tbuckley/cabot-search huggingface dataset:
Asthma exacerbations {middle dot} 4: Prevention
Authors: J M FitzGerald, P G Gibson
Journal: Thorax (2006)

Asthma exacerbations are common. They account for a significant morbidity and contribute a disproportionate amount to the cost of asthma management. The optimal strategies for the prevention of asthma exacerbations include the early introduction of anti-inflammatory treatment-most commonly, low dose inhaled corticosteroids. This should be coupled with a structured education programme which has a written action plan as an integral component. Where patients continue to be poorly controlled, the addition of a long acting beta agonist should be considered. The latter should not be used as monotherapy and should always be used with inhaled corticosteroids. Atopic patients with a history of repeated exacerbations, especially if they are steroid dependent and with a raised IgE, may be considered as potential candidates for omalizumab. In the early stages of an asthma exacerbation, doubling the dose of inhaled corticosteroids has been shown to be ineffective. The ideal strategy for the management of worsening asthma in patients on combination treatment, especially salmeterol and fluticasone, is uncertain. There is an emerging body of evidence for strategies on how to prevent progression to an exacerbation in patients taking a combination of budesonide and formoterol.
Long-term efficacy of topical tacrolimus on oral lesions of chronic graft-versus-host disease
Authors: J.-C. Fricain, V. Sibaud, N. Swetyenga, R. Tabrizi, F. Campana, A. Taïeb
Journal: British Journal of Dermatology (2007)

Journal Article Long‐term efficacy of topical tacrolimus on oral lesions of chronic graft‐versus‐host disease Get access J.‐C. Fricain, J.‐C. Fricain Departments of Odontology and †Maxillofacial Surgery, Pellegrin University Hospital, Bordeaux, France *Department of Dermatology, Saint André University Hospital, Bordeaux, France ‡Department of Haematology, Haut Levêque University Hospital, Pessac, France E‐mail: jean‐christophe.fricain@biophys.u‐bordeaux2.fr Search for other works by this author on: Oxford Academic Google Scholar V. Sibaud, V. Sibaud Departments of Odontology and †Maxillofacial Surgery, Pellegrin University Hospital, Bordeaux, France *Department of Dermatology, Saint André University Hospital, Bordeaux, France ‡Department of Haematology, Haut Levêque University Hospital, Pessac, France E‐mail: jean‐christophe.fricain@biophys.u‐bordeaux2.fr Search for other works by this author on: Oxford Academic Google Scholar N. Swetyenga, N. Swetyenga Departments of Odontology and †Maxillofacial Surgery, Pellegrin University Hospital, Bordeaux, France *Department of Dermatology, Saint André University Hospital, Bordeaux, France ‡Department of Haematology, Haut Levêque University Hospital, Pessac, France E‐mail: jean‐christophe.fricain@biophys.u‐bordeaux2.fr Search for other works by this author on: Oxford Academic Google Scholar R. Tabrizi, R. Tabrizi Departments of Odontology and †Maxillofacial Surgery, Pellegrin University Hospital, Bordeaux, France *Department of Dermatology, Saint André University Hospital, Bordeaux, France ‡Department of Haematology, Haut Levêque University Hospital, Pessac, France E‐mail: jean‐christophe.fricain@biophys.u‐bordeaux2.fr Search for other works by this author on: Oxford Academic Google Scholar F. Campana, F. Campana Departments of Odontology and †Maxillofacial Surgery, Pellegrin University Hospital, Bordeaux, France *Department of Dermatology, Saint André University Hospital, Bordeaux, France ‡Department of Haematology, Haut Levêque University Hospital, Pessac, France E‐mail: jean‐christophe.fricain@biophys.u‐bordeaux2.fr Search for other works by this author on: Oxford Academic Google Scholar A. Taïeb A. Taïeb Departments of Odontology and †Maxillofacial Surgery, Pellegrin University Hospital, Bordeaux, France *Department of Dermatology, Saint André University Hospital, Bordeaux, France ‡Department of Haematology, Haut Levêque University Hospital, Pessac, France E‐mail: jean‐christophe.fricain@biophys.u‐bordeaux2.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 3, 1 March 2007, Pages 588–590, https://doi.org/10.1111/j.1365-2133.2006.07679.x Published: 01 March 2007
CA 19-9 Related Tumor Growth Rate After First Line Chemotherapy of Advanced Pancreatic Cancer
Authors: Colloca Giuseppe, Venturino Antonella, Coccorullo Zaira, Guarneri Domenico, Caltabiano Graziano, Addamo Gianfranco, Ratti Riccardo, Repetto Lazzaro
Journal: Annals of Oncology (2014)
Frontline extended surgery is associated with improved survival in retroperitoneal low- to intermediate-grade soft tissue sarcomas
Authors: A. Gronchi, R. Miceli, C. Colombo, S. Stacchiotti, P. Collini, L. Mariani, C. Sangalli, S. Radaelli, R. Sanfilippo, M. Fiore, P.G. Casali
Journal: Annals of Oncology (2011)
Paradoxically Enhanced Endothelin-B Receptor–Mediated Vasoconstriction in Conscious Old Monkeys
Authors: Kuniya Asai, Raymond K. Kudej, Gen Takagi, Amelia B. Kudej, Filipinas Natividad, You-Tang Shen, Dorothy E. Vatner, Stephen F. Vatner
Journal: Circulation (2001)

