tbuckley/cabot-search huggingface dataset:
Mechanisms of dyspnoea relief and improved exercise endurance after furosemide inhalation in COPD
Authors: D Jensen, K Amjadi, V Harris-McAllister, K A Webb, D E O'Donnell
Journal: Thorax (2008)

<h3>Background:</h3> This study examined the effects of inhaled furosemide on the ventilatory and perceptual response to high-intensity constant-load cycle exercise in chronic obstructive pulmonary disease (COPD). <h3>Methods:</h3> In a randomised, double-blind, placebo-controlled, crossover study, 20 patients with COPD (mean (SD) forced expiratory volume in 1 s 45 (15)% predicted) received either nebulised furosemide 40 mg or placebo on two separate days. Thirty minutes after each treatment, patients performed pulmonary function tests and a symptom-limited cycle exercise test at 75% of their maximum incremental work rate. Changes in spirometry, plethysmographic lung volumes, dynamic operating lung volumes, ventilation, breathing pattern, cardiovascular function, dyspnoea intensity and exercise endurance time were compared between treatments. <h3>Results:</h3> Compared with placebo, treatment with furosemide resulted in a mean (SD) decrease in dyspnoea intensity at the highest equivalent exercise time (ie, isotime for each patient) of 0.9 (1.0) Borg units (p&lt;0.01) and an increase in exercise endurance time of 1.65 (0.63) min (p&lt;0.05). These improvements were associated with increases in dynamic inspiratory capacity, tidal volume and mean tidal expiratory flow rates at isotime (p&lt;0.01). The eight patients whose exercise endurance time improved by &gt;1 min had greater changes in operating lung volumes (p&lt;0.05), submaximal oxygen pulse (p&lt;0.05) and oxygen uptake (p = 0.05) than those in whom exercise endurance time did not improve. <h3>Conclusion:</h3> Alleviation of exertional dyspnoea after single-dose furosemide inhalation in COPD is multifactorial but improvements in dynamic ventilatory mechanics are contributory in some individuals.
Interleukin 1beta and tumour necrosis factor alpha secreting cells are increased in the peripheral blood of patients with primary Sjogren's syndrome
Authors: P Willeke
Journal: Annals of the Rheumatic Diseases (2003)

To study systemic alterations of cytokine secreting peripheral blood mononuclear cells (PBMC) in primary Sjögren's syndrome (pSS) and their relation to common clinical and immunological manifestations of this disease.PBMC spontaneously secreting tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and interleukin 6 (IL6) were assessed by enzyme linked immunospot (ELISPOT) analysis in a cohort of 31 patients with pSS fulfilling the modified European classification criteria. Nineteen healthy volunteers served as controls. ELISPOT results were correlated with glandular and extraglandular manifestations and autoantibody titres-that is, rheumatoid factor (RF) isotypes, anti-Ro/SS-A, anti-La/SS-B as determined by an enzyme linked immunosorbent assay (ELISA) technique.The number of TNFalpha and IL1beta secreting cells was significantly higher in patients with pSS than in controls. No differences were detected in the number of IL6 secreting PBMC. Patients with recurrent parotid swelling (RPS) had a significantly increased number of IL1beta secreting PBMC. Moreover, the number of IL1beta secreting PBMC correlated with the disease duration (r(s)=0.479; p<0.01) and with the concentration of IgM RF (r(s)=0.63; p<0.01) and IgG RF (r(s)=0.42; p<0.05). Other autoantibodies did not correlate with cytokine secreting PBMC.The increased systemic secretion of IL1beta and TNFalpha in patients with pSS points to a pathogenic impact of these cytokines in this autoimmune disease. In particular the correlation of IL1beta secreting PBMC with RPS and RF production indicates that IL1beta is a crucial regulator in the development of local and systemic disease manifestations.
Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B*1
Authors: Yosuke Morimitsu, David E. Kleiner, Hari S. Conjeevaram, Chu Chieh Hsia, Adrian M. Di Bisceglie, Edward Tabor
Journal: Hepatology (1995)

