tbuckley/cabot-search huggingface dataset:
Extracellular Signal-Regulated Kinase Is a Target of Cyclooxygenase-1-Peroxisome Proliferator-Activated Receptor-δ Signaling in Epithelial Ovarian Cancer
Authors: Takiko Daikoku, Susanne Tranguch, Anindita Chakrabarty, Dingzhi Wang, Dineo Khabele, Sandra Orsulic, Jason D. Morrow, Raymond N. DuBois, Sudhansu K. Dey
Journal: Cancer Research (2007)

Abstract The underlying causes of epithelial ovarian cancer (EOC) are unclear, and treatment options for patients with advanced disease are limited. There is evidence that the use of nonsteroidal anti-inflammatory drugs is associated with decreased risk of developing EOC. Nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX)-1 and COX-2, which catalyze prostaglandin biosynthesis. We previously showed that mouse and human EOCs have increased levels of COX-1, but not COX-2, and a COX-1–selective inhibitor, SC-560, attenuates prostaglandin production and tumor growth. However, the downstream targets of COX-1 signaling in EOC are not yet known. To address this question, we evaluated peroxisome proliferator-activated receptor δ (PPARδ) expression and function in EOC. We found that EOC cells express high levels of PPARδ, and neutralizing PPARδ function reduces tumor growth in vivo. More interestingly, aspirin, a nonsteroidal anti-inflammatory drug that preferentially inhibits COX-1, compromises PPARδ function and cell growth by inhibiting extracellular signal-regulated kinases 1/2, members of the mitogen-activated protein kinase family. Our study, for the first time, shows that whereas PPARδ can be a target of COX-1, extracellular signal-regulated kinase is a potential target of PPARδ. The ability of aspirin to inhibit EOC growth in vivo is an exciting finding because of its low cost, lack of cardiovascular side effects, and availability. [Cancer Res 2007;67(11):5285–92]
Hepatobiliary transport of hepatic 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors conjugated with bile acids
Authors: Ernst Petzinger, Lutz Nickau, Jurgen A. Horz, Siegfried Schulz, Gunther Wess, Alfons Enhsen, Eugen Falk, Karl-Heinz Baringhaus, Heiner Glombik, Axel Hoffmann, Stefan Müllner, Georg Neckermann, Werner Kramer
Journal: Hepatology (1995)

To obtain prodrugs with affinity to liver parenchymal cells, the hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors HR 780 and lovastatin (syn. mevinolin) were conjugated with the bile acids cholic acid, taurocholic acid, and glycocholic acid. Hepatic uptake and biliary excretion of the coupled drugs were investigated and compared with the noncoupled drugs. Studies were performed with livers of normal Wistar rats, and TR-/GT- Wistar rats with deficient drug excretion. The experiments showed that the parent drug HR 780 was slowly excreted into bile. In contrast, the excretion of the bile acid-conjugated HR 780 derivatives S 3554 (conjugated with cholate), S 3898 (conjugated with glycocholate), and S 4193 (conjugated with taurocholate) was rapid and very efficient in both groups of rat strains. The bile acid-conjugated HMG-CoA reductase inhibitors showed a 10 to 20 times higher affinity for the uptake systems of bile acids than the noncoupled parent drug compounds, and even higher affinities than the bile acids themselves. The cholate conjugate of HR 780 (compound S 3554) was shown to be a noncompetitive inhibitor of taurocholate uptake and a competitive inhibitor of sodium-independent cholate uptake (Ki = 1 mumol/L). Uptake of radiolabeled S 3554 into isolated rat hepatocytes was observed to be rapid, cell specific, saturable, energy dependent, and carrier mediated. However, the carrier for S 3554 uptake was found not to be the cloned Na(+)-dependent taurocholate cotransporting polypeptide Ntcp. Expression of this carrier cRNA in Xenopus laevis oocytes did not stimulate S 3554 uptake.
Recent advances in gastrointestinal oncology - updates and insights from the 2009 annual meeting of the American Society of Clinical Oncology
Authors: Milind Javle, Chung-Tsen Hsueh
Journal: Journal of Hematology & Oncology (2010)

