Expression of CD44 and integrins in bronchial mucosa of normal and mildly asthmatic subjects

We have investigated the expression of cell surface markers and leucocyte cell adhesion molecules by immunohistochemistry in bronchial biopsies from 10 mild atopic asthmatics and 8 normal, nonatopic subjects. Significantly increased numbers of eosinophils (p<0.01) were evident in the bronchial submucosa of asthmatic subjects. In epithelium there were more CD44+ (p<0.02) and lymphocyte function-associated antigen-1 (LFA-1)+ (p<0.06) leucocytes in asthmatics than in normal subjects. Bronchial epithelial cells stained positively with anti-CD44 monoclonal antibodies (moAb) in both groups; however, when the staining was expressed as percentage of the total basement membrane, a considerable and highly significant increase was observed in the asthmatics (median 80 vs 22%, p=0.003). Few leucocytes were positive for very late activation antigen (VLA)-1, VLA-2 and VLA-4. The moAb for VLA-6 stained the basement membrane of the bronchial epithelium; while intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were constitutively expressed in endothelium. A positive correlation was found between LFA-1+ cells and activated eosinophils (EG2+) in the submucosa (p<0.005; r(s)=0.80). We conclude that even in mild asthma there is evidence of increased expression of cell surface ligands, and suggest that adhesive mechanisms play a role both in cell recruitment and disease activity.peer-reviewe

Istraživanje osnovnih parametara mehanizacije u cilju unapređenja proizvodnje, uštede energije i očuvanja životne sredine u poljoprivredi

Project 12M12 is realized in the scope of ten subproject in accordance with program, which is defined by agreement of ministry for period 1996-2000. There were about 120 scouter included in started year and about 80 scouter in final year. 911 papers were published in domestic or foreign journals or on scientific meetings. 25 monographs were published and 5 dissertation and 5 M. Sc. thesis were defended in the scope of project based on research. The situation of agricultural technique has been researched, necessities have been estimated and directions of development of power machines, tractors, processing technique, agricultural machines, vegetable production, animal husbandry, fruit growing, viticulture, mechanization for production salutary, spices and aromatic plants have been defined. The available methods have been advanced and the new methods have been developed for selection and forming tractor's systems and optimization structure and composition of engineering park in the agriculture. The soil compaction has been researched and changes have been established under effect of tractor's wheels, machines and transport vehicles and criterions have been set for reduction and supervision of soil compaction. The damages, appeared because of overmuch compaction, were estimated on 250- 300 USA $/ha per year. The new methods and equipment for prescience pull of tractor have been recommended. The powerful factors of fuel consumption have been affirmed and technology for production and reliance of alternative fuels (bio-diesel and generator gas) have been defined. The reliability of tractors and machines has been researched. The new and available technology and technical solutions of working of the soil, seeding and planting, mechanical and chemical care, collecting, finishing and storage agricultural products have been developed and reformed. The probability of application of sceaning method, method finalled elements, regression analysis, multicriterion optimization, fuzzy logic and neuron's networks, numeric analysis and others methods in process of outlay, projecting and concurring the new settlements of agricultural machines have been researched.Projekat Ministarstva nauke Republike Srbije, br. 12M12 realizovan je u okviru deset potprojekata prema programu koji je definisan ugovorom sa ministarstvom za period 1996-2000. godine. U izradi projekta učestvovalo je oko 120 istraživača u početnoj godini i oko 80 u završnoj godini. Objavljeno je 911 radova u domaćim ili inostranim časopisima ili na naučnim skupovima. Na osnovu istraživanja u okviru projekta objavljeno je 25 monografija i odbranjeno pet doktorskih i pet magistarskih teza. Istraženo je stanje poljoprivredne tehnike, procenjene potrebe i definisani pravci razvoja pogonskih mašina, traktora, procesne tehnike, mehanizacije u ratarstvu, povrtarstvu, stočarstvu, voćarstvu, vinogradarstvu, mehanizacije za proizvodnju lekovitog, začinskog i aromatičnog bilja. Unapređene su postojeće i razvijene nove metode za izbor i formiranje traktorskih sistema i optimizaciju strukture i sastav mašinskog parka u poljoprivredi. Istraživano je sabijanje zemljišta i utvrđene su promene nastale pod dejstvom točkova traktora, mašina i transportnih vozila i predložene su mere za smanjenje i kontrolu sabijanja. Procenjene su štete nastale usled prekomernog sabijanja zemljišta od 250 do 300 USA$/ha godišnje. Predložene su nove metode i oprema za predviđanje vuče traktora na van putnim podlogama. Utvrđeni su uticajni faktori na potrošnju goriva i maziva i definisana je tehnologija za proizvodnju i korišćenje alternativnih goriva (biodizel i prirodni gas). Istraživana je pouzdanost traktora i mašina. Razvijene su nove ili poboljšane postojeće tehnologije i nova ili poboljšana tehnička rešenja u obradi zemljišta, setvi i sadnji, mehaničkoj i hemijskoj nezi, ubiranju, doradi i čuvanju poljoprivrednih proizvoda. Istražena je mogućnost primene metoda skeniranja, metoda konačnih elemenata, regresione analize, višekriterijumske optimizacije, fuzzy logike i neuronskih mreža, numeričke analize i drugih metoda u procesu proračuna, projektovanja i osvajanja novih rešenja poljoprivrednih mašina