The effect of interferon alfa (IFN-α) therapy on the expression of transforming growth factor alpha (TGF-α) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-α for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-α in an avidin-biotin-peroxidase-complex system. The expression of TGF-α in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-α expression before or after therapy between 13 patients receiving daily IFN-α, 13 receiving alternate-day IFN-α, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients (“responders”); the 18 other patients were “nonresponders”. Expression of TGF-α before IFN-α therapy was significantly higher in responders than in nonresponders; after IFN-α therapy, TGF-α expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-α in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-α therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond.
Accelerated Degeneration of a Bovine Pericardial Bioprosthetic Aortic Valve in Children and Young Adults
Authors: Susan F. Saleeb, Jane W. Newburger, Tal Geva, Christopher W. Baird, Kimberlee Gauvreau, Robert F. Padera, Pedro J. del Nido, Michele J. Borisuk, Stephen P. Sanders, John E. Mayer
Journal: Circulation (2014)

Experience with aortic valve replacement (AVR) with current-generation pericardial bioprostheses in young patients is limited. The death of a child with accelerated bioprosthetic aortic stenosis prompted enhanced surveillance of all such patients at our institution.We reviewed records of 27 patients who had undergone AVR (median follow-up, 13.7 months) with a bovine pericardial bioprosthesis at ≤30 years of age. In the Mitroflow LXA valve group (n=15), freedom from valve failure was 100% at 1 year, 53% (95% confidence interval, 12-82) at 2 years, and 18% (95% confidence interval, 1-53) at 3 years. No Magna/Magna Ease valves (n=12) failed by 3 years. Among valve failure patients, median age at AVR was 12 years (range, 10-21 years). Life-threatening prosthetic aortic stenosis was detected at a median of 6 months after prior echocardiograms showing mild or less gradients. Patients with Mitroflow LXA compared with Magna/Magna Ease valves were smaller (median body surface area, 1.42 versus 1.93 m(2); P=0.002) and younger (median age, 13.0 versus 20.9 years; P=0.02) at AVR. Pathology demonstrated diffuse intrinsic leaflet calcification, not associated with inflammation or infection, and virtually immobile leaflets in closed position.Young patients undergoing AVR with Mitroflow LXA pericardial valves are at high risk for rapid progression from mild or less to severe aortic stenosis over months, highlighting their need for heightened echocardiographic surveillance and suggesting that this aortic bioprosthesis should not be implanted in the young. Current data are insufficient to assess the safety of AVR with other pericardial bioprostheses in children and the youngest adults.
Hypoxia-Inducible Factor-2α Transactivates Abcg2 and Promotes Cytoprotection in Cardiac Side Population Cells
Authors: Cindy M. Martin, Anwarul Ferdous, Teresa Gallardo, Caroline Humphries, Hesham Sadek, Arianna Caprioli, Joseph A. Garcia, Luke I. Szweda, Mary G. Garry, Daniel J. Garry
Journal: Circulation Research (2008)

Stem and progenitor cell populations occupy a specialized niche and are consequently exposed to hypoxic as well as oxidative stresses. We have previously established that the multidrug resistance protein Abcg2 is the molecular determinant of the side population (SP) progenitor cell population. We observed that the cardiac SP cells increase in number more than 3-fold within 3 days of injury. Transcriptome analysis of the SP cells isolated from the injured adult murine heart reveals increased expression of cytoprotective transcripts. Overexpression of Abcg2 results in an increased ability to consume hydrogen peroxide and is associated with increased levels of α-glutathione reductase protein expression. Importantly, overexpression of Abcg2 also conferred a cell survival benefit following exposure to hydrogen peroxide. To further examine the molecular regulation of the Abcg2 gene, we demonstrated that hypoxia-inducible factor (HIF)-2α binds an evolutionary conserved HIF-2α response element in the murine Abcg2 promoter. Transcriptional assays reveal a dose-dependent activation of Abcg2 expression by HIF-2α. These results support the hypothesis that Abcg2 is a direct downstream target of HIF-2α which functions with other factors to initiate a cytoprotective program for this progenitor SP cell population that resides in the adult heart.
Postpartum Remodeling, Lactation, and Breast Cancer Risk: Summary of a National Cancer Institute–Sponsored Workshop
Authors: Jessica M. Faupel-Badger, Kathleen F. Arcaro, Jane J. Balkam, A. Heather Eliassen, Foteini Hassiotou, Carlito B. Lebrilla, Karin B. Michels, Julie R. Palmer, Pepper Schedin, Alison M. Stuebe, Christine J. Watson, Mark E. Sherman
Journal: JNCI Journal of the National Cancer Institute (2012)