Background —We investigated the effects of aging on the responses to endothelin (ET) in conscious old (19.8±0.6 years) and young adult (6.8±0.3 years) monkeys and compared these results with those of other vasoconstrictors, eg, phenylephrine (PE) and angiotensin II (Ang II). Methods and Results —The monkeys ( Macaca fascicularis ) were chronically instrumented. Baseline total peripheral resistance (TPR) was not different between the 2 groups. As expected, TPR rose less ( P &lt;0.05) with PE (5 μg/kg) in old monkeys (34±3%) than in young monkeys (57±6%); TPR also rose less with Ang II. Surprisingly, TPR rose more ( P &lt;0.05) with endothelin-1 (ET-1, 25 ng · kg −1 · min −1 ) in old monkeys (36±6%) than in young monkeys (10±2%). An ET B receptor agonist, sarafotoxin (S6c, 30 ng · kg −1 · min −1 ) was administered in the presence of an ET A receptor antagonist, BQ-123 (1 mg/kg). Under these conditions, TPR increased more ( P &lt;0.05) in old monkeys (59±10%) than in young monkeys (31±4%). In the presence of nitric oxide synthase (NOS) inhibition with N W -nitro- l -arginine methyl ester (60 mg/kg), vasoconstriction induced by S6c no longer differed with age, because it was enhanced in young monkeys ( P &lt;0.05) (68±9% versus 31±4%) but not in old monkeys (58±6% versus 59±10%). Thus, after NOS inhibition, vasoconstrictor responses to ET were no longer enhanced in old monkeys. Conclusions —Peripheral vasoconstriction (PE and Ang II) is reduced in old monkeys, as expected. Paradoxically, vasoconstriction induced by ET-1 was actually enhanced in old monkeys, which appears to be a result of impaired endothelium-dependent vasodilation, which with ET-1 should involve the ET B receptor.
Randomized Phase II Study of Gemcitabine Administered at a Fixed Dose Rate or in Combination With Cisplatin, Docetaxel, or Irinotecan in Patients With Metastatic Pancreatic Cancer: CALGB 89904
Authors: Matthew H. Kulke, Margaret A. Tempero, Donna Niedzwiecki, Donna R. Hollis, Hedy L. Kindler, Michael Cusnir, Peter C. Enzinger, Stefan M. Gorsch, Richard M. Goldberg, Robert J. Mayer
Journal: Journal of Clinical Oncology (2009)

Purpose The relative value of gemcitabine-based combination chemotherapy therapy and prolonged infusions of gemcitabine in patients with advanced pancreatic cancer remains controversial. We explored the efficacy and toxicity of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in a multi-institutional, randomized, phase II study. Patients and Methods Patients with metastatic pancreatic cancer were randomly assigned to one of the following four regimens: gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 with cisplatin 50 mg/m 2 on days 1 and 15 (arm A); gemcitabine 1,500 mg/m 2 at a rate of 10 mg/m 2 /min on days 1, 8, and 15 (arm B); gemcitabine 1,000 mg/m 2 with docetaxel 40 mg/m 2 on days 1 and 8 (arm C); or gemcitabine 1,000 mg/m 2 with irinotecan 100 mg/m 2 on days 1 and 8 (arm D). Patients were observed for response, toxicity, and survival. Results Two hundred fifty-nine patients were enrolled onto the study, of whom 245 were eligible and received treatment. Anticipated rates of myelosuppression, fatigue, and expected regimen-specific toxicities were observed. The overall tumor response rates were 12% to 14%, and the median overall survival times were 6.4 to 7.1 months among the four regimens. Conclusion Gemcitabine/cisplatin, fixed dose rate gemcitabine, gemcitabine/docetaxel, and gemcitabine/irinotecan have similar antitumor activity in metastatic pancreatic cancer. In light of recent negative randomized studies directly comparing several of these regimens with standard gemcitabine, none of these approaches can be recommended for routine use in patients with this disease.
MULTIPLE CARCINOMA OF THE SKIN: "PRECANCEROUS DERMATOSIS OF BOWEN."
Authors: J.H. SEQUEIRA, HUBERT TURBULL
Journal: British Journal of Dermatology (1921)

