tbuckley/cabot-search huggingface dataset:
Abstract 5400: Exercise activates AMP-activated protein kinase in breast cancer cells.
Authors: Grith W. Højfeldt, Christine Dethlefsen, Bente K. Pedersen, Pernille Hojman
Journal: Cancer Research (2013)

Abstract Objective: Cancer cells are characterized by a changed cellular metabolism, favoring glycolysis. AMPK, a serine/threonine kinase regulates cellular metabolism, and induces fatty acid oxidation and has in regard to this, been shown to suppress tumor cell growth. During physical activity, which is associated with a reduced cancer risk, working muscles secrete myokines, known to activate AMPK. This could indicate a connection between AMPK activity, myokine release from the working muscle, and an anti-cancer response. We hypothesize that exercise-induced myokine secretion causes an anti-cancer response via AMPK activation. Methods: Exercise-induced AMPK activation was studied in two models, 1) A cell study using the two breast cancer cell lines, MDA-MB-231 and MCF-7, incubated with exercise-conditioned serum, representing a myokine pool. Serum was collected from 9 females during a 2 hours cycling bout, and during a subsequent 3 hours rest. Following incubation, cell viability and AMPK phosphorylation was determined in the cells. 2) An In Vivo model, where the two cell lines were injected into nude mice. When the tumors reached 6 mm in diameter, the mice were subjected to 1 hour forced swimming bout, after which the tumors were dissected and analyzed for pAMPK content. Results: 1) Cell study: Two hours of cycling induced a 6-fold increase in serum IL-6, as expected. Incubating cancer cells with this post-exercise serum resulted in a significant reduction in the viability of MCF-7 cells, while no effect on the viability of MDA-MB-231 cells were observed. Preliminary data show increased AMPK phosphorylation in both MDA-MB-231 and MCF-7 cells after incubation with 5% exercise-conditioned serum. 2) In vivo study: 1 hour of swimming resulted in significantly increased AMPK phosphorylation in the MCF-7 tumors. Conclusion: Our preliminary data indicate that exercise-induced factors can cause decreased viability and increased AMPK activity in MCF-7 cells, while MDA-MB-231 cells need further investigation. Acknowledgement: The Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National research Foundation (#02-512-55). This study was further supported by the Danish Medical Research Council and the Lundbeck Foundation. Citation Format: Grith W. Højfeldt, Christine Dethlefsen, Bente K. Pedersen, Pernille Hojman. Exercise activates AMP-activated protein kinase in breast cancer 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 5400. doi:10.1158/1538-7445.AM2013-5400
Ophthalmoscopic Signs of Death
Authors: B. Gluck
Journal: BMJ (1936)

Many spider venom-peptides are known to modulate the activity of the voltage-gated sodium channel NaV1.7, which has emerged as a promising analgesic target. A class of spider venom-peptides (NaSpTx1) in particular have been found to potently inhibit NaV1.7 (nanomolar IC50), and shown to produce analgesic effects in animals. However, one member of this family, μ TRTX Hhn2b (Hhn2b), does not inhibit mammalian NaV channels expressed in dorsal root ganglia at concentrations up to 100 μM. This peptide is classified as a NaSpTx1 member by virtue of its cysteine spacing and sequence conservation over functionally important residues. Here, we have performed detailed structural and functional analyses of Hhn2b leading us to identify two non-pharmacophore residues that contribute to hNaV1.7 inhibition by non-overlapping mechanisms. These findings allowed us to produce a double mutant of Hhn2b that shows nanomolar inhibition of hNaV1.7. Traditional structure/function analysis did not provide sufficient resolution to identify the mechanism underlying the observed gain of function. However, by solving the high-resolution structure of both the wild type and mutant peptides using advanced multidimensional NMR experiments, we were able to uncover a previously unknown network of interactions that stabilize the pharmacophore region of this class of venom-peptides. We further monitored the lipid binding properties of the peptides and identified that one of the key amino acid substitutions also selectively modulates the binding of the peptide to anionic lipids. These results will further aid the development of peptide-based analgesics for the treatment of chronic pain.
The art of representation: Support for an enactive approach
Authors: Natika Newton
Journal: Behavioral and Brain Sciences (2004)

Grush makes an important contribution to a promising way of viewing mental representation: as a component activity in sensorimotor processes. Grush shows that there need be no entities in our heads that would count as representations, but that, nevertheless, the process of representation can be defined so as to include both natural and artificial (e.g., linguistic or pictorial) representing.
Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury
Authors: Christian Woiciechowsky, Khusru Asadullah, Dirk Nestler, Beatrice Eberhardt, Cornelia Platzer, Britta Schöning, Frauke Glöckner, Wolfgang R. Lanksch, Hans-Dieter Volk, Wolf-Diatrich Döcke
Journal: Nature Medicine (1998)
Secondary Erythrocytosis Produced by the Tyrosine Kinase Inhibitors Sunitinib and Sorafenib
Authors: Doru T. Alexandrescu, Rebecca McClure, Haleh Farzanmehr, Constantin A. Dasanu
Journal: Journal of Clinical Oncology (2008)

myeloablative conditioning regimen and 80% of the patients in the RIC group.In the myeloablative group (n ϭ 79), 39 patients (49%) received the combination of cyclophosphamide plus TBI, 18 patients (23%) received busulfan plus cyclophosphamide, and 22 patients (28%) received other chemotherapy-containing protocols.In the RIC group (n ϭ 89), the vast majority of the patients received allograft with fludarabine-containing regimens: fludarabine plus melphalan, 30 patients (33%); fludarabine plus cyclophosphamide, 23 patients (26%); fludarabine plus busulfan, 12 patients (13%); and other combinations, nine patients (10%).Only seven patients (8%) received lowdose TBI in the conditioning regimen.Although the number of patients treated with low-dose TBI was low, all of them experienced relapse after transplantation and died as a result of disease progression.Intensity of conditioning regimen seems to be important, taking into account the heavily pretreated and sometimes refractory population of patients who are included in allogeneic protocols, as has been indicated by others. 5
The burden of chronic kidney disease
Authors: Rizwan A Hamer, A Meguid El Nahas
Journal: BMJ (2006)

Is rising rapidly worldwide 

T he number of patients with chronic kidney disease worldwide is rising markedly.1 In the United Kingdom, the annual incidence of end stage renal disease is around 100 per 1 000 000 population.2 This incidence has doubled over the past decade and is expected to continue to rise by 5-8% annually, but it remains well below the European average (around 135/1 000 000) and that of the United States (336/1 000 000).3

Disparities in the incidence of end stage renal disease within and between developed countries reflect racial and ethnic diversity. In the US, the annual incidence is 256/1 000 000 in white people compared with 982/1 000 000 in African-Americans.3 In Australia, the incidence in white people is comparable to that in the UK (94/1 000 000), but the incidence in aboriginals is 420/1 000 000.

The rise in end stage renal disease worldwide most probably reflects the global epidemic of type 2 diabetes and the ageing of the populations in developed countries, with a higher incidence in elderly people (the annual incidence in people over 65 in the …
New era of public access to federally funded trials begins
Authors: Jeanne Lenzer
Journal: BMJ (2005)

A new era in public access to the results of medical research starts next week, as the policy of the US National Institutes of Health (NIH) to ask all investigators who receive federal funds to make their results freely available comes into effect.

Dr Robert Steinbrook, a national correspondent for the New England Journal of Medicine , predicts in the journal this week that some journal editors and publishers will be “riled” by the recommendations initiated by Dr Elias Zerhouni, director of the NIH (2005;352:1739).

Dr Zerhouni has asked researchers whose work was supported by public funding to voluntarily submit an electronic …
2007 4 WEEK THERAPY WITH THE NON-NUCLEOSIDIC POLYMERASE INHIBITOR BI207127 IN COMBINATION WITH PEGINTERFERON-ALFA2A AND RIBAVIRIN IN TREATMENT NAIVE AND TREATMENT EXPERIENCED CHRONIC HCV GT1 PATIENTS
Authors: D. Larrey, A. Lohse, V. de Ledinghen, C. Trepo, T. Gerlach, J.-P. Zarski, A. Tran, P. Mathurin, R. Thimme, K. Arastéh, C. Trautwein, A. Cerny, N. Dikopoulos, M. Schuchmann, M.H. Heim, G. Gerken, J. Stern, K. Wu, N. Abdallah, B. Girlich, S. Josepf, B. Wulf, F. Berger, J. Steffgen
Journal: Journal of Hepatology (2010)
How much are doctors worth: is doctors' self interest undermining the NHS?
Authors: Ian Quigley
Journal: BMJ (2007)

Until 2004, general practitioners were responsible for the care of their registered patients 24 hours a day and seven days a week.They did not have to provide that care themselves but remained responsible for arranging and coordinating it.As a result of the new GP contract, most general practitioners have now opted out of this responsibility and are contracted to work for the NHS from 8 am to 6 30 pm and for only five days a week.
Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s
Authors: N Goodson
Journal: Annals of the Rheumatic Diseases (2005)

There is increased cardiovascular disease mortality in rheumatoid arthritis. This may reflect an increased prevalence of cardiovascular disease or an increased case fatality in patients with rheumatoid arthritis.To examine whether rheumatoid patients with disease onset in the 1980s-1990s have increased mortality, and to compare cardiovascular admission rates in rheumatoid patients with those of the general population.An inception cohort of 1010 rheumatoid patients attending Stockport rheumatology clinics between 1981 and 1996 was followed up to December 2002 through the Office for National Statistics. Standardised mortality ratios (SMR) were calculated for all-cause and cause specific mortality, using the population of Stockport as reference. Cardiovascular disease admission rates were ascertained for a subgroup of patients using national hospital episode statistics; standardised cardiovascular disease admission rates (SAR) and SMRs were calculated for this subgroup.470 patients (48%) died during a median follow up of 11.4 years. All-cause mortality was increased in men (SMR = 1.45 (95% confidence interval, 1.22 to 1.71)) and women (SMR = 1.84 (1.64 to 2.05)), as was cardiovascular disease mortality in men (SMR = 1.36 (1.04 to 1.75) and women (SMR = 1.93 (1.65 to 2.26)). No difference in cardiovascular disease admission rates was observed in men (SAR 1.20 (0.89 to 1.58) or women (SAR = 1.10 (0.88 to 1.36)), despite excess cardiovascular disease mortality in this subgroup.Patients with rheumatoid arthritis have reduced life expectancy and excess cardiovascular disease mortality. Nevertheless, standardised admission rates for cardiovascular disease were not raised. This suggests either that cardiovascular disease in rheumatoid arthritis has a higher case fatality than in the general population or that it often goes unrecognised before the fatal event.
PTU-199 Proinflammatory Cytokine (Il-8) in Microscopic Enteritis
Authors: K Rostami, M Rostami Nejad, H Asadzadeh, M R Zali
Journal: Gut (2013)

<h3>Introduction</h3> Celiac disease (CD) is an autoimmune disorder that is triggered by an immune response to gluten in genetically predisposed individuals. Interleukin-8 (IL-8) is produced by macrophages, epithelial cells and endothelial cells. Therefore, IL8 has an important role in the innate immune response and associated with inflammation. The aim of this study is to evaluate the elevation of IL8 level in patients with celiac diseasecompare with control group. <h3>Methods</h3> Fifty three confirmed treated or untreated celiac disease patients referred to Taleghani hospital, Iran as cases were matched according to age and gender with 300 healthy controls, screened with ELISA to determine the level of IL8. <h3>Results</h3> Serum IL8 levels were evaluated in all patients with positive CD compare to healthy control. The minimum level of IL8 in cases was 16.3 and maximum level was 397.7. On the other side the minimum and maximum level of IL8 in controls was 10.3 and 397.7 respectively. The mean level of IL8 in celiac disease patients was 116.8 compare with 84.8 in healthy control. This differences was statistically significant between 2 groups (p = 0.0001). <h3>Conclusion</h3> Increased serum levels of pro-inflammatory cytokines such as IL8 seem to be increased in patients with celiac disease. It is the inflammation inherent in gluten sensitivity rather than mucosal atrophy that results in malabsorption and nutrient deficiency. Our findings suggest that higher level of IL8 in patients with celiac disease characterise the higher inflammatory response of this disease in the active phase. The inflammatory response including increasing the level of IL-8 may cause or not damage to the intestinal mucosa but in both cases lead to increased permeability of the intestinal epithelium. <h3>Disclosure of Interest</h3> None Declared
Late onset membranous nephropathy complicating donor lymphocyte infusion for Leukaemia relapse after allogeneic stem cell transplantation
Authors: M.F. Lam, W.Y. Au, K.C. Tse, T.M. Chan, G.S.W. Chan, K.W. Chan, K.N. Lai
Journal: American Journal of Hematology (2006)

To the Editor: Renal damage after stem cell transplantation (SCT) may manifest as acute renal failure, renal tubular acidosis, and proteinuria [1].Post-SCT nephrotic syndrome (NS) has histological association with membranous nephropathy.It usually accompanies acute/chronic graft versus host disease (aGVHD/cGVHD) [2], and represents kidney damage mediated by donor lymphocytes.By natural history, GVHD severity usually decreases with time.However, therapeutic induction of GVHD by donor lymphocyte infusion (DLI) may be needed to enhance the graft versus leukemia (GVL) effect.The clinical spectrum of DLI-related GVHD is often different from that after initial SCT [3].Very little is known about the manifestation, histology, and optimal treatment for DLI related glomerulonephritis [4].A 27-year-old man with chronic myeloid leukemia (CML) received SCT from an unrelated donor.He was engrafted with grade I aGVHD with no cGVHD.Cyclosporine (CsA) was tailed-off at 1 year.However, molecular and cytogenetic relapse of CML occurred at 36 months.Two doses of DLI (3.5 Â 10 5 lymphocytes/kg) produced complete molecular remission, accompanied Fig. 1.Electron microscopy shows discrete electron-dense deposits in the subepithelial region (original magnification 33,900).
Myocardial Perfusion Scans
Authors: Amy Berrington de Gonzalez, Kwang-Pyo Kim, Rebecca Smith-Bindman, Dorothea McAreavey
Journal: Circulation (2010)

Background— Myocardial perfusion scans contribute up to 20% of the estimated annual collective radiation dose to the US population. We estimated potential future cancer risk from these scans by age at exposure and current frequency of use in the United States. Methods and Results— Usage patterns were determined from national survey data, and radionuclide dosage was based on current guidelines. Cancer risk projection models were generated on the basis of the National Research Council Biological Effects of Ionizing Radiation VII report, under the assumption that risk has a linear relationship with radiation exposure even at low doses. The mean projected number of radiation-related incident cancers and 95% uncertainty intervals were estimated with the use of Monte Carlo simulations. Estimated risks for a scan performed at age 50 years ranged from 2 cancers per 10 000 scans (95% uncertainty interval, 1 to 5) for a positron emission tomography ammonia-13 test to 25 cancers per 10 000 scans (95% uncertainty interval, 9 to 58) for a dual-isotope (thallium-201 plus technetium-99m) scan. Risks were 50% lower at age 70 years but were similar for men and women. The combination of cancer risk estimates and data on frequency of use suggests that the 9.1 million myocardial perfusion scans performed annually in the United States could result in 7400 (95% uncertainty interval, 3300 to 13 700) additional future cancers. Conclusions— The lifetime cancer risk from a single myocardial perfusion scan is small and should be balanced against likely benefit and appropriateness of the test. The estimates depend on a number of assumptions, including life expectancy. They apply directly to asymptomatic individuals with life expectancies similar to those of the general population. For individuals with a symptomatic clinical profile, on whom such scans are typically performed, the risks will be lower because of shorter life expectancy.
STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES
Authors: Victor V. Bergs, Gertrude Henle, Friedrich Deinhardt, Werner Henle
Journal: The Journal of Experimental Medicine (1958)

Efforts were made to elucidate the nature of the resistance to vesicular stomatitis virus (VSV) observed in MCN cultures persistently infected with Newcastle disease, mumps, or 6-6 viruses (MCN(NDV), MCN(Mps) and MCN(6-6), respectively). Cells derived from persistently infected cultures adsorbed VSV to the same extent as their uninfected counterparts. Only a fraction of the adsorbed virus could be recovered from the cells indicating that it enters into an eclipse in all of the cell types. While propagation of VSV in MCN cells is largely inhibited at low pH levels, the resistance of persistently infected cultures could not be ascribed to their increased lactic acid formation. Resistance was not absolute in that a few cells in persistently infected cultures apparently supported VSV reproduction. Furthermore resistance of the cultures was found to be transitory in that the VSV infection gradually gained the upper hand after 2 to 4 weeks of incubation. Addition of ultraviolet-inactivated NDV to MCN cultures induced resistance to VSV as long as the equivalent of at least one ID(50) (for chick embryos) of inactivated virus was provided per cell. Establishment of resistance required some time and its duration depended upon whether or not the free inactivated NDV was removed or neutralized after given adsorption periods. The transitory nature of resistance in persistently infected cultures, or in MCN cells following adsorption of inactivated NDV, is most likely explained by the fact that the cells continue to divide and that the daughter cells are, at least in part, susceptible to VSV. The results are compatible with the conclusion that the resistance observed represents another example of interference between 2 viruses.
Impact of the Medicare Fee Schedule on Payments to Physicians
Authors: Jesse M. Levy, Michael J. Borowitz, Stephen F. Jencks, Terrence L. Kay, Deborah K. Williams
Journal: JAMA (1990)