The pregnancy-lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes.
Estrogen deficiency and bone loss: an inflammatory tale
Authors: M. N. Weitzmann
Journal: Journal of Clinical Investigation (2006)

Estrogen plays a fundamental role in skeletal growth and bone homeostasis in both men and women. Although remarkable progress has been made in our understanding of how estrogen deficiency causes bone loss, the mechanisms involved have proven to be complex and multifaceted. Although estrogen is established to have direct effects on bone cells, recent animal studies have identified additional unexpected regulatory effects of estrogen centered at the level of the adaptive immune response. Furthermore, a potential role for reactive oxygen species has now been identified in both humans and animals. One major challenge is the integration of a multitude of redundant pathways and cytokines, each apparently capable of playing a relevant role, into a comprehensive model of postmenopausal osteoporosis. This Review presents our current understanding of the process of estrogen deficiency-mediated bone destruction and explores some recent findings and hypotheses to explain estrogen action in bone. Due to the inherent difficulties associated with human investigation, many of the lessons learned have been in animal models. Consequently, many of these principles await further validation in humans.
Parental Smoking and Lung Function in Children
Authors: Hanns Moshammer, Gerard Hoek, Heike Luttmann-Gibson, Manfred A. Neuberger, Temenuga Antova, Ulrike Gehring, Frantiska Hruba, Sam Pattenden, Peter Rudnai, Hana Slachtova, Renata Zlotkowska, Tony Fletcher
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Both prenatal and postnatal passive smoking have been linked with respiratory symptoms and asthma in childhood. Their differential contributions to lung function growth in the general children's population are less clear.Objective: To study the relative impact of pre- and postnatal exposure on respiratory functions of primary school children in a wide range of geographic settings, we analyzed flow and volume data of more than 20,000 children (aged 6–12 yr) from nine countries in Europe and North America.Methods: Exposure information had been obtained by comparable questionnaires, and spirometry followed a protocol of the American Thoracic Society/European Respiratory Society. Linear and logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytic tools.Main Results: Smoking during pregnancy was associated with decreases in lung function parameters between −1% (FEV1) and −6% maximal expiratory flow at 25% of vital capacity left (MEF25). A 4% lower maximal midexpiratory flow (MMEF) corresponded to a 40% increase in the risk of poor lung function (MMEF < 75% of expected). Associations with current passive smoking were weaker though still measurable, with effects ranging from −0.5% (FEV1) to −2% maximal expiratory flow (MEF50).Conclusions: Considering the high number of children exposed to maternal smoking in utero and the even higher number exposed to passive smoking after birth, this risk factor for reduced lung function growth remains a serious pediatric and public health issue.
INDIRECT VISUALIZATION OF STAPHYLOCOCCUS AUREUS PROTEIN A
Authors: D. Scott Nickerson, James G. White, Göran Kronvall, Ralph C. Williams, Paul G. Quie
Journal: The Journal of Experimental Medicine (1970)

Specific but nonimmunologic reaction between staphylococcal protein A and the Fc portion of gamma globulin provided the basis for ultrastructural studies to determine the localization of protein A, using intact staphylococci and labeled myeloma gamma G-globulin. Protein A appeared to be part of the outermost layer of the staphylococcal cell wall. Strains with protein A demonstrated a coating of myeloma globulin over the entire bacterial surface. There was no coating of strains without protein A. Identification of protein A on the surface of the staphylococcal cell wall provides evidence that this may be the first material in contact with host environment. It probably accounts for apparent cross-reactions of staphylococci with antibodies to many antigens. More importantly, even in the nonimmune host protein A immunoglobulin reactivity may initiate complement activation and inflammatory reactions including chemotaxis and pus formation.
Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial
Authors: Sandro Pignata, Giovanni Scambia, Dionyssios Katsaros, Ciro Gallo, Eric Pujade-Lauraine, Sabino De Placido, Alessandra Bologna, Beatrice Weber, Francesco Raspagliesi, Pierluigi Benedetti Panici, Gennaro Cormio, Roberto Sorio, Maria Giovanna Cavazzini, Gabriella Ferrandina, Enrico Breda, Viviana Murgia, Cosimo Sacco, Saverio Cinieri, Vanda Salutari, Caterina Ricci, Carmela Pisano, Stefano Greggi, Rossella Lauria, Domenica Lorusso, Claudia Marchetti, Luigi Selvaggi, Simona Signoriello, Maria Carmela Piccirillo, Massimo Di Maio, Francesco Perrone
Journal: The Lancet Oncology (2014)
Enhancing effect of the endocrine disruptor para-nonylphenol on the generation of reactive oxygen species in human blood neutrophils.
Authors: Yasuji Okai, Eisuke F Sato, Kiyoka Higashi-Okai, Masayasu Inoue
Journal: Environmental Health Perspectives (2004)

Although para-nonylphenol (NP) is known as an endocrine disruptor, the immunologic effect of NP has been poorly analyzed. We found that NP from 5 to 50 microM caused a dose-dependent stimulatory effect on the generation of reactive oxygen species (ROS) in human blood neutrophils, which was measured by using a chemiluminescence reagent, luminol. Furthermore, ROS-scavenging enzymes such as catalase and superoxide dismutase and antioxidative agents alpha-tocopherol and beta-carotene showed strong preventive effects on NP-induced ROS generation. To analyze the biochemical mechanism of NP-induced ROS generation in human neutrophils, we investigated the effects of different types of metabolic inhibitor for the activation pathways of ROS generation in the cells. Reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase inhibitor, diphenyl iodonium chloride and the myeloperoxidase inhibitor sodium azide (NaN3) showed remarkable inhibitory effects on ROS generation induced by NP, but an inhibitor against mitochondrial respiratory function, potassium cyanide (KCN), did not exhibit significant effect. Furthermore, the phosphatidylinositol-3 (PI3) kinase inhibitor wortmannin and the tyrosine kinase inhibitor protein phosphorylation inhibitor 1 (PP1) caused strong suppression against NP-induced ROS generation. The selective protein kinase C inhibitor Ro-32-0432, p38 MAP kinase inhibitor SB 203580, and ERK MAP kinase inhibitor PD 98059 also showed significant suppressive effects on NP-induced ROS generation. These results suggest that NP causes an enhancing effect on ROS generation in human blood neutrophils through the activation of signal transduction pathways associated with the respiratory burst function in these cells. Additionally, to examine in vivo effects of NP, we also analyzed the effects of NP itself and the synergistic effects of NP and a typical inflammatory agent, opsonized zymosan, on human whole blood including neutrophils.
Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts
Authors: Wolfram-Hubertus Zimmermann, Ivan Melnychenko, Gerald Wasmeier, Michael Didié, Hiroshi Naito, Uwe Nixdorff, Andreas Hess, Lubos Budinsky, Kay Brune, Bjela Michaelis, Stefan Dhein, Alexander Schwoerer, Heimo Ehmke, Thomas Eschenhagen
Journal: Nature Medicine (2006)
Differential Clinical Responses to Everolimus-Eluting and Paclitaxel-Eluting Coronary Stents in Patients With and Without Diabetes Mellitus
Authors: Gregg. W. Stone, Elvin Kedhi, Dean J. Kereiakes, Helen Parise, Martin Fahy, Patrick W. Serruys, Pieter C. Smits
Journal: Circulation (2011)

