tbuckley/cabot-search huggingface dataset:
Effects of Long-Term Nitroglycerin Treatment on Endothelial Nitric Oxide Synthase (NOS III) Gene Expression, NOS III–Mediated Superoxide Production, and Vascular NO Bioavailability
Authors: Thomas Münzel, Huige Li, Hanke Mollnau, Ulrich Hink, Edi Matheis, Mark Hartmann, Mathias Oelze, Mikhail Skatchkov, Ascan Warnholtz, Linda Duncker, Thomas Meinertz, Ulrich Förstermann
Journal: Circulation Research (2000)

Abstract —Long-term nitroglycerin (NTG) treatment has been shown to be associated with cross-tolerance to endothelium-dependent vasodilators. It may involve increased production of reactive oxygen species (such as superoxide, O 2 ·− ) that rapidly inactivate the nitric oxide (NO) released from the endothelial cells. It remains to be elucidated, however, whether long-term treatment with NTG alters the activity and expression of the endothelial NO synthase (NOS III) and whether this enzyme can contribute to O 2 ·− formation. We studied the influence of long-term NTG treatment on the expression of NOS III as assessed by RNase protection assay and Western blot. Tolerance was measured ex vivo in organ chamber experiments with rat aortic rings. O 2 ·− and NO formation were quantified using lucigenin- and Cypridina luciferin analog–enhanced chemiluminescence as well as electron spin resonance (ESR) spectroscopy. Treatment of Wistar rats with NTG (Alzet osmotic minipumps, NTG concentration 10 μg · kg −1 · min −1 ) for 3 days caused marked tolerance, cross-tolerance to the endothelium-dependent vasodilator acetylcholine, and a significant increase in O 2 ·− -induced chemiluminescence. Tolerance was associated with a significant increase in NOS III mRNA to 236±28% and NOS III protein to 239±17%. In control vessels, the NOS inhibitor N G -nitro- l -arginine (L-NNA) increased the O 2 ·− -mediated chemiluminescence, indicating that basal production of endothelium-derived NO depresses the baseline chemiluminescence signal. In the setting of tolerance, however, L-NNA decreased steady-state O 2 ·− levels, indicating the involvement of NOS III in O 2 ·− formation. Likewise, A23187-induced, NOS III–mediated O 2 ·− production was more pronounced in tolerant than in control vessels. Vascular NO bioavailability as assessed with ESR spectroscopy using iron-thiocarbamate as a trap for NO was significantly reduced in tolerant vessels. Pretreatment of tolerant tissue in vitro with the protein kinase C (PKC) inhibitors reduced basal and stimulated NOS III–mediated O 2 ·− production and partially reversed vascular tolerance. These findings suggest that NTG treatment increases the expression of a dysfunctional NOS III gene, leading to increased formation of O 2 ·− and decreased vascular NO bioavailability. Normalization of NOS III–mediated O 2 ·− production and improvement of tolerance with PKC inhibition suggests an important role for PKC isoforms in mediating vascular dysfunction caused by long-term NTG treatment. The full text of this article is available at http://www.circresaha.org.
Lifetime risk of oesophageal adenocarcinoma in patients with Barrett's columnar-lined oesophagus registered with UK national Barrett's oesophagus registry
Authors: P. Gatenby, C. P. Caygill, C. Wall, S. Bhatacharjee, J. R. Ramus, A. Watson, M. C. Winslet
Journal: Gut (2011)

<h3>Introduction</h3> The annual rate of development of high-grade dysplasia or adenocarcinoma in Barrett9s columnar-lined oesophagus is 1.0%.12 This study uses data from the UK National Barrett9s Oesophagus Registry (UKBOR) and the Office of National Statistics to predict the average number of surveillance endoscopies and lifetime risk of development of high-grade dysplasia and adenocarcinoma. <h3>Methods</h3> Data on patient gender, age at columnar-lined oesophagus diagnosis and date of columnar-lined oesophagus diagnosis were collected for patients diagnosed between 1994 and 2008 from centres registering ≤20 patients with UKBOR. Patients were included if aged between 18 and 95 years at date of diagnosis. This yielded a total of 7877 patients from 36 centres in the UK. Life expectancy/years at risk was evaluated using age at diagnosis and predicted life years from life expectancy tables.3 Standard surveillance practice was modelled as a single endoscopy at diagnosis with 3 yearly surveillance for no dysplasia and 6 monthly follow-up endoscopy for low-grade dysplasia or indefinite changes for dysplasia (14.7% of diagnostic endoscopy findings and 19.6% of subsequent endoscopy findings). <h3>Results</h3> There were 5137 males, mean age 61.6 years at diagnosis and 2740 females, mean age 67.3 years at diagnosis. The mean predicted years of life (exposure time to the risk of developing malignancy in the metaplastic segment) were 23.1 and 20.7 years, respectively, and 22.2 years overall. This would predict that the lifetime risk of developing high-grade dysplasia or cancer would be between 1:4 and 1:5 and of adenocarcinoma would be between 1:7 and 1:8. The average number of surveillance OGDs during a patient9s lifetime using the above surveillance protocol is 9.8 per patient. <h3>Conclusion</h3> These data predict a significant lifetime risk of development of high-grade dysplasia or adenocarcinoma in patients diagnosed with Barrett9s oesophagus. The total burden of surveillance endoscopies excluding those for therapeutic interventions to the metaplastic segment or for follow-up of high-grade dysplasia, cancer or endoluminal treatment is 9.8 per patient.
Microbial contamination of single- and multiple-dose vials after opening in a pulmonary teaching hospital
Authors: Shadi Baniasadi, Atosa Dorudinia, Mandana Mobarhan, Fanak Fahimi
Journal: European Respiratory Journal (2012)

Introduction: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections.  Aims: We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials (SDVs and MDVs) in the largest pulmonary teaching hospital in Iran.  Methods: In a period of 2 month, opened SDVs and MDVs from different wards were collected by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media.  Results: Microbial contamination was identified in 11 of 205 (5%) of vials. The highest contamination rate was 14.29% for vials used in interventional bronchoscopy unit. The most frequent contaminated medications were Insulin and potassium chloride. Gram-positive bacteria (81.82%) were more significantly involved than gram-negative ones (9.09%) and fungi (9.09%), with the highest frequency for Staphylococcus epidermidis.  Conclusions: Use of safe injection practice is critical to prevent microbial contamination of products administered to patients. A training program for health care workers in aseptic techniques and written guidelines for aseptic handling of intravenous solutions are required.
Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction
Authors: Geoffrey de Couto, Weixin Liu, Eleni Tseliou, Baiming Sun, Nupur Makkar, Hideaki Kanazawa, Moshe Arditi, Eduardo Marbán
Journal: Journal of Clinical Investigation (2015)

Ischemic injury in the heart induces an inflammatory cascade that both repairs damage and exacerbates scar tissue formation. Cardiosphere-derived cells (CDCs) are a stem-like population that is derived ex vivo from cardiac biopsies; they confer both cardioprotection and regeneration in acute myocardial infarction (MI). While the regenerative effects of CDCs in chronic settings have been studied extensively, little is known about how CDCs confer the cardioprotective process known as cellular postconditioning. Here, we used an in vivo rat model of ischemia/reperfusion (IR) injury–induced MI and in vitro coculture assays to investigate how CDCs protect stressed cardiomyocytes. Compared with control animals, animals that received CDCs 20 minutes after IR had reduced infarct size when measured at 48 hours. CDCs modified the myocardial leukocyte population after ischemic injury. Specifically, introduction of CDCs reduced the number of CD68+ macrophages, and these CDCs secreted factors that polarized macrophages toward a distinctive cardioprotective phenotype that was not M1 or M2. Systemic depletion of macrophages with clodronate abolished CDC-mediated cardioprotection. Using both in vitro coculture assays and a rat model of adoptive transfer after IR, we determined that CDC-conditioned macrophages attenuated cardiomyocyte apoptosis and reduced infarct size, thereby recapitulating the beneficial effects of CDC therapy. Together, our data indicate that CDCs limit acute injury by polarizing an effector macrophage population within the heart.
Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies
Authors: M. Etminan
Journal: BMJ (2003)

To quantify the risk of Alzheimer's disease in users of all non-steroidal anti-inflammatory drugs (NSAIDs) and users of aspirin and to determine any influence of duration of use.Systematic review and meta-analysis of observational studies published between 1966 and October 2002 that examined the role of NSAID use in preventing Alzheimer's disease. Studies identified through Medline, Embase, International Pharmaceutical Abstracts, and the Cochrane Library.Nine studies looked at all NSAIDs in adults aged > 55 years. Six were cohort studies (total of 13 211 participants), and three were case-control studies (1443 participants). The pooled relative risk of Alzheimer's disease among users of NSAIDs was 0.72 (95% confidence interval 0.56 to 0.94). The risk was 0.95 (0.70 to 1.29) among short term users (< 1 month) and 0.83 (0.65 to 1.06) and 0.27 (0.13 to 0.58) among intermediate term (mostly < 24 months) and long term (mostly > 24 months) users, respectively. The pooled relative risk in the eight studies of aspirin users was 0.87 (0.70 to 1.07).NSAIDs offer some protection against the development of Alzheimer's disease. The appropriate dosage and duration of drug use and the ratios of risk to benefit are still unclear.
The vagal innervation of the gut and immune homeostasis
Authors: Gianluca Matteoli, Guy E Boeckxstaens
Journal: Gut (2012)

The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.
The Major Histocompatibility Complex–related Fc Receptor for IgG (FcRn) Binds Albumin and Prolongs Its Lifespan
Authors: Chaity Chaudhury, Samina Mehnaz, John M. Robinson, William L. Hayton, Dennis K. Pearl, Derry C. Roopenian, Clark L. Anderson
Journal: The Journal of Experimental Medicine (2003)

The inverse relationship between serum albumin concentration and its half-life suggested to early workers that albumin would be protected from a catabolic fate by a receptor-mediated mechanism much like that proposed for IgG. We show here that albumin binds FcRn in a pH dependent fashion, that the lifespan of albumin is shortened in FcRn-deficient mice, and that the plasma albumin concentration of FcRn-deficient mice is less than half that of wild-type mice. These results affirm the hypothesis that the major histocompatibility complex–related Fc receptor protects albumin from degradation just as it does IgG, prolonging the half-lives of both.
<i>MET</i> Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib
Authors: Jochen K. Lennerz, Eunice L. Kwak, Allison Ackerman, Michael Michael, Stephen B. Fox, Kristin Bergethon, Gregory Y. Lauwers, James G. Christensen, Keith D. Wilner, Daniel A. Haber, Ravi Salgia, Yung-Jue Bang, Jeffrey W. Clark, Benjamin J. Solomon, A. John Iafrate
Journal: Journal of Clinical Oncology (2011)

Amplification of the MET proto-oncogene in gastroesophageal cancer (GEC) may constitute a molecular marker for targeted therapy. We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an expanded phase I cohort study.
Antihypertensive Effects of Drospirenone With 17β-Estradiol, a Novel Hormone Treatment in Postmenopausal Women With Stage 1 Hypertension
Authors: William B. White, Bertram Pitt, Richard A. Preston, Vladimir Hanes
Journal: Circulation (2005)

Background— Drospirenone (DRSP) is a novel progestin with antimineralocorticoid activity that has been developed for hormone therapy in combination with 17β-estradiol (E2) in postmenopausal women. In prior studies with DRSP in postmenopausal women that were focused on relief of menopausal symptoms, DRSP/E2 yielded significant reductions in blood pressure (BP). Methods and Results— The effects of 3 mg DRSP/1 mg E2 on clinic and 24-hour ambulatory BP as well as potassium homeostasis were evaluated in postmenopausal women with stage 1 hypertension (systolic, 140 to 159 and/or diastolic, 90 to 99 mm Hg) in a 12-week, multicenter, double-blind, randomized, placebo-controlled study. Clinic BPs were measured at baseline and at 2, 4, 6, 8, and 12 weeks of therapy, whereas potassium was measured at 2, 6, and 12 weeks of therapy. Ambulatory BP was performed in a substudy at baseline and at the end of the trial. In the intention-to-treat population of 213 women, the clinic BP was reduced significantly on DRSP/E2 (clinic BP, −14.1/−7.9 for DRSP/E2 versus −7.1/−4.3 mm Hg for placebo, P &lt;0.0001). In the subgroup of 43 women with ambulatory BP monitoring, the 24-hour BP fell by −8.5/−4.2 mm Hg versus −1.8/−1.6 mm Hg on placebo ( P =0.002/0.07). There were no significant changes from baseline in potassium levels or in the incidence of hyperkalemia (≥5.5 meq/L) on DRSP/E2 compared with placebo. Conclusions— Combination therapy with DRSP/E2 significantly lowered both clinic and 24-hour systolic BP in postmenopausal women with stage 1 systolic hypertension. This characteristic may lead to benefit for cardiovascular risk reduction in this population.
Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil
Authors: M. Nucci, M. Garnica, A.B. Gloria, D.S. Lehugeur, V.C.H. Dias, L.C. Palma, P. Cappellano, K.Y. Fertrin, F. Carlesse, B. Simões, M.D. Bergamasco, C.A. Cunha, A. Seber, M.P.D. Ribeiro, F. Queiroz-Telles, M.L.M. Lee, M.L. Chauffaille, L. Silla, C. A. de Souza, A.L. Colombo
Journal: Clinical Microbiology and Infection (2012)

Invasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil.
Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens.
Authors: E Baixeras, B Huard, C Miossec, S Jitsukawa, M Martin, T Hercend, C Auffray, F Triebel, D Piatier-Tonneau
Journal: The Journal of Experimental Medicine (1992)

