tbuckley/cabot-search huggingface dataset:
New Editorial Team for Neuro-Oncology
Authors: P. Y. Wen
Journal: Neuro-Oncology (2013)

It is a great privilege and honor for me to assume the role of Editor-In-Chief of Neuro-Oncology. It is particularly humbling to follow in the footsteps of Dr. Darrell Bigner, who founded the journal in 1999, and Dr. W. K. Alfred Yung, who has been Editor-In-Chief since 2007. Dr. Yung, Chairman of the Department of Neuro-Oncology at M.D. Anderson Cancer Center, has done a remarkable job during his tenure over the past 7 years. He oversaw the transition of the journal from Duke University Press to Oxford University Press and the very successful growth from 4 issues a year to the current 12 issues annually with up to 5 supplements. During his tenure the number of articles submitted each year increased from approximately 270 in 2007 to over 800 in 2013, and the number of published articles increased from 52 to over 170. Most importantly, he has increased the quality and importance of the publications, raising its impact factor in 2012 to 6.18, making it the highest-ranking journal in the field of neuro-oncology, 10th of 192 clinical neurology journals, and 24th of 196 oncology journals. We are very grateful for his tireless efforts, leadership, and vision that have made Neuro-Oncology so successful.
Intrathyroidal persistence of human parvovirus B19 DNA in a patient with Hashimoto's thyroiditis
Authors: Kouki Mori, Yasuhiko Munakata, Takako Saito, Jun-ichi Tani, Yoshinori Nakagawa, Saeko Hoshikawa, Hiroshi Ozaki, Sadayoshi Ito, Katsumi Yoshida
Journal: Journal of Infection (2007)
Genetic analysis of de novo CD5+ diffuse large B-cell lymphomas suggests an origin from a somatically mutated CD5+ progenitor B cell
Authors: Tiemo Katzenberger, Andreas Lohr, Stephan Schwarz, Martin Dreyling, Julia Schoof, Christina Nickenig, Stephan Stilgenbauer, Jörg Kalla, M. Michaela Ott, Hans Konrad Müller-Hermelink, German Ott
Journal: Blood (2002)
Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial
Authors: Wolfgang Wick, Michael Platten, Christoph Meisner, Jörg Felsberg, Ghazaleh Tabatabai, Matthias Simon, Guido Nikkhah, Kirsten Papsdorf, Joachim P Steinbach, Michael Sabel, Stephanie E Combs, Jan Vesper, Christian Braun, Jürgen Meixensberger, Ralf Ketter, Regine Mayer-Steinacker, Guido Reifenberger, Michael Weller
Journal: The Lancet Oncology (2012)
The effect of the orally active platelet-activating factor antagonist WEB 2086 in the treatment of asthma.
Authors: D P Spence, S L Johnston, P M Calverley, P Dhillon, C Higgins, E Ramhamadany, S Turner, A Winning, J Winter, S T Holgate
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Platelet-activating factor (PAF) may be a major mediator of asthma and bronchial hyperreactivity through its many proinflammatory actions. Specific antagonism of PAF might offer an alternative anti-inflammatory treatment to inhaled corticosteroids. To test this, we have studied the effect of an orally active PAF antagonist, WEB 2086, on the inhaled steroid requirements of symptomatic atopic asthmatics in a double-blind randomized placebo-controlled parallel group study. The inhaled corticosteroid dose required for symptomatic control of asthma was established and further steroid reduction was attempted after treatment with WEB 2086 40 mg three times daily for 12 wk. Of 106 patients recruited, 68 entered the treatment phase and 65 completed 6 wk of treatment. The mean daily corticosteroid dose (SE) at study entry was 1,257 (75) micrograms which was reduced by 323 (66) micrograms during the run-in period without loss of symptomatic control. A further 416 (57) micrograms reduction in inhaled corticosteroid dosage was possible during the treatment phase but this was almost identical in the WEB 2086 and placebo-treated groups, amounting to 353 (92) and 481 (65) micrograms/day respectively (not significant [NS]). Rate of relapse following corticosteroid reduction was a continuous variable and relapse occurred at different times depending on the variable used to define it. Time to relapse measured by an increase in symptoms correlated with disease duration (r = 0.41, p < 0.01) and with the dose of inhaled corticosteroid at study entry (r = 0.36, p < 0.01) but no other measured variable predicted the time to relapse.(ABSTRACT TRUNCATED AT 250 WORDS)
Functional modulation of the transient outward current Ito by KCNE β-subunits and regional distribution in human non-failing and failing hearts
Authors: S RADICKE, D COTELLA, E GRAF, U BANSE, N JOST, A VARRO, G TSENG, U RAVENS, E WETTWER
Journal: Cardiovascular Research (2006)

