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Yusuke Miyazaki, Yasufumi Katanasaka, Yoichi Sunagawa, Sae Hirano-Sunagawa, Masafumi Funamoto, Eriko Morimoto, Maki Komiyama, Akira Shimatsu, Noriko Satoh-Asahara, Hajime Yamakage, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
PURPOSE: HMG-CoA reductase inhibitors, also termed statins, are used to reduce the risk of coronary artery disease. Two oxidatively modified low-density lipoprotein (LDL) complexes, serum amyloid A-LDL (SAA-LDL) and α1-antitrypsin-LDL (AT-LDL), serve as atherosclerotic, inflammatory, and cardiovascular risk markers. In this study, we examined the effects of hydrophilic rosuvastatin (RSV) and lipophilic pitavastatin (PTV) on these markers in patients with hypercholesterolemia. METHODS: The present study was a sub-analysis of our previous STAT-LVDF study...
October 3, 2016: International Journal of Cardiology
L Renee Ruhaak
In recent years, high-throughput glycomics approaches have been developed and applied to either complete biofluids, cell lysates or tissues, or proteins isolated thereof. However, during such analyses the N-glycan are released from the protein backbone and therefore site- and protein-specific information is lost. There exists a need for high-throughput methods that allow quantification of site- and protein-specific glycosylation patterns from complex biological mixtures. We here describe the use of a multiple reaction monitoring mass spectrometry based method for the generation of glycopeptide profiles of the nine high abundance glycoproteins IgG, IgA, IgM, haptoglobin, alpha-1-antitrypsin, alpha-2-macroglobulin, alpha-1-acid glycoprotein, transferrin, and complement C3...
2017: Methods in Molecular Biology
T Dau, E V Edeleva, S A I Seidel, R A Stockley, D Braun, D E Jenne
High abundance proteins like protease inhibitors of plasma display a multitude of interactions in natural environments. Quantitative analysis of such interactions in vivo is essential to study diseases, but have not been forthcoming, as most methods cannot be directly applied in a complex biological environment. Here, we report a quantitative microscale thermophoresis assay capable of deciphering functional deviations from in vitro inhibition data by combining concentration and affinity measurements. We obtained stable measurement signals for the substrate-like interaction of the disease relevant inhibitor α-1-antitrypsin (AAT) Z-variant with catalytically inactive elastase...
October 14, 2016: Scientific Reports
I Tuleta, F Stöckigt, U R Juergens, C Pizarro, J W Schrickel, G Kristiansen, G Nickenig, D Skowasch
INTRODUCTION: Intermittent hypoxia as a surrogate of obstructive sleep apnea is associated with different cardiovascular complications. However, the effects of intermittent hypoxia on the lung tissue are less known. Therefore, the aim of our present study was to investigate if intermittent hypoxia may influence oxidative stress, inflammation, and protease/antiprotease system in the lung. Additionally, potential protective properties of anti-inflammatory and anti-oxidative drugs have been evaluated...
October 13, 2016: Lung
Henning Gram Hansen, Helene Faustrup Kildegaard, Gyun Min Lee, Stefan Stefan Kol
Accurate titer determination of recombinant proteins is crucial for evaluating protein production cell lines and processes. Even though enzyme-linked immunosorbent assay (ELISA) is the most widely used assay for determining protein titer, little is known about the accuracy of commercially available ELISA kits. We observed that estimations of recombinant human ø1-antitrypsin (rø1AT) titer by Coomassie-stained SDS-PAGE gels did not correspond to previously obtained titers obtained by a commercially available ELISA kit...
October 12, 2016: Biotechnology Journal
S Gilani, G S Howarth, S M Kitessa, C D Tran, R E A Forder, R J Hughes
Increased intestinal permeability (IP) can lead to compromised health in chickens. As there is limited literature on in vivo biomarkers to assess increased IP in chickens, the objective of this study was to identify a reliable biomarker of IP using DSS ingestion and fasting models. Male Ross chickens (n = 48) were reared until day 14 on the floor pen in an animal care facility, randomized into the following groups: control, DSS and fasting (each with n = 16), and then placed in metabolism cages. DSS was administered in drinking water at 0...
