tbuckley/cabot-search huggingface dataset:
Reaction of the Adrenal Cortex to Physical and Emotional Stress in College Oarsmen
Authors: Albert E. Renold, T. B. Quigley, Harrison E. Kennard, George W. Thorn
Journal: New England Journal of Medicine (1951)

CHANGES in the level of circulating eosinophils after administration of adrenal cortical hormones, ACTH or epinephrine have been accepted as an index of adrenal cortical activity.1 Hormones elaborated by the adrenal cortex are known to be links in the physiologic response to stress. The eosinophil response to actual stress situations such as hypoglycemia, surgery, trauma and others2 3 4 has been described. The stress situations studied, however, have been as a rule abnormal and artificial.The Harvard–Yale four-mile boat race and the preceding two weeks of intensive training of crews presented an opportunity to study the response of healthy young men to . . .
Abstract 1658: Cell death and growth arrest pathways mediating the actions of stilbene 5c in HCT-116 colon cancer cells and B16F10 melanoma cells.
Authors: Moureq R. Alotaibi
Journal: Cancer Research (2013)

Abstract The stilbene derivative, cis-3, 4’, 5-trimethoxy-3’-aminostilbene (stilbene 5c), is a potentially potent antitumor agent that acts via binding to the colchicine-binding pocket in microtubules. Earlier studies have shown that stilbene 5c induces cell death in ovarian cancer cells and leukemic cells (Cao TM et al. Am J Hematol. 2008;83:390-7; Durrant D et al. Gynecol Oncol. 2008; 110:110-7).). The present study was designed to investigate the effectiveness of this microtubule poison against the HCT-116 human colon cancer cell line as well as B16F10 melanoma cells and its mechanisms of action. Time course studies demonstrated that stilbene 5c produces a decrease in cell viability in both cell lines. The capacity of the cells to proliferate was not restored upon removal of the drug after 5 days of exposure. Consistent with the results of the time course studies, β-galactosidase staining indicated that treatment with stilbene 5c also promotes senescence. In addition to senescence, HCT-116 cells and B16F10 melanoma cells treated with stilbene 5c displayed formation of autophagic vesicles by acridine orange staining, which was supported by fluorescence-activated cell sorting (FACS). Further evidence of autophagy was derived from treatment of HCT116 cells expressing an RFP-LC3 construct with stilbene 5c, in which LC3 puncta formation increased in a time-dependent manner. DAPI staining, TUNEL, and Annexin 5 staining indicated that apoptosis is also occurring in stilbene 5c-treated HCT-116 cells. Cell cycle analysis of HCT116 cells demonstrated growth arrest at both G1 and G2/M, and an increase in the subG1 population at days 3 and 5, which correspond to senescence and apoptosis respectively. Interestingly, DAPI and Hoechst staining of HCT116 cells revealed morphological changes in the cell nuclei (binucleated and micronucleated cells), which suggest that mitotic catastrophe may also serve as a mode of cell death after treatment with stilbene 5c. Our studies also indicated that stilbene 5c works in a p53-independent manner. p53-null HCT116 cells demonstrated similar sensitivity to stilbene as p53-wild type HCT116 cells. Consistent with previous studies in other experimental cancer models, this work indicates that stilbene 5c could potentially be effective against melanoma and colon cancer through the promotion of multiple modes of cell death. Citation Format: Moureq R. Alotaibi. Cell death and growth arrest pathways mediating the actions of stilbene 5c in HCT-116 colon cancer cells and B16F10 melanoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1658. doi:10.1158/1538-7445.AM2013-1658
Abstract LB-31: USP15 stabilizes the TGF-β receptor I and promotes oncogenesis through the activation of the TGF-β signal in glioblastoma
Authors: Pieter J. Eichhorn, Laura Rodon, Alba Gonzalez-Junca, Jose Baselga, Joan Seoane
Journal: Cancer Research (2012)