The lymphocyte activation gene 3 (LAG-3), expressed in human activated T and natural killer (NK) cells, is closely related to CD4 at the gene and protein levels. We report here the initial characterization of the LAG-3-encoded protein. We have generated two monoclonal antibodies after immunization of mice with a 30-amino acid peptide that corresponds to an exposed extra loop region present in the LAG-3 immunoglobulin-like first domain. The reactivity of these reagents is directed against LAG-3 since they recognize both membrane-expressed and soluble recombinant LAG-3 molecules produced in a baculovirus expression system. The two antibodies are likely to react with the same or closely related epitope (termed LAG-3.1) exposed on the LAG-3 first domain extra loop, as assessed in competition experiments on LAG-3-expressing activated lymphocytes. Cellular distribution analysis indicated that the LAG-3.1 epitope is expressed on activated T (both CD4+ and CD8+ subsets) and NK cells, and not on activated B cells or monocytes. In immunoprecipitation experiments performed on activated T and NK cell lysates, a 70-kD protein was detected after SDS-PAGE analysis. 45-kD protein species were also immunoprecipitated. Both the 70- and 45-kD proteins were shown to be N-glycosylated. In Western blot analysis, only the former molecule was recognized by the anti-LAG-3 antibodies, demonstrating that it is LAG-3 encoded. These anti-LAG-3 antibodies were used to investigate whether the LAG-3 protein interacts with the CD4 ligands. By using a high-level expression cellular system based on COS-7 cell transfection with recombinant CDM8 vectors and a quantitative cellular adhesion assay, we demonstrate that rosette formation between LAG-3-transfected COS-7 cells and human leukocyte antigen (HLA) class II-bearing B lymphocytes is specifically dependent on LAG-3/HLA class II interaction. In contrast to CD4, LAG-3 does not bind the human immunodeficiency virus gp120. This initial characterization will guide further studies on the functions of this molecule, which may play an important role in immune responses mediated by T and NK lymphocytes.
Effects of corticosteroids on urinary ammonium excretion in humans.
Authors: M M Waybill, J N Clore, R A Emerick, C O Watlington, A C Schoolwerth
Journal: Journal of the American Society of Nephrology (1994)

This study was designed to examine the selective effects of glucocorticoid and mineralocorticoid classes of steroid hormones on urinary ammonium excretion in humans. In 22 10-day studies, normal male volunteers received either 9 alpha-fludrohydrocortisone or hydrocortisone, alone or with the receptor antagonist spironolactone or mifepristone. The small but significant increase in ammonium excretion noted with the administration of 9 alpha-fludrohydrocortisone was associated with a significant decrease in serum potassium. In contrast, a significantly larger increase in ammonium excretion was noted with hydrocortisone, without concomitant electrolyte changes. Spironolactone did not alter the effect on ammonium excretion by either corticosteroid, whereas mifepristone markedly blunted the hydrocortisone-induced increase in urinary ammonium excretion. It was concluded that glucocorticoids increase urinary ammonium excretion in humans and that this effect occurs through binding to the Type II (glucocorticoid) receptor rather than by cross-occupancy of the Type I (mineralocorticoid) receptor.
Fanconi's anemia and malignancies
Authors: Blanche P. Alter
Journal: American Journal of Hematology (1996)

Patients with Fanconi's anemia (FA) are at a high risk for development of malignancies. It is well-known that leukemia occurs in ∼10% of cases, with increasing risk with age. Less commonly recognized is the risk for myelodysplastic syndromes (∼5%); the relationship between myelodysplasia and evolution to leukemia remains speculative. What also needs to be emphasized is that older patients have an ever-increasing risk for development of solid tumors, with at least 5% reported to have liver tumors (male:female ratio, 2:1) and an equal number of other cancers (female:male ratio, 3:1, even after exclusion of gynecologic malignancies). Hematologists have tended to focus on aplastic anemia and leukemia. As FA patients live longer, more of the other malignancies will occur, perhaps related to cord blood or bone marrow transplant, or treatment with cytokines. This review identifies the types of tumors for which patients with Fanconi's anemia are at risk. © 1996 Wiley-Liss, Inc.
What do we need to know about speciation?
Authors: Roger Butlin, Allan Debelle, Claudius Kerth, Rhonda R. Snook, Leo W. Beukeboom, Ruth Castillo Cajas, Wenwen Diao, Martine E. Maan, Silvia Paolucci, Franz J. Weissing, Louis van de Zande, Anneli Hoikkala, Elzemiek Geuverink, Jackson Jennings, Maaria Kankare, K. Emily Knott, Venera I. Tyukmaeva, Christos Zoumadakis, Michael G. Ritchie, Daniel Barker, Elina Immonen, Mark Kirkpatrick, Mohamed Noor, Constantino Macias Garcia, Thomas Schmitt, Menno Schilthuizen
Journal: Trends in Ecology & Evolution (2011)