October 11, 2016: Journal of Animal Physiology and Animal Nutrition
Nupur Aggarwal, Beatriz Martinez Delgado, Sandeep Salipalli, Nerea Matamala, Jessica Rademacher, Nicolaus Schwerk, Tobias Welte, Sabina Janciauskiene, Felix C Ringshausen
Recurrent infections of the upper airways in early life may be a warning sign of inherited α1-antitrypsin deficiency
April 2016: ERJ Open Research
Kumar Kanishka, Anand Yogeshman, Jha Kumar Rajendra, Kachhap Sushil
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Anna Sroka-Bartnicka, Isabella Karlsson, Lorena Ndreu, Alessandro Quaranta, Matthijs Pijnappel, Gunnar Thorsén
Glycosylation is one of the most common and important post-translational modifications, influencing both the chemical and the biological properties of proteins. Studying the glycosylation of the entire protein population of a sample can be challenging because variations in the concentrations of certain proteins can enhance or obscure changes in glycosylation. Furthermore, alterations in the glycosylation pattern of individual proteins, exhibiting larger variability in disease states, have been suggested as biomarkers for different types of cancer, as well as inflammatory and neurodegenerative diseases...
October 3, 2016: Journal of Pharmaceutical and Biomedical Analysis
Limin Hao, Oshrit Ben-David, Suzann M Babb, Anthony H Futerman, Bruce M Cohen, Edgar A Buttner
Defining the mechanisms of action of the anti-psychotic drug (APD), clozapine is of great importance, as clozapine is more effective and has therapeutic benefits in a broader range of psychiatric disorders than other APDs. Its range of actions have not been fully characterized. Exposure to APDs early in development causes dose-dependent developmental delay and lethality in C. elegans. A previous genome-wide RNAi screen for suppressors of clozapine-induced developmental delay and lethality revealed 40 candidate genes, including sms-1, which encodes a sphingomyelin synthase...
October 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Nikolas Bernhard, Robert Bals, Sebastian Fähndrich
Alpha-1-antitrypsin deficiency is a genetic risk factor for the development of chronic obstructive airway disease (COPD) and liver cirrhosis. The disease is widely underdiagnosed. The hallmarks of therapy are smoking cessation, prevention from environmental dust exposure and augmentation therapy. Findings from the recently published prospective, placebo-controlled and randomized RAPID trial proved effectiveness of AAT augmentation therapy for slowing progression of emphysema, measured by CT lung density. CT lung density may be more sensitive than forced exspiratory volume in one second (FEV1) or monoxid diffusion capacity (DLCO)...
September 2016: Deutsche Medizinische Wochenschrift
Luis Sendra, Antonio Miguel, Daniel Pérez-Enguix, María José Herrero, Eva Montalvá, María Adelaida García-Gimeno, Inmaculada Noguera, Ana Díaz, Judith Pérez, Pascual Sanz, Rafael López-Andújar, Luis Martí-Bonmatí, Salvador F Aliño
INTRODUCTION: Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion. In the present study, two closed liver hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are compared to reference standards in order to evaluate their potential clinical interest...
2016: PloS One
Marcin Surmiak, Marek Sanak
BACKGROUND: One of characteristic findings in granulomatosis with polyangiitis (GPA) is the presence of proteinase-3 (anti-PR3) specific antibodies. These antibodies can cause neutrophil activation, degranulation and generation of reactive oxygen species (ROS). Each of these inflammatory events can be suppressed by circulating alpha-1 antitrypsin (A1AT). A1AT is an acute phase protein increasing during inflammation, however, it may circulate as an inactive polymeric protein. AIM OF THE STUDY: The aim was to analyze how different types of A1AT can affect anti-PR3 mediated neutrophil activation...
August 5, 2016: Pharmacological Reports: PR
Shih-Yi Lin, Chao-Hsiang Chang, His-Chin Wu, Ching-Chan Lin, Kai-Po Chang, Chi-Rei Yang, Chi-Ping Huang, Wu-Huei Hsu, Chiz-Tzung Chang, Chao-Jung Chen
MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96...