Journal Article MULTIPLE CARCINOMA OF THE SKIN: “PRECANCEROUS DERMATOSIS OF BOWEN.” Get access J.H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S., J.H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S. Physician to the Skin‐Department, and Lecturer on Dermatology, London Hospital Search for other works by this author on: Oxford Academic Google Scholar HUBERT TURBULL, D.M. HUBERT TURBULL, D.M. Professor of Pathology, London Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 33, Issue 5, 1 May 1921, Pages 173–181, https://doi.org/10.1111/j.1365-2133.1921.tb09032.x Published: 01 May 1921
Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin.
Authors: W C Darbonne, G C Rice, M A Mohler, T Apple, C A Hébert, A J Valente, J B Baker
Journal: Journal of Clinical Investigation (1991)

IL-8 (also known as neutrophil-activating peptide 1) is recognized as a potent effector of neutrophil functions. Several different cell types that contact blood, namely T lymphocytes, monocytes, and endothelial cells, secrete this polypeptide following stimulation by cytokines, or lipopolysaccharide. Here we show that when IL-8 is added to blood it rapidly partitions from the plasma fluid to the blood cells and that erythrocytes account for the vast majority of this binding. Analysis of 125I-IL-8 binding [( ala-IL-8]77 form) to human red cells indicates a single, 5 nM Kd affinity class of binding sites, present at approximately 2,000 per red cell representing approximately 15 nmol of red cell IL-8 binding sites per liter of blood. These sites are protease sensitive. Their binding of IL-8 is rapidly reversible and does not result in receptor internalization, although bound IL-8 is resistant to extraction by pH 3 buffer at 5 degrees C. 125I-IL-8 binding to red cells was not inhibited by epidermal growth factor or interleukin 1, but was inhibited by monocyte chemotactic peptide-1, which is not a neutrophil chemotaxin, but is a member of the same family of polypeptides as IL-8. FACS analysis of IL-8-mediated mobilization of Ca2+ in neutrophils indicates that the IL-8 bound to red cells is incapable of stimulating neutrophils. Thus, red cell absorption of IL-8 may function to limit stimulation of leukocytes by IL-8 released into blood.
Essential Role of Lymph Nodes in Contact Hypersensitivity Revealed in Lymphotoxin-α–Deficient Mice
Authors: Paul D. Rennert, Paula S. Hochman, Richard A. Flavell, David D. Chaplin, Sundararajan Jayaraman, Jeffrey L. Browning, Yang-Xin Fu
Journal: The Journal of Experimental Medicine (2001)

Lymph nodes (LNs) are important sentinal organs, populated by circulating lymphocytes and antigen-bearing cells exiting the tissue beds. Although cellular and humoral immune responses are induced in LNs by antigenic challenge, it is not known if LNs are essential for acquired immunity. We examined immune responses in mice that lack LNs due to genetic deletion of lymphotoxin ligands or in utero blockade of membrane lymphotoxin. We report that LNs are absolutely required for generating contact hypersensitivity, a T cell–dependent cellular immune response induced by epicutaneous hapten. We show that the homing of epidermal Langerhans cells in response to hapten application is specifically directed to LNs, providing a cellular basis for this unique LN function. In contrast, the spleen cannot mediate contact hypersensitivity because antigen-bearing epidermal Langerhans cells do not access splenic white pulp. Finally, we formally demonstrate that LNs provide a unique environment essential for generating this acquired immune response by reversing the LN defect in lymphotoxin-α−/− mice, thereby restoring the capacity for contact hypersensitivity.
The ABCs of the anterior cruciate ligament: a primer for magnetic resonance imaging assessment of the normal, injured and surgically repaired anterior cruciate ligament
Authors: J Bining, G Andrews, B B Forster
Journal: British Journal of Sports Medicine (2009)

This article reviews the magnetic resonance imaging (MRI) findings of the native and reconstructed anterior cruciate ligament (ACL). MRI is the most accurate non-invasive modality to evaluate the ACL. Tears of the ACL manifest with direct and indirect signs. The reconstructed ACL has several complications including re-tear and anterior arthrofibrosis, which are also accurately assessed using MRI.
Neurobiological mechanisms of puberty in higher primates
Authors: Tony M Plant, Mandi L Barker-Gibb
Journal: Human Reproduction Update (2004)