Одностадийный способ получения бифункционального древесного угля и изучение его свойств

Single-stage process of obtaining active carbon by thermal processing of plant raw materials (mixture of different types of wood sawdust) impregnated with the mixture of phosphoric acid, urea and nitric acid salts has been developed. Active influence of impregnates on the process of carbonization and formation of carbon residue has been demonstrated. It is established that carbon residue obtained in the interval of heating 20–700 °С possesses high sorption activity to the vapors of organic compounds and has ion-exchange capacity. It has been shown that the value of carbon residue depending on the impregnate used in the wood increases by 3,1 times at 600 °С and by 4,2 times – at 700 °С as compared to the yield of non-treated initial raw materials.Разработан одностадийный процесс получения активного угля путем термической переработки растительного сырья (опилок смеси различных пород древесины), пропитанного смесью ортофосфорной кислоты, карбамида и солей азотной кислоты. Показано активное влияние импрегнатов на процесс углефикации и порообразования углеродного остатка. Установлено, что углеродный остаток, полученный в интервале нагрева 20–700 °С, обладает высокой сорбционной активностью к парам органических соединений и имеет ионообменную емкость. Показано, что величина углеродного остатка в зависимости от используемого в древесине импрегната возрастает по сравнению с выходом необработанного исходного сырья в 3,1 раза при 600 °С и в 4,2 раза при 700 °С

GLACE: the global land–atmosphere coupling experiment. Part I: overview

Permission to place copies of these works on this server has been provided by the American Meteorological Society (AMS). The AMS does not guarantee that the copies provided here are accurate copies of the published work. © Copyright 2006 American Meteorological Society (AMS). Permission to use figures, tables, and brief excerpts from this work in scientific and educational works is hereby granted provided that the source is acknowledged. Any use of material in this work that is determined to be “fair use” under Section 107 of the U.S. Copyright Act or that satisfies the conditions specified in Section 108 of the U.S. Copyright Act (17 USC §108, as revised by P.L. 94-553) does not require the AMS’s permission. Republication, systematic reproduction, posting in electronic form on servers, or other uses of this material, except as exempted by the above statement, requires written permission or a license from the AMS. Additional details are provided in the AMS Copyright Policy, available on the AMS Web site located at (http://www.ametsoc.org/AMS) or from the AMS at 617-227-2425 or [email protected] Global Land–Atmosphere Coupling Experiment (GLACE) is a model intercomparison study focusing on a typically neglected yet critical element of numerical weather and climate modeling: land–atmosphere coupling strength, or the degree to which anomalies in land surface state (e.g., soil moisture) can affect rainfall generation and other atmospheric processes. The 12 AGCM groups participating in GLACE performed a series of simple numerical experiments that allow the objective quantification of this element for boreal summer. The derived coupling strengths vary widely. Some similarity, however, is found in the spatial patterns generated by the models, with enough similarity to pinpoint multimodel “hot spots” of land–atmosphere coupling. For boreal summer, such hot spots for precipitation and temperature are found over large regions of Africa, central North America, and India; a hot spot for temperature is also found over eastern China. The design of the GLACE simulations are described in full detail so that any interested modeling group can repeat them easily and thereby place their model’s coupling strength within the broad range of those documented here

Breathomics can discriminate between anti IgE-treated and non-treated severe asthma adults