Beginning in 1992, the Medicare program will pay physicians by the Medicare Fee Schedule, a system of geographically adjusted standardized payment rates based in part on the Resource-Based Relative Value Scale developed by Hsaio et al and in part on current Medicare payments. In our simulations of the Medicare Fee Schedule, we find that (1) redistributions of Medicare-allowed charges across specialities will be substantial but approximately only half the size projected by Hsaio, (2) there will be large redistributions among geographic areas that tend to compound the specialty redistributions, and (3) there will be wide variation within specialties as to how individual providers are affected. The majority of the redistributive impact of the Medicare Fee Schedule is attributable to implementation of a geographically adjusted system of standardized payments rather than to the particular work values developed by Hsiao et al in the Resource-Based Relative Value Scale.
Monoclonal antibodies against complement 3 neoantigens for detection of immune complexes and complement activation. Relationship between immune complex levels, state of C3, and numbers of receptors for C3b.
Authors: M T Aguado, J D Lambris, G C Tsokos, R Burger, D Bitter-Suermann, J D Tamerius, F J Dixon, A N Theofilopoulos
Journal: Journal of Clinical Investigation (1985)

C3-bearing immune complexes and C3 activation products were detected by using two monoclonal antibodies, one specific for a neoantigenic determinant on C3c and the other for C3d. To quantitate immune complexes, the anti-C3c or anti-C3d antibodies were fixed to microtiter plates and reacted with test plasma. The binding of C3-bearing immune complexes in this plasma was then measured with radioisotope- or enzyme-labeled anti-human IgG. To test for C3 breakdown products, solid-phase monoclonal antibody to the C3d neoantigen was reacted with EDTA-plasma samples, and fixed iC3b or C3d was measured with a polyclonal anti-C3 antibody. Patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome, and paracoccidioidomycosis were found to contain immune complexes bearing C3b/iC3b or C3d. In most conditions, there were more C3d-containing immune complexes than C3b/iC3b. Although CR1 (C3b receptors) rapidly converted immune complex-bound iC3b to C3dg/C3d and lupus patients had reduced CR1, no correlation between the state of C3 on circulating immune complexes or levels of immune complexes and CR1 numbers was seen. However, levels of C3-fixing ICs correlated with levels of C3 activation products. This assay system with monoclonal antibodies to neoantigens expressed on activated, but not native, C3 provides sensitive and specific means for detecting and classifying C3-fixing immune complexes and for assessing C3 activation.
Generation of T Follicular Helper Cells Is Mediated by Interleukin-21 but Independent of T Helper 1, 2, or 17 Cell Lineages
Authors: Roza I. Nurieva, Yeonseok Chung, Daehee Hwang, Xuexian O. Yang, Hong Soon Kang, Li Ma, Yi-hong Wang, Stephanie S. Watowich, Anton M. Jetten, Qiang Tian, Chen Dong
Journal: Immunity (2008)
Graves’ Disease after the Onset of Panic Disorder
Authors: Sunao Matsubayashi, Hajime Tamai, Yoshiaki Matsumoto, Kei-ichi Tamagawa, Toshio Mukuta, Tetsuya Morita, Chiharu Kubo
Journal: Psychotherapy and Psychosomatics (1996)

It is still unknown whether anxiety disorders observed in Graves' disease are a consequence of increased thyroid hormone levels or precede the onset of Graves' disease.Two case reports are described.In 2 patients Graves' disease occurred in the setting of previously established euthyroid panic disorder. The interval between the onset of panic disorder and that of hyperthyroidism was 4 and 5 years, respectively. Antithyroid drug treatment reduced psychiatric symptoms, but only to a partial degree.The findings indicate that panic disorder may not only be a consequence of Graves' disease but may precede its onset and potentially predispose to its development.