Abstract In advanced cancer including glioblastoma, the TGF-β pathway acts as an oncogenic factor and is considered a therapeutic target. Using a functional RNA-interference screen, we have identified the deubiquitinating enzyme USP15 as a critical component of the TGF-β signaling pathway. USP15 binds to the SMAD7-SMURF2 complex and deubiquitinates and stabilizes the TGF-β receptor I leading to an enhanced TGF-β signal. Importantly, we find that the USP15 gene is found amplified in glioblastoma, breast and ovarian cancer and that USP15 gene amplification confers poor prognosis in glioblastoma patients. Furthermore we demonstrate that downregulation or inhibition of USP15 in a patient-derived orthotopic mouse model of glioblastoma decreases TGF-β activity. Moreover, depletion of USP15 decreases the oncogenic capacity of patient-derived glioma-initiating cells due to the repression of TGF-β signaling. Our results show that USP15 regulates the TGF-β pathway and is a critical factor in glioblastoma pathogenesis. 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-31. doi:1538-7445.AM2012-LB-31
QL-18 * CLOSING THE GAP: BEREAVEMENT SUPPORT FOR FAMILIES, CAREGIVERS, AND MEDICAL STAFF
Authors: J. Lima, R. Cavaliere, E. Porensky
Journal: Neuro-Oncology (2014)

The National Comprehensive Cancer Network (NCCN) Guidelines® "are the first to include death as an expected outcome and after-death care for the family as an essential part of the continuum of cancer care". NCCN Guidelines® also include recommendations for bereavement support of health care providers themselves. Despite this, there is little consensus regarding the role of primary oncology practitioners in families' after-death bereavement care, and little attention is given to providers' own grief and bereavement needs. For patients' families, the neuro-oncology team is formalizing an approach to after-death care to include (a) an expression of condolence (e.g. sympathy card signed by clinic staff and primary oncologist), (b) referral to bereavement services (e.g. support group), (c) intermittent telephone calls over a one-year period, and (d) optional debriefing meetings. We are also proposing a "Service of Remembrance" to be held during the month of May to coincide with "Brain Tumor Awareness Month". This will be a time for reflection and remembrance to honor those who have died, not only for families and caretaker(s) but also for staff who were involved in the care of their loved ones. For healthcare providers, participation in monthly "Schwartz Center Rounds®" is encouraged. The Schwartz Center Rounds® are part of a national program which utilizes an open forum to discuss difficult social and emotional issues related to patient care. Current challenges to implementation of a comprehensive after-death bereavement program for families and staff include lack of time, ambiguity as to which individuals are performing proposed family follow up, and a paucity of research to guide intervention implementation. Future directions include survey of the bereavement needs and preferences of our population, a process to identify at risk health professionals for complicated bereavement, moral distress or compassion fatigue, and a systematic approach to address these issues.
THU0242 Effect of Genetic Variants in Proteins of the Folic Acid Metabolic Pathways in the Toxicity of Methotrexate
Authors: I. Gonzalez-Alvaro, A. Lamana, A. M. Ortiz, R. Garcia-Vicuña
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The study of genetic variants of enzymes in the metabolic pathways of folic acid has provided conflicting results regarding toxicity or clinical response to methotrexate (MTX). There are several reasons for this lack of reproducibility: the origin of populations studied, differences in the definition of non-responder or presence of toxicity, as well as prejudice either in patients or physician which can bias the decision to discontinue MTX. <h3>Objectives</h3> To analyze the effect of functional genetic variants of methylen-tetrahydrofolate reductase (MTHFR; rs1801131 y rs1801133), the membrane transporter ABCB1 (rs1045642), the AICAR transformylase/IMP ciclohydrolase (ATIC; rs2372536) and folil polyglutamate synthetase (FPGS; rs1544105) on GPT/ALT, leukocytes, platelets and hemoglobin (Hb) levels in patients with early arthritis (EA) exposed to MTX. <h3>Methods</h3> We analyzed a total of 1034 visits (511 with MTX, 523 without MTX) from 287 patients (77% female; median age at disease onset: 54 years [interquartile range: 43 – 67]) of our EA register. Sociodemographic, clinical, laboratory and therapeutic data were systematically collected at baseline, 6, 12, 24 and 60 months. SNP genotyping was performed through specific TaqMan probes (Applyed Biosystem). We performed a multivariate analysis for each of the four dependent variables (GPT/ALT, leukocytes, platelets and Hb) through generalized linear models using the "glm" command of Stata12. The statistical significance was set at p&lt;0.0125 due to multiple comparisons. However, all those variables with p&lt;0.15 were maintained in the multivariable models. <h3>Results</h3> The table shows results of the statistical analysis when MTX was used: <h3>Conclusions</h3> Our data suggest that genetic variants of MTHFR and ABCB1 for hepatotoxicity and FGPS for haematologic toxicity may be more important than other factors such as MTX dose, age and renal function, although there is probably an indication bias with these two later variables. <h3>Disclosure of Interest</h3> None Declared
Even “Bigger Gods” developed amongst the pastoralist followers of Moses and Mohammed: Consistent with uncertainty and disadvantage, but not prosocality
Authors: Edward Dutton, Guy Madison
Journal: Behavioral and Brain Sciences (2016)

