-catenin signaling activities as well as EMT events in NPC development. Citation Format: Yue Cheng, Yee Peng Phoon, Maria L. Lung. Inhibition of both physiological and aberrant Wnt/β-catenin signaling activities associated with stemness in nasopharyngeal carcinoma. [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 1938. doi:10.1158/1538-7445.AM2014-1938
Common Variants in Myocardial Ion Channel Genes Modify the QT Interval in the General Population
Authors: Arne Pfeufer, Shapour Jalilzadeh, Siegfried Perz, Jakob C. Mueller, Martin Hinterseer, Thomas Illig, Mahmut Akyol, Cornelia Huth, Andreas Schöpfer-Wendels, Bernhard Kuch, Gerhard Steinbeck, Rolf Holle, Michael Näbauer, H. -Erich Wichmann, Thomas Meitinger, Stefan Kääb
Journal: Circulation Research (2005)

Altered myocardial repolarization is one of the important substrates of ventricular tachycardia and fibrillation. The influence of rare gene variants on repolarization is evident in familial long QT syndrome. To investigate the influence of common gene variants on the QT interval we performed a linkage disequilibrium based SNP association study of four candidate genes. Using a two-step design we analyzed 174 SNPs from the KCNQ1, KCNH2, KCNE1, and KCNE2 genes in 689 individuals from the population-based KORA study and 14 SNPs with results suggestive of association in a confirmatory sample of 3277 individuals from the same survey. We detected association to a gene variant in intron 1 of the KCNQ1 gene (rs757092, +1.7 ms/allele, P =0.0002) and observed weaker association to a variant upstream of the KCNE1 gene (rs727957, +1.2 ms/allele, P =0.0051). In addition we detected association to two SNPs in the KCNH2 gene, the previously described K897T variant (rs1805123, −1.9 ms/allele, P =0.0006) and a gene variant that tags a different haplotype in the same block (rs3815459, +1.7 ms/allele, P =0.0004). The analysis of additive effects by an allelic score explained a 10.5 ms difference in corrected QT interval length between extreme score groups and 0.95% of trait variance ( P &lt;0.00005). These results confirm previous heritability studies indicating that repolarization is a complex trait with a significant heritable component and demonstrate that high-resolution SNP-mapping in large population samples can detect and fine map quantitative trait loci even if locus specific heritabilities are small.
Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial
Authors: Evan A Stein, Dan Gipe, Jean Bergeron, Daniel Gaudet, Robert Weiss, Robert Dufour, Richard Wu, Robert Pordy
Journal: The Lancet (2012)
Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8+ T Cells Ex Vivo
Authors: Weijuan Gong, Mingchun Ji, Zhengfeng Cao, Liheng Wang, Yayun Qian, Maozhi Hu, Li Qian, Xingyuan Pan
Journal: Cellular and Molecular Immunology (2008)
Identifying Biological and Clinical Characteristics of Patients with Gastrointestinal Stromal Tumours (Gist) Responding to Imatinib Therapy for More Than 5 and 10 Years
Authors: J. Bosma, M. Verboom, I. Gataa, E.V. Werkhoven, H. Gelderblom, R.H.J. Mathijssen, A.K.L. Reyners, C. Osuch, J.A. Siedlecki, K. Kubackova, I. Kocakova, E. Bylina, A. Le Cesne, P. Rutkowski, N. Steeghs
Journal: Annals of Oncology (2014)
Ecological and constructivist approaches and the influence of illusions
Authors: Denise D. J. de Grave, Jeroen B. J. Smeets, Eli Brenner
Journal: Behavioral and Brain Sciences (2002)

Norman tries to link the ecological and constructivist approaches to the dorsal and ventral pathways of the visual system. Such a link implies that the distinction is not only one of approach, but that different issues are studied. Norman identifies these issues as perception and action. The influence of contextual illusions is critical for Norman's arguments. We point out that fast (dorsal) actions can be fooled by contextual illusions while (ventral) perceptual judgements can be insensitive to them. We conclude that both approaches can, in principle, be used to study visual information processing in both pathways.
Slower heterosexual spread of HIV-2 than HIV-1
Authors: P.J. Kanki, K.U. Travers, R.G. Marlink, M.E. Essex, S. MBoup, A. Gueye-NDiaye, T. Siby, I. Thior, J-L. Sankalé, C-C. Hsieh, M. Hernandez-Avila, I. NDoye
Journal: The Lancet (1994)
Effects of Light and Food Schedules on Liver and Tumor Molecular Clocks in Mice
Authors: E. Filipski, P. F. Innominato, M. Wu, X.-M. Li, S. Iacobelli, L.-J. Xian, F. Levi
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Disrupted circadian coordination accelerates malignant growth, but the molecular mechanism is unclear. Methods: Healthy or Glasgow osteosarcoma–bearing mice (n = 162) were synchronized with light and darkness over 2–3 weeks, submitted to an 8-hour advance onset of light every 2 days (chronic jet lag) to disrupt circadian coordination, or submitted to chronic jet lag and meal timing to prevent molecular clock alteration. The expression of molecular clock genes and of the cell cycle genes c-Myc and p53 in liver and tumor was determined with quantitative reverse transcription–polymerase chain reaction at six circadian times over a 24-hour period of light and darkness and analyzed with analysis of variance and cosinor. Tumor weight was measured daily over the course of the experiment. All statistical tests were two-sided. Results: In synchronized mice, mean mRNA levels of clock genes Rev-erbα, Per2, and Bmal1 varied by 206-, four-, and 26-fold, respectively, over the 24 hours in healthy mouse liver; by 36-, 35-, and 32-fold in the livers of tumor-bearing mice; and by 9.4-, 5.5-, and sixfold in tumor tissue ( P = .046 to <.001). In mice subjected to chronic jet lag, the periodic changes were dampened and the clock gene rhythms were temporally shifted in liver and ablated in tumor, and tumor growth was accelerated. Meal timing reversed the chronic jet lag–induced alterations in Rev-erbα and Per2 expression in liver and of all three clock genes in tumor and slowed tumor growth. Tumor growth differed as a function of light and feeding schedules ( P = .04). No obvious rhythm was detected for p53 or c-Myc in liver or tumor tissues of synchronized mice. In healthy mice subjected to chronic jet lag, the mean level of p53 expression was cut in half ( P = .002), and a 12-fold circadian variation in c-Myc mRNA level ( P = .03) was induced in the liver of healthy mice, whereas complex expression patterns were found in the liver and tumor of tumor-bearing mice. Conclusions: Altered light–dark or feeding schedules modified the expression of molecular clock genes and genes involved in carcinogenesis and tumor progression.
A life threatening complication after ingestion of sodium phosphate bowel preparation
Authors: Y Mun Woo, Susan Crail, Graham Curry, Colin C Geddes
Journal: BMJ (2006)

<h3>Background</h3> Cancer vaccines are a promising strategy for cancer immunotherapy. Cancer vaccines elicits a specific cytotoxic immune response to tumor antigens. However, the efficacy of traditional peptide-based cancer vaccines is limited due to the inefficient delivery of antigens and adjuvants to dendritic cells (DCs). Therefore, it is necessary to develop a novel rationally designed cancer vaccine to maximize its desired effects. <h3>Methods</h3> A Self-assembling Vehicle-free Multi-component Antitumor nanoVaccine (SVMAV) was constructed by using an unsaturated fatty acid docosahexaenoic acid (DHA)-conjugated antigen and R848 (a Toll-like receptor 7/8 agonist) to encapsulate stattic (a signal transducer and activator of transcription 3 inhibitor). The characteristics of SVMAV were investigated. The ability of SVMAV to promote DC functions was examined by in vitro analysis. The antitumor effects of SVMAV and its combination with antiprogrammed cell death protein 1 antibody (aPD-1) were also investigated in vivo. The potential application of SVMAV for neoantigen-targeted, personalized cancer vaccines was examined in an orthotopic hepatocellular carcinoma model. <h3>Results</h3> The obtained SVMAV efficiently migrated into lymph nodes and primed CD8<sup>+</sup> T cells for exert neoantigen-specific killing by promoting the antigen uptake by DCs, stimulating DC maturation, and enhancing antigen cross-presentation, due to the simultaneous delivery of the antigen, R848 and stattic. SVMAV could not only yield a robust antitumor effect for primary melanoma allografts, but also exert a protective effect for lung metastases. Moreover, combination treatment of SVMAV and aPD-1 exerted synergistic antitumor activity and extended the survival duration of melanoma-bearing mice. Notably, a cell line-specific neoantigen-based SVMAV was designed according to predicted neoantigens for Hepa1-6 cells to examine the potential application of SVMAV for personalized cancer vaccine. Encouragingly, neoantigen-specific SVMAV achieved stronger antitumor activity than aPD-1 in an orthotopic hepatocellular cancer model established with Hepa1-6 cells. <h3>Conclusions</h3> In summary, this study offers an efficient codelivery platform for neoantigens and immunoregulatory compounds to enhance immune responses during cancer immune therapy.
Effects of exercise intensity on lymphocyte H<sub>2</sub>O<sub>2</sub>production and antioxidant defences in soccer players
Authors: A Sureda, M D Ferrer, P Tauler, D Romaguera, F Drobnic, P Pujol, J A Tur, A Pons
Journal: British Journal of Sports Medicine (2007)

Objective: Physical exercise is capable of enhancing or suppressing the immune response depending on the intensity and duration of exercise. This study investigated how exercise intensity influences the lymphocyte antioxidant response and the induction of cellular oxidative damage. Design: Eighteen voluntary male pre-professional soccer players participated in this study. Sportsmen played a 60 min training match, and were divided into three groups depending on the intensity degree during the match: low, medium and high intensities. Measurements: Malondialdehyde (MDA), vitamins C and E and haem oxygenase-1 (HO-1) gene expression were measured in lymphocytes. Reactive oxygen species (ROS) production was determined in lymphocytes and neutrophils. Results: Lymphocyte MDA levels and H 2 O 2 production were significantly increased in the group which performed the most intense exercise. Neutrophil counts and ROS production increased progressively with the exercise intensity. Vitamin C significantly decreased after exercise in the highest-intensity group in comparison with initial values, whereas vitamin E levels significantly increased in the medium and high-intensity groups. HO-1 gene expression significantly increased in the medium and high-intensity groups. Conclusions: Exercise intensity affects the lymphocyte and neutrophil oxidant/antioxidant balance, but only exercise of high intensity induces lymphocyte oxidative damage.
Human Papillomavirus Type 16 and <b> <i>TP53</i> </b> Mutation in Oral Cancer
Authors: Min Dai, Gary M. Clifford, Florence le Calvez, Xavier Castellsagué, Peter J. F. Snijders, Michael Pawlita, Rolando Herrero, Pierre Hainaut, Silvia Franceschi
Journal: Cancer Research (2004)

Abstract TP53 mutations were analyzed in 35 human papillomavirus (HPV) type 16 DNA-positive cancers of the oral cavity and oropharynx and in 35 HPV DNA-negative cancers matched by subsite, country, sex, age, and tobacco and alcohol consumption. Wild-type TP53 was found more frequently in cancer specimens that contained HPV16 DNA than in those that did not. All 14 HPV16 DNA-positive cancers in HPV16 E6 antibody-positive patients contained wild-type TP53, compared with 50% of corresponding HPV DNA-negative cancers (matched odds ratio, ∞; 95% confidence interval, 1.4–∞). In contrast, for HPV16 DNA-positive cancers in E6-negative patients, wild-type TP53 frequency was similar to that in corresponding HPV DNA-negative cancers (matched odds ratio, 1.0; 95% confidence interval, 0.2–5.4). TP53 inactivation is a major mechanism of HPV-related carcinogenesis in the oral cavity and oropharynx. The role of HPV in cancers also containing TP53 mutations remains to be clarified.
Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial
Authors: Michael G Kaplitt, Andrew Feigin, Chengke Tang, Helen L Fitzsimons, Paul Mattis, Patricia A Lawlor, Ross J Bland, Deborah Young, Kristin Strybing, David Eidelberg, Matthew J During
Journal: The Lancet (2007)
Achieving Sufficient Accrual to Address the Primary Endpoint in Phase III Clinical Trials from U.S. Cooperative Oncology Groups
Authors: Anneke T. Schroen, Gina R. Petroni, Hongkun Wang, Monika J. Thielen, Robert Gray, Jacqueline Benedetti, Xiaofei F. Wang, Daniel J. Sargent, Donald L. Wickerham, Walter Cronin, Benjamin Djulbegovic, Craig L. Slingluff
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Assessing impact of poor accrual on premature trial closure requires a relevant metric. We propose defining accrual sufficiency on apparent ability to address primary endpoints (PE) rather than attaining accrual targets. Experimental Design: All phase III trials open January 1, 1993, to December 31, 2002, by five U.S. oncology Clinical Trials Cooperative Groups (CTCG) were evaluated for accrual sufficiency and scientific results. Sufficient accrual included meeting accrual target, CTCGs documentation attesting adequate accrual, or conclusive results at interim analysis; insufficient accrual included poor accrual as cited closure reason or other reasons rendering a trial unable to address its primary endpoints. Closure rates based on our accrual sufficiency definition are compared with rates of meeting accrual targets and addressing the primary endpoints. A percentage of target accrual above which trials commonly answer the intended scientific question was identified to serve as an alternative to meeting full target accrual in designating accrual success. Results: Of 238 eligible trials, 158 (66%) closed with sufficient accrual. Among 80 trials with insufficient accrual, 70 (29%) closed specifically because of poor accrual. Inadequate accrual rates are overemphasized when defining accrual success solely by meeting accrual targets. Nearly 75% of trials conclusively addressed the primary endpoints with positive results in 39% of trials. Exceeding 80% of target accrual serves as a reliable proxy for answering the intended scientific question. Conclusions: Approximately one third of phase III trials closed with insufficient accrual to address the primary endpoints, primarily due to poor accrual. Defining accrual sufficiency broader than meeting accrual targets represents a fairer account of trial closures. Clin Cancer Res; 18(1); 256–62. ©2011 AACR.
Clinical Lecture on the Treatment of Wounds without Dressings, on Sutures and Acupressure
Authors: G. M. Humphry
Journal: BMJ (1867)

THERE is, perhaps, no branch of our art which presents greater oppor- tunities for good than the treatment of wounds, as there is probably none in which greater mischief has been conceived and executed-none in which meddlesomeness has proved so pemicious.Read, and you will be appalled at, the horrible accounts of the barbarisms practised by our forefathers with their setons, tents, and irritating unguents, which they thought fit to cram into every wound; the practice being based, as many bad practices are, upon monstrous and absurd theories.Truly, the present generation of surgeons have a hard task to make amends for the evils done by their predecessors; and let them not be too sure that they are not perpetuating some of those evils.Let us not be content to rest under the stigma of that question which, unfortunately, is more often asked than satisfactorily answered-" Do you ever see the wounds after amputation, removal of tumours, and other large operations, heal up by first intention ?"The very possibility of such a questioni is ani opprobrium to which we ought not tamely to submit ; especially as there can be little doubt that, if they were properly treated, these wounds, in the majority of cases, would heal at once.I beg you, then, not to rest satisfied with the present modes of treatment, and urge you to use your best efforts to improve them, and, at any rate, to give a careful consi- deration to the suggestions for better management of wounds -tvhich .mayfrom time to time be made.Do not despise small hints; for good surgery has much dependence upon attention to little matters.
Effect of Bolus Milrinone on Hemodynamic Variables and Pulmonary Vascular Resistance in Patients With Severe Left Ventricular Dysfunction: A Rapid Test for Reversibility of Pulmonary Hypertension
Authors: Michael M. Givertz, Joshua M. Hare, Evan Loh, Diane F. Gauthier, Wilson S. Colucci
Journal: Journal of the American College of Cardiology (1996)

To examine the feasibility of using milrinone to test pulmonary vascular reactivity in patients before heart transplantation, we tested the hypothesis that milrinone would lower pulmonary vascular resistance (PVR) in patients with severe heart failure. Fixed pulmonary hypertension is a risk factor for right heart failure and death after orthotopic heart transplantation. Sodium nitroprusside, the agent used most commonly to test for reversibility of pulmonary hypertension before transplantation, requires dose titration and is frequently limited by hypotension. Milrinone is an intravenously active phosphodiesterase inhibitor that acts rapidly and exerts both positive inotropic and direct vasodilator effects in patients with heart failure. The ability of milrinone to lower PVR in patients with heart failure has not been tested. In 27 patients with New York Heart Association functional class III or IV heart failure referred for heart transplantation with a PVR ≥ 200 dynes-s-cm−5, we measured the hemodynamic response to a single intravenous bolus of milrinone (50 μg/kg body weight) infused over 1 min. Milrinone decreased PVR in all patients. The effect was maximal 5 to 10 min after the bolus and persisted for at least 20 min. The reduction in PVR at 5 min ([mean ± SEM] 31 ± 4%) was associated with a 42 ± 4% increase in cardiac output and decreases of 12 ± 4% and 16 ± 5% in mean pulmonary artery and pulmonary artery wedge pressures, respectively, but no change in transpulmonary pressure gradient. Milrinone had no effect on heart rate or systemic arterial pressure. The magnitude of the decrease in PVR correlated inversely with the milrinone-induced increase in cardiac output. Bolus milrinone consistently decreases PVR in patients with pulmonary hypertension secondary to severe heart failure. This effect is rapid in onset and well tolerated, even by patients with low systemic arterial pressure. An intravenous bolus of milrinone can be used to test for the reversibility of pulmonary hypertension in patients with heart failure undergoing evaluation for heart transplantation.