Puberty in humans is comprised of two developmental processes; namely, gonadarche and adrenarche. Of the two, gonadarche is fundamentally the most important, and this review examines the neurobiological mechanisms that first prevent, and later trigger, progression into this critically important phase of human development when the ability to first reproduce is established. The review draws extensively upon results obtained by studies of the rhesus monkey (Macaca mulatta), a representative higher primate which, like man, exhibits a postnatal pattern in activity of the hypothalamic–pituitary–gonadal axis that is characterized by a prolonged period of relative quiescence from late infancy until the initiation of the pubertal process. The proximate cause of the prepubertal quiescence in this neuroendocrine axis is the arrest or restraint of the pulsatile mode of hypothalamic GnRH release by a neurobiological brake that holds in check release of this decapeptide, without seeming to down‐regulate the transcriptional activity of the gene encoding GnRH (GnRH‐I). Thus, if neurogenomes control the onset of gonadarche, they must reside upstream from that of the GnRH neuron. The genetic and physiological factors (with a particular emphasis on leptin) that time the application and duration of the prepubertal brake on GnRH release are also considered.
An audit of the management of cutaneous squamous cell carcinoma according to the multiprofessional guidelines
Authors: R.J. Batchelor, G.I. Stables
Journal: British Journal of Dermatology (2006)

Journal Article An audit of the management of cutaneous squamous cell carcinoma according to the multiprofessional guidelines Get access R.J. Batchelor, R.J. Batchelor Leeds Centre for Dermatology, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK E‐mail: rjbatchelor@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar G.I. Stables G.I. Stables Leeds Centre for Dermatology, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK E‐mail: rjbatchelor@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 6, 1 June 2006, Pages 1202–1203, https://doi.org/10.1111/j.1365-2133.2006.07242.x Published: 01 June 2006
Limited expression of R5-tropic HIV-1 in CCR5-positive type 1–polarized T cells explained by their ability to produce RANTES, MIP-1α, and MIP-1β
Authors: Francesco Annunziato, Grazia Galli, Filomena Nappi, Lorenzo Cosmi, Roberto Manetti, Enrico Maggi, Barbara Ensoli, Sergio Romagnani
Journal: Blood (2000)
Lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene transfer in murine lung
Authors: Maria Fe Medina, Gary P Kobinger, John Rux, Mehdi Gasmi, David J Looney, Paul Bates, James M Wilson
Journal: Molecular Therapy (2003)

A human immunodeficiency virus (HIV)-based vector pseudotyped with the Ebola Zaire (EboZ) viral envelope glycoprotein (GP) was recently shown to transduce murine airway epithelia cells in vivo. In this study, the vector was further redesigned to improve gene transfer and also to increase safety. We used mutant EboZ envelopes for pseudotyping, which resulted in higher titers and increased transduction of airway cells in vivo compared to vectors pseudotyped with wild-type EboZ GP. As these envelopes lack regions associated with toxicity of the wild-type EboZ GP, they should also be safer to use for pseudotyping of lentiviral vectors. In addition, lentiviral vectors were created based on feline immunodeficiency virus and shown to have similar efficiency of transduction compared to HIV-based vectors. The creation of lentiviral vectors with highly engineered EboZ envelopes improved the performance of the system and should also increase its safety since only minimal regions of the EboZ envelope, which lack the toxic domain, are used.
A Novel Splice Variant of <i>GLI1</i> That Promotes Glioblastoma Cell Migration and Invasion
Authors: Hui-Wen Lo, Hu Zhu, Xinyu Cao, Amy Aldrich, Francis Ali-Osman
Journal: Cancer Research (2009)

