tbuckley/cabot-search huggingface dataset:
Montelukast Reduces Asthma Exacerbations in 2- to 5-Year-Old Children with Intermittent Asthma
Authors: Hans Bisgaard, Stefen Zielen, María Luz Garcia-Garcia, Sebastian L. Johnston, Leen Gilles, Joris Menten, Carol A. Tozzi, Peter Polos
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms, β-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2.34 episodes on placebo. Montelukast also delayed the median time to first exacerbation by approximately 2 months (p = 0.024), and the rate of inhaled corticosteroid courses (p = 0.027) compared with placebo. Montelukast effectively reduced asthma exacerbations in 2- to 5-year-old patients with intermittent asthma over 12 months of treatment and was generally well tolerated.
STUDIES ON THE RELATIONSHIP OF ALLOTYPIC SPECIFICITIES TO ANTIBODY SPECIFICITIES IN THE RABBIT
Authors: Ronald F. Rieder, Jacques Oudin
Journal: The Journal of Experimental Medicine (1963)

Purified antibodies against three different antigens and haptens (ovalbumin, dinitrophenol, and Type II pneumococcal polysaccharide) were prepared from specific precipitates from the antisera of several rabbits. The reactions of these preparations with antisera against the allotypic specificities carried by each of the animals forming the antibodies were used to compare the relative concentrations of molecules bearing each specificity in the different solutions of antibodies from each rabbit. These relative concentrations appeared to vary greatly from one preparation to another, although all the allotypic specificities carried by each animal were found in all the preparations of antibodies from that animal. The interpretation of these results is discussed.
Dynamic transport and localization of alpha-synuclein in primary hippocampal neurons
Authors: Mong-Lin Yang, Linda Hasadsri, Wendy S Woods, Julia M George
Journal: Molecular Neurodegeneration (2010)

Alpha-synuclein is a presynaptic protein with a proposed role in neurotransmission and dopamine homeostasis. Abnormal accumulation of alpha-synuclein aggregates in dopaminergic neurons of the substantia nigra is diagnostic of sporadic Parkinson's disease, and mutations in the protein are linked to early onset forms of the disease. The folded conformation of the protein varies depending upon its environment and other factors that are poorly understood. When bound to phospholipid membranes, alpha-synuclein adopts a helical conformation that mediates specific interactions with other proteins.To investigate the role of the helical domain in transport and localization of alpha-synuclein, eGFP-tagged constructs were transfected into rat primary hippocampal neurons at 7 DIV. A series of constructs were analyzed in which each individual exon was deleted, for comparison to previous studies of lipid affinity and alpha-helix content. A53T and A30P substitutions, representing Parkinson's disease-associated variants, were analyzed as well. Single exon deletions within the lipid-binding N-terminal domain of alpha-synuclein (exons 2, 3, and 4) partially disrupted its presynaptic localization at 17-21 DIV, resulting in increased diffuse labeling of axons. Similar results were obtained for A30P, which exhibits decreased lipid binding, but not A53T. To examine whether differences in presynaptic enrichment were related to deficiencies in transport velocity, transport was visualized via live cell microscopy. Tagged alpha-synuclein migrated at a rate of 1.85 +/- 0.09 mum/s, consistent with previous reports, and single exon deletion mutants migrated at similar rates, as did A30P. Deletion of the entire N-terminal lipid-binding domain (Delta234GFP) did not significantly alter rates of particle movement, but decreased the number of moving particles. Only the A53TGFP mutant exhibited a significant decrease in transport velocity as compared to ASGFP.These results support the hypothesis that presynaptic localization involves a mechanism that requires helical conformation and lipid binding. Conversely, the rate of axonal transport is not determined by lipid affinity and is not sufficient to account for differences in presynaptic localization of alpha-synuclein-eGFP variants.
Marked Reduction in Percentage of Rosette-Forming Thymocytes of Rats During Induction of Bladder Tumors and Restorative Effect of Thymosin In Vitro2
Authors: Shuhel Kimura, Yukichi Ozaki, Tateru Toyokawa, Shoichi Nishio, Masanobu Maekawa, Allan L. Goldstein, Yoshlhiro Kinoshita
Journal: JNCI Journal of the National Cancer Institute (1986)