The function of Kv4.3 (KCND3) channels, which underlie the transient outward current I(to) in human heart, can be modulated by several accessory subunits such as KChIP2 and KCNE1-KCNE5. Here we aimed to determine the regional expression of Kv4.3, KChIP2, and KCNE mRNAs in non-failing and failing human hearts and to investigate the functional consequences of subunit coexpression in heterologous expression systems.We quantified mRNA levels for two Kv4.3 isoforms, Kv4.3-S and Kv4.3-L, and for KChIP2 as well as KCNE1-KCNE5 with real-time RT-PCR. We also studied the effects of KCNEs on Kv4.3+KChIP2 current characteristics in CHO cells with the whole-cell voltage-clamp method.In non-failing hearts, low expression was found for KCNE1, KCNE3, and KCNE5, three times higher expression for KCNE2, and 60 times higher for KCNE4. Transmural gradients were detected only for KChIP2 in left and right ventricles. Compared to non-failing tissue, failing hearts showed higher expression of Kv4.3-L and KCNE1 and lower of Kv4.3-S, KChIP2, KCNE4, and KCNE5. In CHO cells, Kv4.3+KChIP2 currents were differentially modified by co-expressed KCNEs: time constants of inactivation were shorter with KCNE1 and KCNE3-5 while time-to-peak was decreased, and V(0.5) of steady-state inactivation was shifted to more negative potentials by all KCNE subunits. Importantly, KCNE2 induced a unique and prominent 'overshoot' of peak current during recovery from inactivation similar to that described for human I(to) while other KCNE subunits induced little (KCNE4,5) or no overshoot.All KCNEs are expressed in the human heart at the transcript level. Compared to I(to) in native human myocytes, none of the combination of KChIP2 and KCNE produced an ideal congruency in current characteristics, suggesting that additional factors contribute to the regulation of the native I(to) channel.
The Role of Voltage-Gated Calcium Channels in Pancreatic β-Cell Physiology and Pathophysiology
Authors: Shao-Nian Yang, Per-Olof Berggren
Journal: Endocrine Reviews (2006)

Voltage-gated calcium (CaV) channels are ubiquitously expressed in various cell types throughout the body. In principle, the molecular identity, biophysical profile, and pharmacological property of CaV channels are independent of the cell type where they reside, whereas these channels execute unique functions in different cell types, such as muscle contraction, neurotransmitter release, and hormone secretion. At least six CaValpha1 subunits, including CaV1.2, CaV1.3, CaV2.1, CaV2.2, CaV2.3, and CaV3.1, have been identified in pancreatic beta-cells. These pore-forming subunits complex with certain auxiliary subunits to conduct L-, P/Q-, N-, R-, and T-type CaV currents, respectively. beta-Cell CaV channels take center stage in insulin secretion and play an important role in beta-cell physiology and pathophysiology. CaV3 channels become expressed in diabetes-prone mouse beta-cells. Point mutation in the human CaV1.2 gene results in excessive insulin secretion. Trinucleotide expansion in the human CaV1.3 and CaV2.1 gene is revealed in a subgroup of patients with type 2 diabetes. beta-Cell CaV channels are regulated by a wide range of mechanisms, either shared by other cell types or specific to beta-cells, to always guarantee a satisfactory concentration of Ca2+. Inappropriate regulation of beta-cell CaV channels causes beta-cell dysfunction and even death manifested in both type 1 and type 2 diabetes. This review summarizes current knowledge of CaV channels in beta-cell physiology and pathophysiology.
Ethics and conflicts of interest in the BJD
Authors: D.J. Eedy, R.A.C. Graham-Brown
Journal: British Journal of Dermatology (2004)