Rationale: Omalizumab, an anti-IgE monoclonal antibody, is indicated in adults with severe persistent allergic asthma. Exhaled molecular markers can provide phenotypic information in asthma. Objectives: Determine whether adults with severe asthma on omalizumab (anti-IgE+) have a different breathprint compared with those who were not on anti-IgE therapy (anti-IgE-) as assessed by eNoses and gas chromatography/mass spectrometry (GC/MS) (breathomics). Methods: This was a cross-sectional analysis of the U- BIOPRED adult cohort. Severe asthma was defined by IMI-criteria [Bel, Thorax 2011]. Anti-IgE+ patients were on a regular treatment with s.c. omalizumab (150-375 mg) every 2-4 weeks. Exhaled volatile compounds trapped on adsorption tubes were analysed by a centralized eNose platform (Owlstone Lonestar, two Cyranose 320, Comon Invent, Tor Vergata TEN), including a total of 190 sensors, and GC/MS. Recursive feature elimination (http://topepo.github.io/caret/rfe.html) was used for feature selection and random forests, more robust to overfitting, for classification. Results: 9 anti- IgE+ (females/males 2/7, age 52.6±16.3 years, mean±SD, 1/2/6 current/ex/nonsmokers, pre-bronchodilator FEV1 70.6±21.1% predicted value) and 30 anti-IgE- patients (18/12 females/males, age 53.2±14.2 years, 0/16/14 current/ex/nonsmokers, pre-bronchodilator FEV1 59.6±30.7% predicted value) were studied. Conclusions: Preliminary results suggest that breathomics can distinguish between anti-IgE+ and anti-IgE- severe asthma patients

Dehydroepiandrosterone inhibits the progression phase of mammary carcinogenesis by inducing cellular senescence via a p16-dependent but p53-independent mechanism

INTRODUCTION: Dehydroepiandrosterone (DHEA), an adrenal 17-ketosteroid, is a precursor of testosterone and 17β-estradiol. Studies have shown that DHEA inhibits carcinogenesis in mammary gland and prostate as well as other organs, a process that is not hormone dependent. Little is known about the molecular mechanisms of DHEA-mediated inhibition of the neoplastic process. Here we examine whether DHEA and its analog DHEA 8354 can suppress the progression of hyperplastic and premalignant (carcinoma in situ) lesions in mammary gland toward malignant tumors and the cellular mechanisms involved. METHODS: Rats were treated with N-nitroso-N-methylurea and allowed to develop mammary hyperplastic and premalignant lesions with a maximum frequency 6 weeks after carcinogen administration. The animals were then given DHEA or DHEA 8354 in the diet at 125 or 1,000 mg/kg diet for 6 weeks. The effect of these agents on induction of apoptosis, senescence, cell proliferation, tumor burden and various effectors of cellular signaling were determined. RESULTS: Both agents induced a dose-dependent decrease in tumor multiplicity and in tumor burden. In addition they induced a senescent phenotype in tumor cells, inhibited cell proliferation and increased the number of apoptotic cells. The DHEA-induced cellular effects were associated with increased expression of p16 and p21, but not p53 expression, implicating a p53-independent mechanism in their action. CONCLUSION: We provide evidence that DHEA and DHEA 8354 can suppress mammary carcinogenesis by altering various cellular functions, inducing cellular senescence, in tumor cells with the potential involvement of p16 and p21 in mediating these effects

Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort

Background: Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures. Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE. Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively

Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD

Background: Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-β is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-β1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. Methods: In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). Results: In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001–placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. Conclusions: Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. Trial registration: EU clinical trials register (2017-003679-75), 6 October 2017

What bothers severe asthma patients most? A paired patient-clinician study across seven European countries

Introduction: Severe asthma is a complex, multi-dimensional disease. Optimal treatment adherence and outcomes require shared decision-making, rooted in mutual understanding between patient and clinician. This study used a novel, patient-centred approach to examine the most bothersome aspects of severe asthma to patients, as seen from both perspectives in asthma registries. Methods: Across seven countries, 126 patients with severe asthma completed an open-ended survey regarding most bothersome aspect(s) of their asthma. Patients’ responses were linked with their treating clinician who also completed free-text survey about each patient's most bothersome aspect(s). Responses were coded using content analysis, and patient and clinician responses were compared. Finally, asthma registries that are part of the SHARP Clinical Research Collaboration were examined to see the extent to which they reflected the most bothersome aspects reported by patients. Results: Eighty-eight codes and 10 themes were identified. Clinicians were more focused on direct physical symptoms and were less focused on ‘holistic’ aspects such as the effort required to self-manage their disease. Clinicians accurately identified a most bothersome symptom for 29% of patients. Agreement was particularly low in younger patients and those infrequently using oral corticosteroids. In asthma registries, patient aspects were predominantly represented in questionnaires. Conclusions: Results demonstrated different perspectives and priorities between patients and clinicians, with clinicians more focused on physical aspects. These differences must be considered when treating individual patients, and within multi-disciplinary treatment teams. The use of questionnaires that include multi-faceted aspects of disease may result in improved asthma research

Stratification of asthma phenotypes by airway proteomic signatures

© 2019 Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies