tbuckley/cabot-search huggingface dataset:
GLP-1 Effects on Islets: Hormonal, Neuronal, or Paracrine?
Authors: Marc Y. Donath, Rémy Burcelin
Journal: Diabetes Care (2013)

According to the classical incretin concept, glucagon-like peptide (GLP)-1 is viewed as a hormone produced in the intestinal L cells and acting via the circulation on satiety in the brain, gut motility, and insulin and glucagon secretion in the pancreatic islet. However, in contrast to typical hormones, plasma levels of GLP-1 are relatively low with a very short half-life. Furthermore, GLP-1 is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4) in the vicinity of L cells within <1 min from the secretion of the gut peptide (1,2). This rapid metabolism of GLP-1 raises questions about how its effects are mediated on target organs such as pancreatic β-cells. In this review, we will discuss possible alternative pathways for the incretin effect on pancreatic islet. These involve L cell–derived GLP-1 via neuronal activation and α-cell–derived GLP-1 via auto/paracrine effects. Of note, GLP-1 is not acting alone, and its effect can be modulated by other factors including GIP. Since no data are available yet in the present context, we have limited this review to GLP-1.

### GLP-1 in the gut-to-brain-to-periphery axis for the control of glucose metabolism

Recent rodent data show that GLP-1 can induce its metabolic actions by interacting with its receptors in extrapancreatic locations such as the gut to activate the submucosal and the myenteric nervous plexi (3,4) and the brain, which then transmit the signal to peripheral tissues (5) within minutes from the absorption of glucose and lipids. The final aim of this axis is to anticipate the breakthrough of the nutrients into the blood and their better handling. Indeed, GLP-1 secreted from L cells can influence brain neuronal activities via an alternative neural pathway initiated by sensors in the hepatic portal region (6–8). Thereby, the vagus nerve transmits the metabolic information to the nucleus tractus solitarii in the brain stem, which relays the glucose signal to hypothalamic …
Gene expression profiling–based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants
Authors: Ronald W. Stam, Pauline Schneider, Jill A. P. Hagelstein, Marieke H. van der Linden, Dominique J. P. M. Stumpel, Renee X. de Menezes, Paola de Lorenzo, Maria G. Valsecchi, Rob Pieters
Journal: Blood (2009)
Is Observation Dead in Follicular Lymphoma? No, But the Apoptosis Pathway Has Been Activated
Authors: Richard I. Fisher, Nadia Khan
Journal: Journal of the National Comprehensive Cancer Network (2015)

Follicular lymphoma (FL), the most common indolent type of non-Hodgkin's lymphoma, presents with a highly variable clinical course and affects the overall survival (OS) of patients. Although observation has been adopted widely by clinicians in the management of patients with FL, the benefits of early treatment must be reviewed in light of the significant progress made in the treatment of symptomatic or higher-tumor-burden FL. When treatment is indicated, a variety of combination chemotherapeutic regimens have proven efficacy and have shown improvements in both progression-free and event-free survival, and the addition of rituximab to these regimens has shown a statistically significant improvement in OS. Additionally, single-agent rituximab has been added to the possible therapeutic options for patients with low-tumor-burden FL. Although a paucity of clinical data exists on the upfront treatment of the low-tumor-burden population, the question of whether early treatment, especially with the newer rituximab-containing chemotherapy regimens, would improve OS is thought-provoking. Furthermore, novel targeted therapies with tolerable side effect profiles are rapidly advancing in the treatment of non-Hodgkin's lymphoma. The future for patients with low-tumor-burden FL is brighter than ever before.
Lung oxidant injury in a model of lung storage and extended reperfusion.
Authors: N A Christie, D E Smith, K N Decampos, A S Slutsky, G A Patterson, A K Tanswell
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Donor lungs for transplantation are susceptible to "preservation" injury during both storage and postimplantation reperfusion. We investigated whether lung dysfunction seen after storage and reperfusion was associated with any biochemical hallmarks of direct cellular oxidant injury to lipid, protein, or DNA. Heart/lung blocks were extracted from adult rats following pulmonary vascular flush. Lungs were either perfused immediately ex vivo for 2 h with deoxygenated venous rat blood or were stored at 10 degrees C for 13 h before perfusion. Stored lungs had increased airway pressure, pulmonary vascular shunt fraction, wet/dry weight ratio, and parenchymal hemorrhage after perfusion but no change in pulmonary artery pressure compared with immediately perfused lungs. Hypothermic storage caused no biochemical changes in lung tissue. Perfusion of fresh or stored lungs resulted in lipid peroxidation and loss of nonprotein reduced sulfhydryls; sulfhydryl loss was threefold higher in lungs stored before perfusion compared with freshly perfused lungs. Reperfusion of stored, not fresh, lungs was associated with DNA damage. No loss of protein sulfhydryls occurred following lung perfusion. We conclude that DNA damage, loss of reduced nonprotein sulfhydryls, and lipid peroxidation during reperfusion of stored lungs may be responsible for physiologic lung dysfunction.
Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: correlation with disease progression
Authors: S. Miyagawa, M. Amagai, T. Iida, Y. Yamamoto, T. Nishikawa, T. Shirai
Journal: British Journal of Dermatology (1999)

Journal Article Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: correlation with disease progression Get access S. Miyagawa, S. Miyagawa Department of Dermatology, Nara Medical University, Kashihara City, Nara 634, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Amagai, M. Amagai Department of Dermatology, Keio University School of Medicine, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Iida, T. Iida Department of Dermatology, Nara Medical University, Kashihara City, Nara 634, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Yamamoto, Y. Yamamoto Department of Dermatology, Nara Medical University, Kashihara City, Nara 634, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Nishikawa, T. Nishikawa Department of Dermatology, Keio University School of Medicine, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Shirai T. Shirai Department of Dermatology, Nara Medical University, Kashihara City, Nara 634, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 6, 1 December 1999, Pages 1084–1087, https://doi.org/10.1046/j.1365-2133.1999.03209.x Published: 01 December 1999
Identifying Sarcomere Gene Mutations in Hypertrophic Cardiomyopathy
Authors: Christine E. Seidman, J.G. Seidman
Journal: Circulation Research (2011)

This review provides an historical and personal perspective on the discovery of genetic causes for hypertrophic cardiomyopathy (HCM). Extraordinary insights by physicians who initially detailed remarkable and varied manifestations of the disorder, collaboration among multidisciplinary teams with skills in clinical diagnostics and molecular genetics, and hard work by scores of trainees solved the etiologic riddle of HCM and unexpectedly demonstrated mutations in sarcomere protein genes as the cause of disease. In addition to celebrating 20 years of genetic research in HCM, this article serves as an introductory overview to a thematic review series that will present contemporary advances in the field of hypertrophic heart disease. Through the continued application of advances in genetic methodologies, combined with biochemical and biophysical analyses of the consequences of human mutations, fundamental knowledge about HCM and sarcomere biology has emerged. Expanding research to elucidate the mechanisms by which subtle genetic variation in contractile proteins remodel the human heart remains an exciting opportunity, one with considerable promise to provide new strategies to limit or even prevent HCM pathogenesis.
Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort
Authors: Felix J.F. Herth, Marc Noppen, Arschang Valipour, Sylvie Leroy, Jean-Michel Vergnon, Joachim H. Ficker, Jim J. Egan, Stefano Gasparini, Carlos Agusti, Debby Holmes-Higgin, Armin Ernst
Journal: European Respiratory Journal (2012)

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n=111) or medical management (n=60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean± sd change in forced expiratory volume in 1 s (7±20% versus 0.5±19%; p=0.067), cycle ergometry (2±14 W versus -3±10 W; p=0.04) and St George’s Respiratory Questionnaire (-5±14 points versus 0.3±13 points; p=0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean± sd lobar volume reduction of -80±30% and &gt;50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.
Idiopathic bile acid catharsis.
Authors: E H Thaysen, L Pedersen
Journal: Gut (1976)

In the course of extensive routine screening for bile acid malabsorption a few patients were detected in whom chronic diarrhoea was apparently induced by excess bile acid loss which was neither associated with demonstrable conventional ileopathy nor with any other disorder allied to diarrhoea. In three patients subjected to scrutiny the results obtained were in harmony with a concept of idiopathic bile acid catharsis. Ingestion of cholestyramine was followed by immediate relief, but the diarrhoea recurred whenever this treatment was withdrawn. It it suggested that idiopathic bile acid catharsis should be suspected in patients with unexplained chronic diarrhoea and especially in those with a diagnosis of irritable colon with diarrhoea.
Evolution of Duplicated -Globin Genes and the Structural Basis of Hemoglobin Isoform Differentiation in Mus
Authors: A. M. Runck, H. Moriyama, J. F. Storz
Journal: Molecular Biology and Evolution (2009)

The functional diversification of multigene families may be strongly influenced by mechanisms of concerted evolution such as interparalog gene conversion. The β-globin gene family of house mice (genus Mus) represents an especially promising system for evaluating the effects of gene conversion on the functional divergence of duplicated genes. Whereas the majority of mammalian species possess tandemly duplicated copies of the adult β-globin gene that are identical in sequence, natural populations of house mice are often polymorphic for distinct two-locus haplotypes that differ in levels of functional divergence between duplicated β-globin genes, HBB-T1 and HBB-T2. Here, we use a phylogenetic approach to unravel the complex evolutionary history of the HBB-T1 and HBB-T2 paralogs in a taxonomically diverse set of species in the genus Mus. The main objectives of this study were 1) to reconstruct the evolutionary history of the different HBB haplotypes of house mice, 2) to assess the role of recombinational exchange between HBB-T1 and HBB-T2 in promoting concerted evolution, 3) to assess the role of recombinational exchange between HBB-T1 and HBB-T2 in creating chimeric genes, and 4) to assess the structural basis of hemoglobin isoform differentiation in species that possess distinct HBB paralogs. Results of our phylogenetic survey revealed that the HBB-T1 and HBB-T2 genes in different species of Mus exhibit the full range of evolutionary outcomes with respect to levels of interparalog divergence. At one end of the spectrum, the two identical HBB paralogs on the Hbbs haplotype (shared by Mus domesticus, Mus musculus, and Mus spretus) represent a classic example of concerted evolution. At the other end of the spectrum, the two distinct HBB paralogs on the Hbbd, Hbbp, Hbbw1, and Hbbw2 haplotypes (shared by multiple species in the subgenus Mus) show no trace of gene conversion and are distinguished by a number of functionally important amino acid substitutions. Because the possession of distinct HBB paralogs expands the repertoire of functionally distinct hemoglobin isoforms that can be synthesized during fetal development and postnatal life, variation in the level of functional divergence between HBB-T1 and HBB-T2 may underlie important physiological variation within and among species.
Polo-like Kinase Plk2 Is an Epigenetic Determinant of Chemosensitivity and Clinical Outcomes in Ovarian Cancer
Authors: Nelofer Syed, Helen M. Coley, Jalid Sehouli, Dominique Koensgen, Alexander Mustea, Peter Szlosarek, Iain McNeish, Sarah P. Blagden, Peter Schmid, David P. Lovell, Eleftheria Hatzimichael, Tim Crook
Journal: Cancer Research (2011)

Resistance to platinum- and taxane-based chemotherapy remains a major clinical impediment to effective management of epithelial ovarian cancer (EOC). To gain insights into resistance mechanisms, we compared gene and confirmed expression patterns of novel EOC cell lines selected for paclitaxel and carboplatin resistance. Here, we report that resistance can be conferred by downregulation of the Polo-like kinase Plk2. Mechanistic investigations revealed that downregulation occurred at the level of transcription via associated DNA methylation of the CpG island in the Plk2 gene promoter in cell lines, primary tumors, and patient sera. Inhibitory RNA (RNAi)-mediated knockdown and ectopic overexpression established a critical functional role for Plk2 in determining apoptotic sensitivity to paclitaxel and carboplatin. In drug-resistant human EOC cell lines, Plk2 promoter methylation varied with the degree of drug resistance and transcriptional silencing of the promoter. RNAi-dependent knockdown of Plk2 abrogated G(2)-M cell-cycle blockade by paclitaxel, conferring resistance to both paclitaxel and platinum. Conversely, ectopic expression of Plk2 restored sensitivity to G(2)-M cell-cycle blockade and cytotoxicity triggered by paclitaxel. In clinical cases, DNA methylation of the Plk2 CpG island in tumor tissue was associated with a higher risk of relapse in patients treated postoperatively with carboplatin and paclitaxel (P = 0.003). This trend was also reflected in the analysis of matched serum samples. Taken together, our results implicate Plk2 as a clinically important determinant of chemosensitivity, in support of the candidacy of Plk2 as a theranostic marker to inform EOC management.
Preferences for place of death if faced with advanced cancer: a population survey in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain
Authors: B Gomes, I J Higginson, N Calanzani, J Cohen, L Deliens, B A Daveson, D Bechinger-English, C Bausewein, P L Ferreira, F Toscani, A Meñaca, M Gysels, L Ceulemans, S T Simon, H R W Pasman, G Albers, S Hall, F E M Murtagh, D F Haugen, J Downing, J Koffman, F Pettenati, S Finetti, B Antunes, R Harding
Journal: Annals of Oncology (2012)
Dispatcher-Assisted Cardiopulmonary Resuscitation
Authors: Miranda Lewis, Benjamin A. Stubbs, Mickey S. Eisenberg
Journal: Circulation (2013)

Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR), in which 9-1-1 dispatchers provide CPR instructions over the telephone, has been shown to nearly double the rate of bystander CPR. We sought to identify factors that hampered the identification of cardiac arrest by 9-1-1 dispatchers and prevented or delayed the provision of dispatcher-assisted CPR chest compressions.We reviewed dispatch recordings for 476 out-of-hospital cardiac arrests occurring between January 1, 2011, and December 31, 2011. We found that the dispatcher correctly identified cardiac arrest in 80% of reviewed cases and 92% of cases in which they were able to assess patient consciousness and breathing. The median time to recognition of the arrest was 75 seconds. Chest compressions following dispatcher-assisted CPR instructions occurred in 62% of cases when the dispatcher had the opportunity to asses for consciousness and breathing and bystander CPR was not already started. The median time to first dispatcher-assisted CPR chest compression was 176 seconds.Dispatchers are able to accurately diagnose cardiac arrest over the telephone, but recognition is likely not possible in all circumstances. In some cases, recognition of cardiac arrest may be improved through training in the detection of agonal respirations. Delays in the delivery of dispatcher-assisted CPR chest compressions are common and are attributable to a mixture of dispatcher behavior and factors beyond the control of the dispatcher. Performance standards for the successful and quick recognition of cardiac arrest and delivery of first chest compressions should be adopted as metrics against which emergency medical services systems can measure their performance.
Effect of chronic 5-lipoxygenase inhibition on airway hyperresponsiveness in asthmatic subjects.
Authors: A R Fischer, C A McFadden, R Frantz, W M Awni, J Cohn, J M Drazen, E Israel
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The leukotrienes are known bronchoactive agonists with potential proinflammatory effects that may be involved in mediating airway hyperresponsiveness. We investigated the effects of zileuton, an inhibitor of 5-lipoxygenase (5-LO), on airway responsiveness to cold, dry air in patients with moderate asthma. A group of 10 asthmatic patients underwent cold, dry air hyperventilation challenge; challenges were performed before drug treatment and 1 to 10 d after the completion of treatment with study drugs. The cold air minute ventilation required to cause a 15% decrease in FEV1 (PD15 VE) increased by 58% compared with the response before treatment, 1 to 10 d after the completion of 13 wk of treatment with zileuton. The geometric mean (geometric mean/SEM and geometric mean x SEM) PD15 VE increased from 24.5 (20.4, 29.5) L/min to 38.8 (34.7, 43.7) L/min (p = 0.01). Zileuton treatment inhibited 5-LO as measured ex vivo by ionophore-stimulated LTB4 levels in whole blood. In four of seven subjects, LTB4 levels before zileuton ingestion fell from 110.88 +/- 25.42 to 5.40 +/- 1.95 ng/ml 2 h post-zileuton dosing (p = 0.02, pre- versus 2 h postzileuton ingestion). Consistent with the short half-life of zileuton, 6 h postzileuton dosing the ionophore-stimulated, LTB4 levels in whole blood had increased to 89.68 +/- 35.54 ng/ml (p = 0.41, pre- versus 6 h postzileuton ingestion). Based on the first-order kinetics of zileuton, its effect on 5-LO activity should have been dissipated less than 16 h postingestion. Thus, chronic zileuton treatment decreased airway hyperresponsiveness as determined by reactivity to cold, dry air.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of Activating <i>Fibroblast Growth Factor Receptor 3</i> Mutations in the Development of Bladder Tumors
Authors: Karsten Zieger, Lars Dyrskjøt, Carsten Wiuf, Jens L. Jensen, Claus L. Andersen, Klaus Møller-Ernst Jensen, Torben Falck Ørntoft
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Bladder tumors develop through different molecular pathways. Recent reports suggest activating mutations of the fibroblast growth factor receptor 3 (FGFR3) gene as marker for the “papillary” pathway with good prognosis, in contrast to the more malignant “carcinoma in situ” (CIS) pathway. The aim of this clinical follow-up study was to investigate the role of FGFR3 mutations in bladder cancer development in a longitudinal study. Experimental Design: We selected 85 patients with superficial bladder tumors, stratified into early (stage Ta/grade 1-2, n = 35) and more advanced (either stage T1 or grade 3, n = 50) developmental stages. The patients were followed prospectively, and metachronous tumors were included. We did screening for FGFR3 and TP53 mutations by direct bidirectional sequencing and for genome-wide molecular changes with microarray technology. Results: A total of 43 of 85 cases (51%) showed activating mutations of FGFR3. The mutations were associated with papillary tumors of early developmental stage. However, after stratifying for developmental stage, FGFR3-mutated tumors showed the same malignant potential as wild-type tumors. Tumors with concomitant CIS were generally FGFR3 wild type. They were characterized by different patterns of chromosomal changes and gene expression signatures compared with FGFR3-mutated tumors, indicating different molecular pathways. Conclusions: FGFR3 mutations seem to have a central role in the early development of papillary bladder tumors. These tumors follow a common molecular pathway, which is different from tumors with concomitant CIS. FGFR3 mutations do not seem to play a role in bladder cancer progression.
Hypnotherapy for alopecia areata
Authors: P.V. Harrison, P. Stepanek
Journal: British Journal of Dermatology (1991)

Journal Article Hypnotherapy for alopecia areata Get access P.V. Harrison, P.V. Harrison Department of Dermatology, Queen Victoria Hospital, Morecambe LA4 5NN, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. Stepanek P. Stepanek Department of Dermatology, Queen Victoria Hospital, Morecambe LA4 5NN, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 5, 1 May 1991, Pages 509–510, https://doi.org/10.1111/j.1365-2133.1991.tb00644.x Published: 01 May 1991