We have reviewed the pivotal presentations related to gastrointestinal malignancies from 2009 annual meeting of the American Society of Clinical Oncology with the theme of "personalizing cancer care". We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. Adding trastuzumab to chemotherapy improved the survival of patients with advanced gastric cancer overexpressing human epidermal growth factor receptor 2. Gemcitabine plus cisplatin has become a new standard for first-line treatment of advanced biliary cancer. Octreotide LAR significantly lengthened median time to tumor progression compared with placebo in patients with metastatic neuroendocrine tumors of the midgut. Addition of oxaliplatin to fluoropyrimidines for preoperative chemoradiotherapy in patients with stage II or III rectal cancer did not improve local tumor response but increased toxicities. Bevacizumab did not provide additional benefit to chemotherapy in adjuvant chemotherapy for stage II or III colon cancer. In patients with resected stage II colon cancer, recurrence score estimated by multigene RT-PCR assay has been shown to provide additional risk stratification. In stage IV colorectal cancer, data have supported the routine use of prophylactic skin treatment in patients receiving antibody against epidermal growth factor receptor, and the use of upfront chemotherapy as initial management in patients with synchronous metastasis without obstruction or bleeding from the primary site.
Tumor Immunity in Small-Cell Lung Cancer
Authors: Robert Darnell
Journal: Journal of Clinical Oncology (2004)

An intriguing and potentially very important clinical question in human tumor immunity is addressed by Monstad et al [1] in the current issue of JCO. These authors explore the immune responses in a series of patients with small-cell lung cancer and correlate these correlations to clinical prognosis. To put this in perspective, some background is required. In the 1950s, Burnet [2] and Thomas [3] put forward a new idea, based on the recently discovered phenomenon of cellular immunity: if this branch of the immune system can recognize and kill cells infected with intracellular pathogens, it might also be able to do the same to cancer cells. The idea has not been readily testable in humans, because effective tumor immune responses would lead to suppression of cancer and, therefore, such patients would not be identifiable in the general population. A rare group of human neurologic diseases has provided an unexpected means to attempt to test Burnet’s and Thomas’s ideas regarding the existence of naturally occurring tumor immunity [4-6]. These disorders, known as paraneoplastic neurologic disorders, are believed to tie elements of often clinically occult tumor immune responses together with a severe clinical neurological disorder that brings patients to the attention of the physician-scientist. Systemic malignancies, not involving the nervous system, are believed to trigger the neurological disorders indirectly. That is, a number of tumor types have been found to express antigens normally expressed in neurons of the CNS. Presumably because of the immune privileged nature of such neurons (and their antigens) [7], the immune system is able to generate powerful reactions to the antigen expressed in the systemic tumor; this is associated in the majority of cases with at least partially effective tumor immune responses. A secondary set of events, poorly understood, are then believed to lead to compromise of the blood-brain barrier and immunologic privilege in the brain [8], leading the tumor immune response to spill over into an autoimmune attack in the brain. This rapidly leads patients to clinical attention, and hence the ability, working backward, to study the otherwise occult tumor immune response. Not all paraneoplastic neurologic disorders involve the CNS. Lambert-Eaton myasthenic syndrome is a disorder in which patients develop an unusual sort of muscle weakness, in which there is typically a temporary surge in muscle power during the first of a series of contractions. This disorder is associated with clinically occult small-cell lung cancer, and an immunologic link between the cancer and the neurologic disorder has been established by the finding
Health effects of passive smoking
Authors: S. CHINN, R. J RONA;, D. G COOK, D. P STRACHAN, I. M CAREY
Journal: Thorax (1999)

Intrathoracic extramedullary haematopoiesis (EMH) is a rare entity that is usually asymptomatic.A 44 year old man with alpha-thalassaemia is described who developed dyspnoea and massive left sided haemothorax.The haemoglobin disorder was established by Hgb H staining and haemoglobin electrophoretic studies.The DNA analysis revealed it to be a case of double heterozygous terminal codon mutation with the genotype CS / T .Computed tomographic scanning and magnetic resonance imaging of the thorax showed multiple paravertebral masses which were found by thoracoscopic biopsy to be extramedullary haematopoiesis.Although no additional sclerosing pleurodesis or low dose radiation therapy was given, the lung expanded well and there has been no recurrence of haemothorax to date.
The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice
Authors: Arjen R Mensenkamp, Marja J.A van Luyn, Rick Havinga, Bas Teusink, Ian J Waterman, Christopher J Mann, Baukje M Elzinga, Henkjan J Verkade, Victor A Zammit, Louis M Havekes, Carol C Shoulders, Folkert Kuipers
Journal: Journal of Hepatology (2004)
UBIQUITIN-DEPENDENT REGULATION OF THE SYNAPSE
Authors: Aaron DiAntonio, Linda Hicke
Journal: Annual Review of Neuroscience (2004)

Posttranslational modification of cellular proteins by the covalent attachment of ubiquitin regulates protein stability, activity, and localization. Ubiquitination is rapid and reversible and is a potent mechanism for the spatial and temporal control of protein activity. By sculpting the molecular composition of the synapse, this versatile posttranslational modification shapes the pattern, activity, and plasticity of synaptic connections. Synaptic processes regulated by ubiquitination, as well as ubiquitination enzymes and their targets at the synapse, are being identified by genetic, biochemical, and electrophysiological analyses. This work provides tantalizing hints that neuronal activity collaborates with ubiquitination pathways to regulate the structure and function of synapses.
PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI
Authors: Raj S. Kasthuri, Sam L. Glover, William Jonas, Troy McEachron, Rafal Pawlinski, Gowthami M. Arepally, Nigel S. Key, Nigel Mackman
Journal: Blood (2012)
Excessive centrosome abnormalities without ongoing numerical chromosome instability in a Burkitt's lymphoma.
Authors: Stefan Duensing, Benjamin H Lee, Paola Cin, Karl Münger
Journal: Molecular Cancer (2003)

Numerical and structural centrosome abnormalities are detected in various human malignancies and have been implicated in the formation of multipolar mitoses, chromosome missegregation, and chromosomal instability. Despite this association between centrosome abnormalities and cancerous growth, a causative role of centrosome aberrations in generating chromosomal instability and aneuploidy has not been universally established. We report here excessive numerical and structural centrosome abnormalities in a malignant Burkitt's lymphoma harboring the characteristic t(8;14) chromosomal translocation. Using conventional karyotyping and fluorescence in situ hybridization (FISH), we detected no signs of ongoing numerical chromosome instability, although the tumor displayed sporadic multipolar metaphases. These findings demonstrate that centrosome abnormalities are not a universal surrogate marker for chromosomal instability in malignant tumors. Moreover, our results suggest a model in which additional cellular alterations may be required to promote centrosome-related mitotic defects in tumor cells.
Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C
Authors: Paula Bonorino, Muhammad Ramzan, Xavier Camous, Tania Dufeu-Duchesne, Marie-Ange Thélu, Nathalie Sturm, Aurélie Dariz, Christiane Guillermet, Martine Pernollet, Jean-Pierre Zarski, Patrice N. Marche, Vincent Leroy, Evelyne Jouvin-Marche
Journal: Journal of Hepatology (2009)
The relationship between plasma psoralen concentration and psoralen-UVA erythema
Authors: JANET MCLELLAND, CHRISTINE FISHER, P. M. FARR, B. L. DIFFEY, N. H. COX
Journal: British Journal of Dermatology (1991)

The plasma 8-methoxypsoralen (8-MOP) concentration was measured in 60 patients commencing psoralen photochemotherapy (PUVA). At the time of blood sampling each patient was phototested using a series of 10 exposures to UVA. The resulting erythema was measured objectively 72 h after irradiation and dose-response curves for psoralen-UVA erythema were constructed. Although the dose of 8-MOP was calculated according to body weight, patients receiving 30 mg of 8-MOP had a significantly lower mean plasma concentration than those receiving higher doses. There was no significant correlation between plasma 8-MOP concentration and minimal phototoxic dose, either estimated visually or calculated from the dose-response curves. However the slope of the dose-response curve showed significant correlation with plasma 8-MOP concentration. The variation between patients in the rate of increase of the erythemal response, but not the variation in threshold sensitivity, can be explained by difference in plasma psoralen concentration.
Combined percutaneous and endoscopic procedures for bile duct obstruction.
Authors: D F Martin
Journal: Gut (1994)

Leading articleCombined percutaneous and endoscopic procedures for bile duct obstruction Deep cannulation of the bile duct is essential for the successful treatment of biliary obstruction.Even the most experienced endoscopist cannot always achieve this.Identifiable causes of failure include previous gastric surgery and periampullary diverticulum,l but often it is
Simultaneous Control of Hyperglycemia and Oxidative Stress Normalizes Endothelial Function in Type 1 Diabetes
Authors: Antonio Ceriello, Sudhesh Kumar, Ludovica Piconi, Katerine Esposito, Dario Giugliano
Journal: Diabetes Care (2007)