The British Journal of Dermatology aims to publish high quality clinical and scientific papers that have undergone rigorous statistical and peer review.However, even the very best reviewers may not be able to detect subtle influences asserted by the pharmaceutical industry when a company has sponsored a drug trial, partially or completely written the manuscript or had a medical writer do so on behalf of the authors.Drug companies often prefer to purchase and distribute reprints of a favourable editorial mention of their products, especially when they are perceived as independent and authoritative, over an advertisement, as they see the former as more powerful.Conflicts of interest have been defined as Ôthose of a financial nature that, through their potential influence on behaviour or content or from perception of such potential influences, could undermine the objectivity, integrity or perceived value of a publicationÕ. 1Having a conflict of interest and publishing the results of sponsored drug trials is not, in itself, wrong.Some of the best clinical trials have been designed, constructed and sponsored by pharmaceutical companies.The problem arises when authors do not adequately inform the editors and the readers of potential conflicts of interest.To be informed decision-makers, readers need to be aware of the potential conflicts of interest and take this into account when critically interpreting the results of such articles.Conflicts of interest with the pharmaceutical companies may arise at any stage of the process.These include the original design of the study, funding, interpretation of the data or the writing of the manuscript submitted for publication. 2,3Hence, the interaction between the authors and investigators in a trial and the sponsoring pharmaceutical company can be highly complex and may be open to manipulation.Because of this it can be difficult to distinguish between dishonesty, honest bias and the use of ÔspinÕ by pharmaceutical companies for extravagant claims.It can result in omission or camouflage of unfavourable data; evidence exists that a large number of
Blood pressure variability increases connexin expression in the vascular smooth muscle of rats
Authors: M. L. Rocha, A. H. Kihara, A. P. Davel, L. R.G. Britto, L. V. Rossoni, L. M. Bendhack
Journal: Cardiovascular Research (2008)

Following sinoaortic denervation (SAD), isolated rat aortas present oscillatory contractions and demonstrate a heightened contraction for alpha-adrenergic agonists. Our aim was to verify the effects of SAD on connexin43 (Cx43) expression and phenylephrine-induced contraction in isolated aortas.Three days after surgery (SAD or sham operation), isolated aortic rings were exposed to phenylephrine and acetylcholine (0.1-10 microM) in the presence or absence of the gap junction blocker 18beta-glycyrrhetinic acid (18beta-GA, 100 microM). Vascular reactivity to potassium chloride (KCl, 4.7-120 mM) was also examined. The incidence of rats presenting oscillatory contractions was measured. Effects of SAD on the vascular smooth muscle expression of the Cx43 mRNA by RT-PCR and western blotting for Cx43 protein were examined. Phenylephrine-induced contraction was higher in SAD rat aortas compared with the control. In the presence of 18beta-GA, the response to phenylephrine was similar in both groups. Oscillatory contractions were observed in 10/10 SAD rat aortas vs. 2/10 controls. Relaxing response to acetylcholine was similar in both groups, but in the presence of 18beta-GA, the response to acetylcholine decreased significantly in the sham-operated group (82.7 +/- 7.6% reduction of relaxation), whereas a half-maximal relaxation (reduction of 46.2 +/- 5.3%) took place in SAD rat aortas. KCl-induced contraction was similar in both groups. Following SAD, RT-PCR revealed significantly increased levels of Cx43 mRNA (9.85 fold, P < 0.01). Western blot analysis revealed greater levels of Cx43 protein (P < 0.05).Blood pressure variability evoked by SAD leads to increased expression of Cx43, which could contribute to enhanced phenylephrine-induced contraction and oscillatory activity in isolated aortas.
Ca <sup>2+</sup> Waves in Lung Capillary Endothelium
Authors: Xiaoyou Ying, Yoshihiro Minamiya, Chenzhong Fu, Jahar Bhattacharya
Journal: Circulation Research (1996)