Abstract The gods of monotheistic religions, which began amongst pastoralists and defeated exiles, are closer to Big Gods than those associated with ancient city-based polities. The development of Big Gods is contingent upon a need to reduce uncertainty and negative feelings in combination with a relatively high level of prosociality, rather than a need to induce or assess prosociality.
Biliary Excretion of Tc-99m EC in Renal Studies
Authors: SAAD ZAKKO, LUBAN MRHAC, JAMILA AL-BAHRI, HANAN AL-SHAMSI, SALHA LOOTAH, RAYJANAH BENJAMIN
Journal: Clinical Nuclear Medicine (1998)

The role of biliary excretion in Tc-99m ethylenedicysteine (EC) renal imaging was studied. Of 2,215 dynamic renal studies performed with Tc-99m EC, only nine cases of gallbladder visualizations and/or biliary excretion were identified. In no case did biliary excretion affect the interpretation of the renal study.
Abstract 2745: INK128, a TORC1/2 kinase inhibitor, enhances the efficacy of cytotoxic therapies in endometrial tumor models
Authors: Linda Kessler, Katti Jessen, Matthew Janes, Jocelyn Staunton, Jeff Kucharski, Xin Guo, Marikka Elia, Urmi Banerjee, Lucy Lan, Shunyou Wang, Josh Stewart, Angelina Luzader, Levan Darjania, Liansheng Li, Katrina Chan, Michael Martin, Pingda Ren, Christian Rommel, Yi Liu
Journal: Cancer Research (2012)

Abstract Background: The mammalian target of rapamycin (mTOR), which comprises two protein complexes, TORC1 and TORC2, regulates tumor cell growth, metabolism and motility. In endometrial cancer, the mTOR pathway is aberrantly activated by constitutive mitogen stimuli, such as FGFR2 and multiple genetic mutations such as PIK3CA, PIK3R1/2, PTEN and LKB1. The activation of multiple signaling pathways, cross-feedback and redundancy of these pathways led us to explore the combination of mTOR kinase inhibitor with chemotherapeutic agents for achieving maximal efficacy in preclinical mouse models of endometrial cancer. Results: INK128 is a potent and selective TORC1/2 inhibitor with excellent drug-like properties currently advancing in clinical development. INK128 inhibits endometrial tumor cell proliferation in vitro and displays tumor growth inhibition in endometrial tumor models. In most instances, the anti-tumor activity of INK128 is cytostatic compared to the cytotoxic effect of taxol and carboplatin. In endometrial tumor cells of diverse genetic backgrounds, combining INK128 with taxol resulted in a synergistic inhibition of tumor cell proliferation, sustained suppression of PI3K/AKT/mTOR pathway activity, skewed cell cycle and an increase in apoptosis. INK128 decreased the expression of anti-apoptotic protein MCL-1 and therefore mechanistically enhanced taxol-triggered apoptosis. In endometrial mouse tumor models with PTEN and FGFR2 mutations, the combination induced marked tumor regression and significantly delayed tumor re-growth upon discontinuation of the treatment compared to taxol treatment alone. The combination therapy was well-tolerated and the enhanced anti-tumor efficacy correlated with mechanism-based inhibition of several TORC1 and TORC2 pharmacodynamic markers and induction of apoptosis in vivo. Additionally, combining INK128 with taxol or carbotaxol resulted in tumor regression in taxol-resistant endometrial tumor models. The opportunity of optimizing dose and schedule combination regimens as well as biomarkers predicting sensitivity/resistance to INK128/taxol combination will be discussed. Conclusion: The combination of mTOR kinase inhibitors with chemotherapeutic agents is a compelling strategy to improve therapeutic outcome and to overcome chemo-resistance for tumor types with aberrant activation of the PI3K/mTOR pathway such as endometrial cancer. 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 2745. doi:1538-7445.AM2012-2745
Abstract 4121: Hyaluronan promotes Rho kinase and PI-3 kinase signaling in head and neck cancer
Authors: Steven J. Wang, Carlos Torre, Weiliang Xia, Lilly YW Bourguignon
Journal: Cancer Research (2010)

Abstract Objectives: Hyaluronan (HA) is a ligand for the transmembrane receptor CD44, which acts through multiple signaling pathways to influence cellular behavior. The objective of this study was to investigate whether HA and CD44 promote Rho kinase and phosphatidyl inositol-3 (PI-3) kinase mediated oncogenic signaling to alter cisplatin sensitivity and stimulate tumor cell proliferation, migration, and matrix metalloproteinase (MMP) secretion in head and neck squamous cell carcinoma (HNSCC). Design/Subjects: Laboratory investigation utilizing a HNSCC cell line, HSC-3. Interventions: Rho kinase and PI-3 kinase activity, myosin phosphatase and AKT phosphorylation, tumor cell growth, migration, and MMP secretion were measured in the presence or absence of HA, cisplatin, and inhibitors of Rho kinase and PI-3 kinase. Results: The addition of HA, but not HA plus anti-CD44 antibody, resulted in increased Rho kinase and PI-3 kinase activity. Immunoblotting studies demonstrated that HA promotes Rho kinase mediated myosin phosphatase phosphorylation and PI-3 kinase mediated AKT phosphorylation. HA was shown to promote migration and increased MMP secretion through Rho kinase mediated signaling. HA treatment promoted increased tumor proliferation and resulted in a 12-fold reduced ability of cisplatin to cause HNSCC cell death. On the other hand, the presence of Y-27632, a Rho kinase inhibitor, and LY-294002, a PI-3 kinase inhibitor, blocked HA-mediated cisplatin resistance. Conclusions: Our results suggest that HA and CD44 promote Rho kinase and PI-3 kinase mediated oncogenic signaling and cisplatin resistance. Perturbation of HA-CD44 mediated Rho kinase and PI-3 kinase signaling pathways may be a novel strategy to treat HNSCC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4121.
P879 CIRCULATING miRNA-122/let-7d RATIO, HEPATITIS C VIRUS LOAD AND FIBROSING CHOLESTATIC HCV RECURRENCE AFTER LIVER TRANSPLANTATION
Authors: A. Finkenstedt, S. Lechner, N. Baumgartner, J. Pratschke, I. Graziadei, W. Vogel, H. Zoller
Journal: Journal of Hepatology (2014)
BMA calls for lower blood alcohollevel for drivers Number of GPs increases Public health doctors forecast required manpower New health minister appointed Government promises extra pounds sterling50m for mentally ill patients GPs clarify their role in childbirth
Authors: L. Beecham
Journal: BMJ (1995)

# BMA calls for lower blood alcohollevel for drivers {#article-title-2}

The BMA and the Parliamentary Advisory Council for Transport Safety (PACTS) are calling for the legal blood alcohol limit for driving to be reduced to 10.9 mmol/l (50mg/100ml) from the current level of 17.4 mmol/l (80mg/100ml). Research has shown that the risk of becoming involved in a traffic accident greatly increases at blood alcohol levels over 50mg/100ml and the two organisations want legislation to be introduced to reflect this evidence. Some other European countries have switched to the lower level; France is the latest country to do this. In a letter to the transport secretary, Sir George Young, the BMA and PACTS say that legislation needs to be enforced if it is to be effective and that they would support measures to enhance current levels of enforcement, in particular the introduction of random breath testing. The possibility of being tested randomly is considered more likely to act as a deterrent as there is a higher chance of drivers being caught.