Previous studies have shown that in type 1 diabetes endothelial dysfunction persists even when glycemia is normalized. Moreover, oxidative stress has recently been demonstrated to be the mediator of hyperglycemia-induced endothelial dysfunction.Thirty-six type 1 diabetic patients and 12 control subjects were enrolled. The diabetic patients were divided into three groups. The first group was treated for 24 h with insulin, achieving a near-normalization of glycemia. After 12 h of this treatment, vitamin C was added for the remaining 12 h. The second group was treated for 24 h with vitamin C. After 12 h of this treatment, insulin was started, with achievement of near-normalization of glycemia for the remaining 12 h. The third group was treated for 24 h with both vitamin C and insulin, achieving near-normalization of glycemia.Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. However, a combination of insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels.This study suggests that long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations in endothelial cells, which may contribute to endothelial dysfunction by increased oxidative stress even when hyperglycemia is normalized.
Spotlight on measles 2010: Measles outbreak among travellers returning from a mass gathering, Germany, September to October 2010
Authors: G Pfaff, D Lohr, S Santibanez, A Mankertz, U van Treeck, K Schönberger, W Hautmann
Journal: Eurosurveillance (2010)

Binary file ES_Abstracts_Final_ECDC.txt matches
Adolf Bingel's blinded, controlled comparison of different anti-diphtheritic sera in 1918
Authors: Ulrich Tröhler
Journal: Journal of the Royal Society of Medicine (2011)

With the uptake of serum treatment for diphtheria from the end of the 19th century onwards, deaths from the disease fell dramatically,1 albeit, less dramatically in countries, such as the UK, in which serum treatment had not been adopted wholeheartedly.2 The development of serum therapy of humans – in a race between the Berlin Institute for Infectious Diseases and Emile Roux and his colleagues at the Pasteur Institute in Paris – led to the award of the first ever Nobel Prize in physiology or medicine, in 1901, to Emil Behring. This illustrated that there was wide acceptance that anti-diphtheritic serum was effective.
Invariant Chain Controls the Activity of Extracellular Cathepsin L
Authors: Edda Fiebiger, René Maehr, José Villadangos, Ekkehard Weber, Ann Erickson, Elizabeth Bikoff, Hidde L. Ploegh, Ana-Maria Lennon-Duménil
Journal: The Journal of Experimental Medicine (2002)

Secretion of proteases is critical for degradation of the extracellular matrix during an inflammatory response. Cathepsin (Cat) S and L are the major elastinolytic cysteine proteases in mouse macrophages. A 65 amino acid segment of the p41 splice variant (p41(65aa)) of major histocompatibility complex class II-associated invariant chain (Ii) binds to the active site of CatL and permits the maintenance of a pool of mature enzyme in endosomal compartments of macro-phages and dendritic cells (DCs). Here we show that interaction of p41(65aa) with mature CatL allows extracellular accumulation of the active enzyme. We detected mature CatL as a complex with p41(65aa) in culture supernatants from antigen-presenting cells (APCs). Extracellular accumulation of mature CatL is up-regulated by inflammatory stimuli as observed in interferon (IFN)-gamma-treated macrophages and lipopolysaccharide (LPS)-activated DCs. Despite the neutral pH of the extracellular milieu, released CatL associated with p41(65aa) is catalytically active as demonstrated by active site labeling and elastin degradation assays. We propose that p41(65aa) stabilizes CatL in the extracellular environment and induces a local increase in the concentration of matrix-degrading enzymes during inflammation. Through its interaction with CatL, Ii may therefore control the migratory response of APCs and/or the recruitment of effectors of the inflammatory response.
Y-Chromosome Mismatch Distributions in Europe
Authors: Luísa Pereira, Isabelle Dupanloup, Zoë H. Rosser, Mark A. Jobling, Guido Barbujani
Journal: Molecular Biology and Evolution (2001)

Ancient demographic events can be inferred from the distribution of pairwise sequence differences (or mismatches) among individuals. We analyzed a database of 3,677 Y chromosomes typed for 11 biallelic markers in 48 human populations from Europe and the Mediterranean area. Contrary to what is observed in the analysis of mitochondrial polymorphisms, Tajima's test was insignificant for most Y-chromosome samples, and in 47 populations the mismatch distributions had multiple peaks. Taken at face value, these results would suggest either (1) that the size of the male population stayed essentially constant over time, while the female population size increased, or (2) that different selective regimes have shaped mitochondrial and Y-chromosome diversity, leading to an excess of rare alleles only in the mitochondrial genome. An alternative explanation would be that the 11 variable sites of the Y chromosome do not provide sufficient statistical power, so a comparison with mitochondrial data (where more than 200 variable sites are studied in Europe) is impossible at present. To discriminate between these possibilities, we repeatedly analyzed a European mitochondrial database, each time considering only 11 variable sites, and we estimated mismatch distributions in stable and growing populations, generated by simulating coalescent processes. Along with theoretical considerations, these tests suggest that the difference between the mismatch distributions inferred from mitochondrial and Y-chromosome data are not a statistical artifact. Therefore, the observed mismatch distributions appear to reflect different underlying demographic histories and/or selective pressures for maternally and paternally transmitted loci.
Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice
Authors: Arash Shahangian, Edward K. Chow, Xiaoli Tian, Jason R. Kang, Amir Ghaffari, Su Y. Liu, John A. Belperio, Genhong Cheng, Jane C. Deng
Journal: Journal of Clinical Investigation (2009)

Influenza-related complications continue to be a major cause of mortality worldwide. Due to unclear mechanisms, a substantial number of influenza-related deaths result from bacterial superinfections, particularly secondary pneumococcal pneumonia. Here, we report what we believe to be a novel mechanism by which influenza-induced type I IFNs sensitize hosts to secondary bacterial infections. Influenza-infected mice deficient for type I IFN-alpha/beta receptor signaling (Ifnar-/- mice) had improved survival and clearance of secondary Streptococcus pneumoniae infection from the lungs and blood, as compared with similarly infected wild-type animals. The less effective response in wild-type mice seemed to be attributable to impaired production of neutrophil chemoattractants KC (also known as Cxcl1) and Mip2 (also known as Cxcl2) following secondary challenge with S. pneumoniae. This resulted in inadequate neutrophil responses during the early phase of host defense against secondary bacterial infection. Indeed, influenza-infected wild-type mice cleared secondary pneumococcal pneumonia after pulmonary administration of exogenous KC and Mip2, whereas neutralization of Cxcr2, the common receptor for KC and Mip2, reversed the protective phenotype observed in Ifnar-/- mice. These data may underscore the importance of the type I IFN inhibitory pathway on CXC chemokine production. Collectively, these findings highlight what we believe to be a novel mechanism by which the antiviral response to influenza sensitizes hosts to secondary bacterial pneumonia.
HMGCoA reductase inhibition reverses myocardial fibrosis and diastolic dysfunction through AMP-activated protein kinase activation in a mouse model of metabolic syndrome
Authors: Nerea Hermida, Andreas Markl, Julien Hamelet, Tim Van Assche, Annelies Vanderper, Paul Herijgers, Marc van Bilsen, Denise Hilfiker-Kleiner, Gauthier Noppe, Christophe Beauloye, Sandrine Horman, Jean-Luc Balligand
Journal: Cardiovascular Research (2013)

AimsThe metabolic syndrome (MS) leads to myocardial fibrosis (MF) and diastolic dysfunction. Statins have proven beneficial effects in MS, but their impact on cardiac remodelling is uncertain. We examined the effects and mechanisms of chronic statin treatment on cardiac remodelling, e.g. fibrosis and diastolic properties.
Transesophageal Echocardiography During Ventricular Fibrillation
Authors: Tomás F. Cianciulli, Daniel E. Ferreiro, Daniel G. Davolos, María C. Saccheri, Jorge A. Lax, Horacio A. Prezioso, Luis A. Vidal
Journal: Circulation (2009)

udden cardiac death is most frequently caused by spon- taneous onset of ventricular fibrillation (VF), during which the rhythmic heart contractions transform into chaotic, vermiform, and inefficient activity of the myocardium while the pulsatile pulmonary and systemic blood flow circuits stop.Little information is available on the anatomical and hemodynamic changes that occur during VF.These changes could be seen in humans with transesophageal echocardiography (TEE).