September 30, 2016: Scientific Reports
Inga Jarosch, Sebastian Gehlert, Daniel Jacko, Rembert Andreas Koczulla, Marion Wencker, Tobias Welte, Wilhelm Bloch, Sabina Janciauskiene, Klaus Kenn
BACKGROUND: Pulmonary rehabilitation (PR) improves oxidative capacity of peripheral muscles in patients with chronic obstructive pulmonary disease (COPD). The exercise-induced oxidative skeletal muscle adaptation in COPD patients with inherited alpha-1 antitrypsin deficiency (A1ATD) has not been studied. OBJECTIVES: To compare PR effects on skeletal muscle adaptation in COPD patients with and without A1ATD. METHODS: Nine COPD patients with A1ATD (genotype PiZZ, 6 receiving A1AT augmentation therapy), and 10 'usual' COPD patients (genotype PiMM) performed an incremental cycling test and underwent musculus vastus lateralis biopsies before and after a 3-week PR program including exercise training...
September 30, 2016: Respiration; International Review of Thoracic Diseases
Mark A Baker, Elena K Schneider, Johnny X Huang, Matthew A Cooper, Jian Li, Tony Velkov
Ertapenem is an important first-line carbapenem antibiotic used for the treatment of aerobic Gram-negative bacterial infections. It is the only carbapenem that is highly bound to plasma proteins and displays a concentration-dependent and saturable plasma protein binding profile. To date the plasma components responsible for sequestering ertapenems antibacterial activity remain uncharacterised. In the present study we have employed an orthogonal, multi-platform approach, including novel compound-centric displacement proteomics and Surface Plasmon Resonance to characterise the plasma protein binding proteome of ertapenem...
September 28, 2016: ACS Chemical Biology
Mardiaty Iryani Abdullah, Ching Chin Lee, Sarni Mat Junit, Khoon Leong Ng, Onn Haji Hashim
BACKGROUND: Papillary thyroid cancer (PTC) is mainly diagnosed using fine-needle aspiration biopsy. This most common form of well-differentiated thyroid cancer occurs with or without a background of benign thyroid goiter (BTG). METHODS: In the present study, a gel-based proteomics analysis was performed to analyse the expression of proteins in tissue and serum samples of PTC patients with (PTCb; n = 6) and without a history of BTG (PTCa; n = 8) relative to patients with BTG (n = 20)...
2016: PeerJ
Adel Boueiz, Sharon M Lutz, Michael H Cho, Craig P Hersh, Russell P Bowler, George R Washko, Eitan Halper-Stromberg, Per Bakke, Amund Gulsvik, Nan M Laird, Terri H Beaty, Harvey O Coxson, James D Crapo, Edwin K Silverman, Peter J Castaldi, Dawn L DeMeo
RATIONALE: Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. OBJECTIVES: To identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin deficient smokers...
September 26, 2016: American Journal of Respiratory and Critical Care Medicine
Benjamin T Porebski, Shani Keleher, Jeffrey J Hollins, Adrian A Nickson, Emilia M Marijanovic, Natalie A Borg, Mauricio G S Costa, Mary A Pearce, Weiwen Dai, Liguang Zhu, James A Irving, David E Hoke, Itamar Kass, James C Whisstock, Stephen P Bottomley, Geoffrey I Webb, Sheena McGowan, Ashley M Buckle
The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant...
September 26, 2016: Scientific Reports
Cristina Airoldi, Carlotta Ciaramelli, Marco Fumagalli, Rita Bussei, Valeria Mazzoni, Simona Viglio, Paolo Iadarola, Jan Stolk
The metabolomic analysis of exhaled breath condensate (EBC) may provide insights on both the pathology of pulmonary disorders and the response to therapy. This pilot study describes the ability of nuclear magnetic resonance (NMR)-based metabolomics to discriminate α1-antitrypsin deficient (AATD)-patients, who were diagnosed with moderate to severe emphysema, from healthy individuals. Comparative analysis of samples from these two homogeneous cohorts of individuals resulted in the generation of NMR profiles that were different from both a qualitative and a quantitative point-of-view...
October 5, 2016: Journal of Proteome Research
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