Urinary bladder carcinoma was induced in W rats by oral administration of N-butyl-N-(4-hydroxybutyl) nitrosamine [(BBN) CAS: 3817-11-6], and rosette formation of the thymus lymphocytes with Hartley strain guinea pig erythrocytes was studied until the 20th week after BBN administration. Percentage of rosette-forming cells (RFC's) began to decrease about the 8th week (stage of hypertrophy or vascular formation in the bladder wall) and remarkably declined around the 12th week (before the incidence of carcinoma) after the administration. However, no significant reduction of RFC percentage was noted in the control (without BBN) group during the observation period. Pretreatment of thymic lymphocytes from BBN-treated rats with thymosin fraction 5 (TF5), an extract from calf thymus, significantly enhanced the percentage of RFC near to that of the control level. Two (#9 and 13) subfractions separated from TF5 by high-performance liquid chromatography were found to be more effective in recovering the percentage of RFC. These results show that a maturational impairment of thymus lymphocytes may be caused from precancerous stage in BBN-administered rats and that this impairment would be restored by the thymus products in vitro.
Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell lymphoma: Clinical relevance in 71 patients
Authors: U Vitolo, G Gaidano, B Botto, G Volpe, E Audisio, M Bertini, R Calvi, R Freilone, D Novero, L Orsucci, C Pastore, D Capello, G Parvis, C Sacco, V Zagonel, A Carbone, U Mazza, G Palestro, G Saglio, L Resegotti
Journal: Annals of Oncology (1998)
Human lymphocyte surface immunoglobulin capping. Normal characteristics and anomalous behavior of chronic lymphocytic leukemic lymphocytes.
Authors: H J Cohen
Journal: Journal of Clinical Investigation (1975)

The phenomenon of redistribution of surface membrane immunoglobulin (Ig) components (capping) has been well described in mouse lymphoid cells. The characteristics of this process in human lymphocytes are less clear. This study characterizes the phenomenon of surface membrane Ig redistribution of normal and chronic lymphocytic leukemia (CLL) lymphocytes with the use of fluoroscein-labeled anti-Ig sera. Normal lymphocytes underwent rapid cap formation after incubation with anti-Ig serum in the cold and subsequent rewarming. The morphology was characteristic with aggregation over the pole of the cell opposite the nucleus and over the uropod when present. The process was energy dependent but independent of protein synthesis, and could be inhibited by vincristine, vinblastine, and colchicine but not by cytochalasin B. CLL cells, on the other hand, though showing fluorescent complex aggregation on the surface, rarely demonstrated unidirectional movement of these aggregates to form a cap. Cap formation in these cells could not be stimulated by supplementing the energy source or protein concentration of the medium nor by adding glutamic acid which could partially reverse the vincristine and vinblastine inhibition of normal capping. The failure of agents which inhibit motility to inhibit capping of the normal lymphocytes suggests that active locomotion is not a direct prerequisite for capping. The results also suggest the involvement of microtubules in normal capping and the possibility that abnormal membrane structure or microtubular function could explain the failure of CLL cells to behave normally in this regard. The role of this cellular defect in the immune deficiencies exhibited by many patients with CLL, however, is not established.
Molecular Genetics of Allergic Diseases
Authors: Santa Jeremy Ono
Journal: Annual Review of Immunology (2000)

Allergic diseases affect approximately one third of the general population. This class of disease, characterized by elevated serum IgE levels and hypersensitivity to normally innocuous antigen, can manifest in practically any mucosal tissue or as a systemic response. A few examples of serious allergic diseases include asthma, dermatitis, bee sting allergy, food allergy, conjunctivitis, and severe systemic anaphylaxis. Taken together, allergic diseases constitute one of the major problems of modern day medicine. A considerable portion of the healthcare budget is expended in the treatment of allergic disease, and morbidity rates of inner city asthmatics are rising steadily. Due to the enormity of the problem, there has been a worldwide effort to identify factors that contribute to the etiology of allergic diseases. Epidemiologic studies of multigeneration families and large numbers of twins clearly indicate a strong genetic component to atopic diseases. At least two independently segregating diseasesusceptibility genes are thought to come together with environmental factors to result in allergic inflammation in a particular tissue. On the basis of the strong genetic studies, multiple groups have attempted to identify disease-susceptibility genes via either a candidate gene approach or by genome-wide scans. Both of these approaches have implicated multiple regions in the human and mouse genomes, which are currently being evaluated as harboring putative atopy genes.
Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants
Authors: M. May, P. Strobel, T. Preisshofen, S. Seidenspinner, A. Marx, C.P. Speer
Journal: European Respiratory Journal (2004)