Although cytosolic Ca 2+ importantly regulates organ function, lung microvascular [Ca 2+ ] i regulation remains poorly understood because of the lack of direct in situ quantification. In the present study, we report the first endothelial [Ca 2+ ] i quantification by the fura 2 method in microscopically imaged venular capillaries of the isolated blood-perfused rat lung. Sequential images indicated the presence of intercellular Ca 2+ waves that spontaneously originated from pacemaker endothelial cells and then spread for short distances along the capillary wall, inducing synchronous endothelial [Ca 2+ ] i oscillations. Fast Fourier analyses of the oscillations revealed a dominant wave component with an amplitude of 37 nmol/L, frequency of 0.4 min −1 , and velocity of 5 μm/s. The intracellular Ca 2+ wave was unaffected by blood flow stoppage or by infusions of Ca 2+ -containing or Ca 2+ -free dextran. Inhibition of the wave by thapsigargin in Ca 2+ -free dextran and by the gap junction uncoupler, heptanol, indicated that it was generated by endosomal Ca 2+ release in the pacemaker cell and was propagated by gap junctional communication. In the presence of histamine, enhancement of the wave accounted for a significant component of the coordinated [Ca 2+ ] i increase in the capillary segment. No intercellular Ca 2+ waves were evident in adjoining alveolar epithelial cells. Our findings indicate a novel mechanism of [Ca 2+ ] i regulation in the lung capillary under both resting and stimulated conditions. Pacemaker-induced Ca 2+ waves, generated intracellularly by unknown initiating mechanisms, communicated to adjoining cells to determine [Ca 2+ ] i profiles in short interbranch segments of capillary walls.
The Hippo pathway effector YAP controls mouse hepatic stellate cell activation
Authors: Inge Mannaerts, Sofia Batista Leite, Stefaan Verhulst, Sofie Claerhout, Nathalie Eysackers, Lien F.R. Thoen, Anne Hoorens, Hendrik Reynaert, Georg Halder, Leo A. van Grunsven
Journal: Journal of Hepatology (2015)
Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP)
Authors: Eva H. N. Olsen, Arlene S. McCain, Elizabeth P. Merricks, Thomas H. Fischer, Ivy M. Dillon, Robin A. Raymer, Dwight A. Bellinger, Scot A. Fahs, Robert R. Montgomery, James C. Keith, Robert G. Schaub, Timothy C. Nichols
Journal: Blood (2003)
The International Monetary Fund and the Ebola outbreak
Authors: Alexander Kentikelenis, Lawrence King, Martin McKee, David Stuckler
Journal: The Lancet Global Health (2014)

In recent months, the International Monetary Fund (IMF) has announced US$430 million of funding to fight Ebola in Sierra Leone, Guinea, and Liberia.1 By making these funds available, the IMF aims to become part of the solution to the crisis, even if this involves a departure from its usual approach. As IMF Director Christine Lagarde said at a meeting on the outbreak, “It is good to increase the fiscal deficit when it's a matter of curing the people, of taking the precautions to actually try to contain the disease.
ICF based comparison of disease specific instruments measuring physical functional ability in ankylosing spondylitis
Authors: T Sigl
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To link validated and widely used instruments measuring physical functional ability in ankylosing spondylitis to the International Classification of Functioning, Disability, and Health (ICF) and to compare their contents, based on the results of the linking process. <b>Methods:</b> The Bath Ankylosing Spondylitis Functional Index (BASFI), the Dougados Functional Index (DFI), the Health Assessment Questionnaire modified for the spondylarthropathies (HAQ-S), and the Revised Leeds Disability Questionnaire (RLDQ) were linked to the ICF separately by two trained health professionals according to 10 linkage rules. <b>Results:</b> All concepts contained in the items of the selected instruments could be successfully linked to the ICF except for “illness” included in the HAQ-S. Altogether 55 different ICF categories were linked. Seven belonged to “body functions”, 43 to “activities and participation”, and five to “environmental factors”. The component “body structure” was not contained in any of the four instruments. Only two ICF categories were common to all selected questionnaires, but there was a high level of concordance on the concepts represented in them. However, especially in terms of “activities and participation”, the emphasised aspects differed. <b>Conclusions:</b> The ICF provides an excellent common framework for the comparison of disease specific instruments for ankylosing spondylitis. For a future revision of the ICF, a specification of major limitations in patients with ankylosing spondylitis is suggested.
Biliary lipid secretion in chronic cholestatic liver disease.
Authors: Y A Kesaniemi, M P Salaspuro, M Vuoristo, T A Miettinen
Journal: Gut (1982)