The family of GLI zinc finger transcription factors regulates the expression of genes involved in many important cellular processes, notably embryonal development and cellular differentiation. The glioma-associated oncogene homologue 1 (GLI1) isoform, in particular, has attracted much attention because of its frequent activation in many human cancers and its interactions with other signaling pathways, such as those mediated by K-RAS, transforming growth factor-beta, epidermal growth factor receptor, and protein kinase A. Here, we report the identification of a novel truncated GLI1 splice variant, tGLI1, with an in-frame deletion of 123 bases (41 codons) spanning the entire exon 3 and part of exon 4 of the GLI1 gene. Expression of tGLI1 is undetectable in normal cells but is high in glioblastoma multiforme (GBM) and other cancer cells. Although tGLI1 undergoes nuclear translocalization and transactivates GLI1-binding sites similar to GLI1, unlike GLI1, it is associated with increased motility and invasiveness of GBM cells. Using microarray analysis, we showed >100 genes to be differentially expressed in tGLI1-expressing compared with GLI1-expressing GBM cells, although both cell types expressed equal levels of known GLI1-regulated genes, such as PTCH1. We further showed one of the tGLI1 up-regulated genes, CD24, an invasion-associated gene, to be required for the migratory and invasive phenotype of GBM cells. These data provide conclusive evidence for a novel gain-of-function GLI1 splice variant that promotes migration and invasiveness of GBM cells and open up a new research paradigm on the role of the GLI1 pathway in malignancy.
Inflammatory Response and Body Composition in Chronic Obstructive Pulmonary Disease
Authors: ABDULLAH A. EID, ALINA A. IONESCU, LISETTE S. NIXON, VANESSA LEWIS-JENKINS, STEPHANIE B. MATTHEWS, TIMOTHY L. GRIFFITHS, DENNIS J. SHALE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Weight loss in chronic obstructive airways disease (COPD) is associated with an increased energy cost of breathing. To determine an association between body composition and the inflammatory response we studied 80 clinically stable patients. Body composition was determined anthropometrically and skeletal muscle mass was determined as the creatinine–height index (CHI). Forty patients had their nitrogen balance determined. Circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor α (TNF- α ), and their soluble receptors were determined for 68 patients. Body mass index (BMI) was normal ( > 20 kg/m2) in 55 patients, of whom 17 (31%) had a low CHI ( < 80% predicted). A reduced CHI was associated with increased circulating levels of IL-6 (p = 0.001), TNF- α (p = 0.032) and their soluble receptors IL-6sr (p = 0.002), TNF- α sr1 (p = 0.03), and TNF- α sr2 (p = 0.001). Patients with a normal BMI and low CHI had inflammatory mediator levels similar to patients with a low BMI and CHI; both were significantly greater than in those with a normal BMI and CHI. Nitrogen balance was similar between normal and low CHI groups, although nitrogen excretion was significantly increased in the low CHI group. Skeletal muscle loss in COPD is probably multifactorial in origin, but our data suggest a link with systemic inflammation, even when weight loss is inapparent.
Inhibition of Protein Phosphatase 2A Radiosensitizes Pancreatic Cancers by Modulating CDC25C/CDK1 and Homologous Recombination Repair
Authors: Dongping Wei, Leslie A. Parsels, David Karnak, Mary A. Davis, Joshua D. Parsels, Amanda C. Marsh, Lili Zhao, Jonathan Maybaum, Theodore S. Lawrence, Yi Sun, Meredith A. Morgan
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer and thus improve survival, we conducted an siRNA library screen in pancreatic cancer cells. We investigated PPP2R1A, a scaffolding subunit of protein phosphatase 2A (PP2A) as a lead radiosensitizing target. Experimental Design: We determined the effect of PP2A inhibition by genetic (PPP2R1A siRNA) and pharmacologic (LB100, a small molecule entering phase I clinical trials) approaches on radiosensitization of Panc-1 and MiaPaCa-2 pancreatic cancer cells both in vitro and in vivo. Results: PPP2R1A depletion by siRNA radiosensitized Panc-1 and MiaPaCa-2 cells, with radiation enhancement ratios of 1.4 (P &amp;lt; 0.05). Likewise, LB100 produced similar radiosensitization in pancreatic cancer cells, but minimal radiosensitization in normal small intestinal cells. Mechanistically, PPP2R1A siRNA or LB100 caused aberrant CDK1 activation, likely resulting from accumulation of the active forms of PLK1 (pPLK1 T210) and CDC25C (pCDC25C T130). Furthermore, LB100 inhibited radiation-induced Rad51 focus formation and homologous recombination repair (HRR), ultimately leading to persistent radiation-induced DNA damage, as reflected by γ-H2AX expression. Finally, we identified CDC25C as a key PP2A substrate involved in LB100-mediated radiosensitization as depletion of CDC25C partially reversed LB100-mediated radiosensitization. In a mouse xenograft model of human pancreatic cancer, LB100 produced significant radiosensitization with minimal weight loss. Conclusions: Collectively, our data show that PP2A inhibition radiosensitizes pancreatic cancer both in vitro and in vivo via activation of CDC25C/CDK1 and inhibition of HRR, and provide proof-of-concept evidence that PP2A is a promising target for the improvement of local therapy in pancreatic cancer. Clin Cancer Res; 19(16); 4422–32. ©2013 AACR.