Some (but not all) prior trials have reported differential outcomes after percutaneous coronary intervention with paclitaxel-eluting stents versus stents eluting rapamycin analogs according to the presence of diabetes mellitus. These studies lacked sufficient power to examine individual safety and efficacy end points.To determine whether an interaction exists between the presence of diabetes mellitus and treatment with everolimus-eluting stents compared with paclitaxel-eluting stents, we pooled the databases from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions (SPIRIT) II, SPIRIT III, SPIRIT IV, and A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice (COMPARE) trials in which percutaneous coronary intervention was performed in 6780 patients, 1869 (27.6%) of whom had diabetes mellitus. Patients without diabetes mellitus treated with everolimus-eluting stents compared with paclitaxel-eluting stents had significantly reduced 2-year rates of mortality (1.9% versus 3.1%; P=0.01), myocardial infarction (2.5% versus 5.8%; P<0.0001), stent thrombosis (0.3% versus 2.4%; P<0.0001), and ischemia-driven target lesion revascularization (3.6% versus 6.9%; P<0.0001). In contrast, among patients with diabetes mellitus, there were no significant differences between the 2 stent types in any measured safety or efficacy parameter. Significant interactions were present between diabetic status and stent type for the 2-year end points of myocardial infarction (P=0.01), stent thrombosis (P=0.0006), and target lesion revascularization (P=0.02).We have identified a substantial interaction between diabetes mellitus and stent type on clinical outcomes after percutaneous coronary intervention. In patients without diabetes mellitus, everolimus-eluting stents compared with paclitaxel-eluting stents resulted in substantial 2-year reductions in death, myocardial infarction, stent thrombosis, and target lesion revascularization, whereas no significant differences in safety or efficacy outcomes were present in diabetic patients.
Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men
Authors: Frederick C.W. Wu, Abdelouahid Tajar, Jennifer M. Beynon, Stephen R. Pye, Alan J. Silman, Joseph D. Finn, Terence W. O'Neill, Gyorgy Bartfai, Felipe F. Casanueva, Gianni Forti, Aleksander Giwercman, Thang S. Han, Krzysztof Kula, Michael E.J. Lean, Neil Pendleton, Margus Punab, Steven Boonen, Dirk Vanderschueren, Fernand Labrie, Ilpo T. Huhtaniemi
Journal: New England Journal of Medicine (2010)

The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level.
Efficacy of an oral appliance for the treatment of obstructive sleep apnea in a Brazilian population
Authors: Lilian Giannasi, Fernanda Almeida, Sergio Nacif, Israel Santos, Ismael Dias, Fernando Leitao Filho, Renato Pasqual, Luciana Sampaio, Rodolfo Vieira, Luis Oliveira
Journal: European Respiratory Journal (2013)

Aim: the aim of this prospective study was to validate, in Brazil, the use of an MRA to treat OSA and primary snoring, comparing polysomnographic and Epworth Sleepiness Scale (ESS) data obtained prior to and during MAS treatment. Method: this study was carried out on 63 patients presented with different OSA severity or primary snoring, who were fitted to PMPositioner® between 2009 and 2011. The diagnosis was established by a polysomnogram (PSG) prior treatment and a PSG after 6 month verified the efficacy of MRA therapy. Subjective daytime sleepness was evaluated by ESS questionnaire prior to treatment and at the follow up. Results: The sample was divided in primary snoring and OSA group. For the primary snoring group, PSG variables did not show significant results, except for snoring decreasing. For the OSA group the mean AHI has reduced from 23.0±11 to 5.3±4.0 (p≤0.001) and median ESS reduced significantly from 13.0(3-24) to 8.5(3-13). Complete response (AHI