Biliary lipid secretion rates, faecal steroids, and serum lipids were studied in patients with chronic cholestatic liver disease mainly primary biliary cirrhosis. The biliary secretion of cholesterol, bile acids, and phospholipids was markedly decreased as compared with those in the control group and in general correlated negatively with the serum cholesterol and triglyceride values. The molar percentage of cholesterol was increased in the hepatic bile. This suggests that, in cholestatic liver disease, in contrast with the normal state, the hapatic bile may be supersaturated postprandially. Faecal bile acids and neutral sterols of cholesterol origin were decreased proportionately to the corresponding biliary lipid secretion rates. In fact, both biliary and faecal steroid outputs were only about a half or less than those in the controls, indicating that the fractional absorption was not changed but absolute absorption and faecal steroid excretion were low in patients with chronic cholestatic liver disease. Thus, despite low cholesterol and bile acid absorption, cholesterol and bile acid synthesis is low. A negative correlation between faecal steroids and serum cholesterol suggests that the high serum cholesterol level contributed to regulation of cholesterol synthesis.
Butyrate-induced colonic hypersensitivity is mediated by mitogen-activated protein kinase activation in rat dorsal root ganglia
Authors: Dabo Xu, Xiaoyin Wu, Gintautas Grabauskas, Chung Owyang
Journal: Gut (2012)

<h3>Objective</h3> Increased faecal butyrate levels have been reported in irritable bowel syndrome. Rectal instillation of sodium butyrate (NaB) increases visceral sensitivity in rats by an unknown mechanism. We seek to examine the signal transduction pathways responsible for the enhanced neuronal excitability in the dorsal root ganglion (DRG) following NaB enemas and demonstrate that this is responsible for the colonic hypersensitivity reported in this animal model. <h3>Design</h3> Colorectal distention (CRD) studies were performed in rats treated with NaB rectal instillation with/without intrathecal or intravenous administration of mitogen-activated protein (MAP) kinase kinase inhibitor U0126. Western blot analysis and immunocytochemistry studies elucidated intracellular signalling pathways that modulate <i>I</i><sub>A</sub>. Patch-clamp recordings were performed on isolated DRG neurons treated with NaB, with/without U0126. <h3>Results</h3> Visceromotor responses (VMR) were markedly enhanced in NaB-treated rats. Western blot analysis of DRG neurons from NaB-treated rats showed a 2.2-fold increase in phosphorylated ERK1/2 (pEKR1/2) and 1.9-fold increase in phosphorylated voltage-gated potassium channel subunit 4.2 (pKv4.2). Intrathecal or intravenous administration of U0126 reduced VMR to CRD in NaB-treated rats and prevented increases in pERK1/2 and pKv4.2. Patch-clamp recordings of isolated DRG neurons showed that NaB caused a reduction in <i>I</i><sub>A</sub> to 48.9%±1.4% of control and an increase in neuronal excitability, accompanied by a twofold increase in pERK1/2 and pKv4.2. Concurrent U0126 administration prevented these changes. <h3>Conclusions</h3> Visceral hypersensitivity induced by colonic NaB treatment is mediated by activation of the MAP kinase–ERK1/2 pathway, which phosphorylates Kv4.2. This results in a reduction in <i>I</i><sub>A</sub> and an enhancement of DRG neuronal excitability.
Increased CD36 protein as a response to defective insulin signaling in macrophages
Authors: Chien-Ping Liang, Seongah Han, Haruka Okamoto, Ronald Carnemolla, Ira Tabas, Domenico Accili, Alan R. Tall
Journal: Journal of Clinical Investigation (2004)

Accelerated atherosclerosis is a major cause of morbidity and death in insulin-resistant states such as obesity and the metabolic syndrome, but the underlying mechanisms are poorly understood. We show that macrophages from obese (ob/ob) mice have increased binding and uptake of oxidized LDL, in part due to a post-transcriptional increase in CD36 protein. Macrophages from ob/ob mice are also insulin resistant, as shown by reduced expression and signaling of insulin receptors. Three lines of evidence indicate that the increase in CD36 is caused by defective insulin signaling: (a) Treatment of wild-type macrophages with LY294002, an inhibitor of insulin signaling via PI3K, results in an increase in CD36; (b) insulin receptor knockout macrophages show a post-transcriptional increase in CD36 protein; and (c) administration of thiazolidinediones to intact ob/ob mice and ob/ob, LDL receptor-deficient mice results in a reversal of macrophage insulin receptor defects and decreases CD36 protein. The last finding contrasts with the increase in CD36 that results from treatment of macrophages with these drugs ex vivo. The results suggest that defective macrophage insulin signaling predisposes to foam cell formation and atherosclerosis in insulin-resistant states and that this is reversed in vivo by treatment with PPAR-gamma activators.