# Number of GPs increases {#article-title-3}

The number of general practitioners in England and Wales increased by 0.7% from 30416 to 30615 during the past year, with women accounting for the majority of the increase. In April 1995, 29.9% of all general practitioners were women. The average patient list size fell to 1869, compared with 2059 in 1985. The number of general practitioner registrars decreased by 3.6% between April 1994 and April 1995 (from 1611 to 1503), but the number of women registrars increased by 1.6% so that more than half of all registrars …
P422Cardiac ischemic stress during remote ischemic preconditioning
Authors: S Abdul Ghani, GD Angelini, MS Suleiman
Journal: Cardiovascular Research (2014)

Background: Remote ischemic preconditioning (RIPC) induced by brief ischemia/reperfusion (I/R) cycles of remote organ (e.g. limb) is cardio-protective. The myocardial cellular changes during RIPC that are responsible for this phenomenon are not currently known. However, it is widely accepted that unlike classical ischemic preconditioning, RIPC does not induce ischemic stress in the myocardium. To address this issue we developed a novel RIPC mouse model and monitored myocardial changes in energy-rich phosphates.
COMPLICACIONES RELACIONADAS CON LA CPRE: ANÁLISIS PROSPECTIVO DE FACTORES ASOCIADOS EN 1607 PROCEDIMIENTOS
Authors: A Domínguez, J Espinel, R Diez, G Rascarachi, S Vivas
Journal: Endoscopy (2010)

Objetivo: Determinar la incidencia y los factores asociados a presentar complicaciones postCPRE en nuestro centro.
P695Anti-leakage mechanism and effect of sodium aescinate on the permeability of blood-brain barrier exposed to hypoxia rat
Authors: Q Zhou
Journal: Cardiovascular Research (2014)

Objective: To study the anti-leakage mechanism and protective effect of sodium aescinate on the blood-brain barrier of rat exposed to hypoxia. Methods 75 SD rats were randomly divided into normoxic control (NC),simple hypoxic (SH) and drug treated (DT) group. Acute brain edema rat model was established by a simulation of plateau acute hypoxia for 5 days. Dry-wet method to determine cerebral water content, evans blue (EB) method to evaluate the permeability of blood-brain barrier (BBB). HE staining to detect pathological changes of brain. Lanthanum nitrate tracer method with transmission electron microscopy (TEM) to observe the state of BBB tight junction (TJ) and ultrastructure of brain tissue. Protein and mRNA expression of Occludin, Zo-1 and Claudin-5 were investigated by immunohistochemistry, western-blotting and real-time PCR respectively. Results After exposure to acute hypoxia for 5 days, compared with NC group, the water content of brain in SH group increased obviously (P<0.01) while that in DT group decreased significantly (P<0.05), and EB content analysis revealed a similar result. It was observed by microscopy that hippocampus neurons were lost and edemas occurred heavily in SH group while slightly in DT group. It was detected by TEM that lanthanum nitrate infiltrated and deposited into cerebral interstitium through widened TJ gap of the brain microvascular endothelial cells (BMVECs), and the perivascular edema was obvious in SH group, while these changes were lessened in DT group. The lowest expression levels of Occludin mRNA and protein were found in SH group (P<0.01), and the highest levels were in DT group (P<0.05). Meanwhile, to compare with SH group, the expression of zo-1 and Claudin-5 mRNA increased remarkably in both NC and DT group (P<0.05), while no significant difference existed between the latter two groups. Conclusion Acute hypoxia exposure may lead to a remarkable decline of brain occludin protein and the Occludin, Zo-1 and Claudin-5 mRNA, and an obvious increase of BBB permeability. Sodium aescinate can up-regulate the expression level of these molecules and decrease BBB permeability,thus play a role of anti-leakage and BBB protection.