Apoptosis and proliferation and the effect of exogenous surfactant on these processes were investigated in the lungs of mechanically ventilated/oxygen-treated preterm infants with respiratory distress syndrome and stillborn foetuses. Apoptotic and proliferation indices were determined in lung tissue sections from 27 ventilated/oxygen-treated preterm infants and 29 stillborn foetuses. The effect of exogenous surfactant on apoptosis and proliferation was studied in 16 ventilated preterm infants; 11 untreated infants served as control. Apoptotic and proliferating cells were identified by double labelling combining terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end-labelling or Ki-67 with cell marker proteins. Pathways to cell death were explored by immunolabelling of cleaved caspases-3, -8 and -9. In the lungs of ventilated/oxygen-treated preterm infants, the numbers of apoptotic and proliferating cells increased significantly compared to the respective numbers in the lungs of stillborn foetuses. Apoptosis was detected in alveolar epithelial cells, whereas epithelial, endothelial and smooth muscle cells proliferated. Surfactant treatment reduced apoptosis induced by ventilation/oxygen-treatment; however, the decrease was not significant. Caspases-8 and -9 do not contribute to ventilation-induced apoptosis, whereas caspase-3 is involved. In conclusion, ventilation/oxygen-treatment induces epithelial cell apoptosis and proliferation of epithelial, endothelial and smooth muscle cells in the lungs of preterm infants.
Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people
Authors: Anoop Dinesh Shah, Claudia Langenberg, Eleni Rapsomaniki, Spiros Denaxas, Mar Pujades-Rodriguez, Chris P Gale, John Deanfield, Liam Smeeth, Adam Timmis, Harry Hemingway
Journal: The Lancet Diabetes & Endocrinology (2014)

BackgroundThe contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.MethodsWe used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439).FindingsOur cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1–10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76–3·22]), ischaemic stroke (1·72 [1·52–1·95]), stable angina (1·62 [1·49–1·77]), heart failure (1·56 [1·45–1·69]), and non-fatal myocardial infarction (1·54 [1·42–1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35–0·59]) and subarachnoid haemorrhage (0·48 [0·26–0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76–1·19]).InterpretationHeart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design.FundingWellcome Trust, National Institute for Health Research, and Medical Research Council.
Association between depression and risk of atrial fibrillation and stroke in patients with psoriasis: a Danish nationwide cohort study
Authors: A. Egeberg, U. Khalid, G.H. Gislason, L. Mallbris, L. Skov, P.R. Hansen
Journal: British Journal of Dermatology (2015)

Psoriasis and depression are associated with atrial fibrillation (AF) and stroke, but the influence of depression on the risk of stroke and AF in patients with psoriasis has not been examined.We investigated the impact of depression on the risk of stroke and AF in patients with psoriasis in a nationwide cohort.Data on all Danish citizens aged ≥ 18 years between 1 January 1997 and 31 December 2011 (n = 5 251 888) were linked at the individual level in nationwide registers. Incidence rates (IRs) per 1000 person-years were calculated, and hazard ratios (HRs) adjusted for age, sex, concomitant medication and comorbidity were estimated by multivariate Cox regression models.There were 56,496 and 11,357 incident cases of mild and severe psoriasis, respectively. Incident depression occurred among 12,788 cases with mild and 3261 cases with severe psoriasis. IRs per 1000 patient-years of AF were 3·21, 5·02, 8·41, 5·39 and 7·41; and IRs of stroke were 2·62, 3·09, 6·71, 3·62 and 9·03 for the reference population, mild psoriasis without depression, mild psoriasis with depression, severe psoriasis without depression and severe psoriasis with depression, respectively. The respective HRs for new-onset AF were 1·14 [95% confidence interval (CI) 1·08-1·33], 1·19 (95% CI 1·06-1·33), 1·32 (95% CI 1·15-1·53) and 1·74 (95% CI 1.43-2·11), respectively. For stroke the HRs were 1·63 (95% CI 1·43-1·85) in patients with mild psoriasis and depression and 2·47 (95% CI 2·07-2·95) in patients with severe psoriasis and depression.In patients with psoriasis, depression is associated with an increased risk of incident AF and stroke.
Pulmonary vascular resistances during exercise in normal subjects: a systematic review
Authors: G. Kovacs, A. Olschewski, A. Berghold, H. Olschewski
Journal: European Respiratory Journal (2011)

The physiological range of pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR), and the impact of exercise, age and posture have been a matter of debate for many years. We performed a systematic literature review including all right heart catheterisation data where individual PVR and TPR of healthy subjects both at rest and exercise were available. Data were stratified according to age, exercise level and posture. Supine resting PVR in subjects aged &lt;24 yrs, 24–50 yrs, 51–69 yrs and ≥70 yrs was 61±23, 69±28, 86±15 and 90±39 dyn·s·cm −5 , respectively. Corresponding TPR was 165±50, 164±46, 226±64 and 223±45 dyn·s·cm −5 , respectively. During moderate exercise in subjects aged ≤50 yrs, an 85% increase in cardiac output was associated with a 25% decrease in TPR (p&lt;0.0001) and a 12% decrease in PVR (p&lt;0.01). At 51–69 yrs of age there was no significant decrease in TPR and PVR. In individuals aged ≥70 yrs TPR even increased by 17% (p=0.01), while PVR did not change significantly. At higher exercise levels, TPR decreased in all age groups. In the upright position, based on a limited number of data, resting TPR and PVR were higher than in the supine position and decreased more prominently during exercise, suggesting the release of resting pulmonary vasoconstriction. These data may form a basis to define normal PVR at rest and exercise.
Women are more susceptible to anti-tobacco campaign than men
Authors: Marie-Dominique Dautzenberg, Bertrand Dautzenberg
Journal: European Respiratory Journal (2013)

In randomized trials one-year efficacy of NRT/placebo is lower among women because the placebo arm provide better results in women and NRT better results in male. It was the same with bupropion and varenicline cause near twice more nausea in female. We assessed in France the effect according to gender of non-gender oriented political decisions and campaigns.  Methods: The gender ratio variation was observed on the first attend to tobacco cessation service in smoker using internet service to stop and in Parisian high school last 10 years. During this period anti-tobacco activities has been very high in 2003 with the war against tobacco of France, then activity has been very low after 2007 because of governmental decisions.  Results: In France there are 7.5 million men who daily smoke (32%) and 6 million women (26%). Without any action, while women account for only 45% of smokers, women are more than 50% to call quitlines, 52% to attend tobacco cessation service and 60% of smoker who ask support to the internet coaching service.  In 2003, a strong anti-tobacco activity period, we observed an increase ratio of woman attending smoking clinic (50% to 54%). But 5 years later with the end of tobacco, control gender ratio dropped to 48%.  The 2003 campaigns led to an absolute decline among teenagers in smoking absolute rates of 7.6% for girls and 3.2% for boys. Unlike five years later abandoning the prevention of smoking among teenagers has been associated with a rise in smoking rate higher among girls (4.1%) than boys (3.4%).  Conclusion: If women are less sensitive to drugs, for smoking cessation they are more sensitive to campaigns and political decision whether adults or teenagers, even if campaigns are not targeted on gender.
Thrombopoietin Protects Against In Vitro and In Vivo Cardiotoxicity Induced by Doxorubicin
Authors: Karen Li, Rita Yn Tz Sung, Wei Zhe Huang, Mo Yang, Nga Hin Pong, Shuk Man Lee, Wood Yee Chan, Hailu Zhao, Man Yin To, Tai Fai Fok, Chi Kong Li, Yuek Oi Wong, Pak Cheung Ng
Journal: Circulation (2006)

Background— Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. Methods and Results— In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 μg/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. Conclusions— These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.
High-Dose Cisplatin and Dacarbazine in the treatment of Metastatic Melanoma
Authors: S. M. Luger, J. M. Kirkwood, M. S. Ernstoff, D. R. Vlock
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article High-Dose Cisplatin and Dacarbazine in the treatment of Metastatic Melanoma Get access Selina M. Luger, Selina M. Luger Division of Medical Oncology, Pittsburgh Cancer Institute, University of Pittsburgh School of MedicinePittsburgh, Pa. Search for other works by this author on: Oxford Academic PubMed Google Scholar John M. Kirkwood, John M. Kirkwood Division of Medical Oncology, Pittsburgh Cancer Institute, University of Pittsburgh School of MedicinePittsburgh, Pa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marc S. Ernstoff, Marc S. Ernstoff Division of Medical Oncology, Pittsburgh Cancer Institute, University of Pittsburgh School of MedicinePittsburgh, Pa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel R. Vlock Daniel R. Vlock * Division of Medical Oncology, Pittsburgh Cancer Institute, University of Pittsburgh School of MedicinePittsburgh, Pa. *Correspondence to : Daniel R. Vlock, MD, Hematology/Oncology, VA Medical Center, University Dr C, Pittsburgh, PA 15240. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 24, 19 December 1990, Pages 1934–1937, https://doi.org/10.1093/jnci/82.24.1934 Published: 19 December 1990 Article history Received: 01 August 1990 Revision received: 27 September 1990 Accepted: 01 October 1990 Published: 19 December 1990