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Antitrypsin

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https://www.readbyqxmd.com/read/29454662/fecal-markers-of-intestinal-inflammation-and-intestinal-permeability-are-elevated-in-parkinson-s-disease
#1
Andreas Schwiertz, Jörg Spiegel, Ulrich Dillmann, David Grundmann, Jan Bürmann, Klaus Faßbender, Karl-Herbert Schäfer, Marcus M Unger
BACKGROUND/OBJECTIVE: Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD. METHODS: In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay...
February 12, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29453277/editing-out-five-serpina1-paralogs-to-create-a-mouse-model-of-genetic-emphysema
#2
Florie Borel, Huaming Sun, Marina Zieger, Andrew Cox, Brynn Cardozo, Weiying Li, Gabriella Oliveira, Airiel Davis, Alisha Gruntman, Terence R Flotte, Michael H Brodsky, Andrew M Hoffman, Mai K Elmallah, Christian Mueller
Chronic obstructive pulmonary disease affects 10% of the worldwide population, and the leading genetic cause is α-1 antitrypsin (AAT) deficiency. Due to the complexity of the murine locus, which includes up to six Serpina1 paralogs, no genetic animal model of the disease has been successfully generated until now. Here we create a quintuple Serpina1a-e knockout using CRISPR/Cas9-mediated genome editing. The phenotype recapitulates the human disease phenotype, i.e., absence of hepatic and circulating AAT translates functionally to a reduced capacity to inhibit neutrophil elastase...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29448296/%C3%AE-2-macroglobulin-is-a-significant-in-vivo-inhibitor-of-activated-protein-c-and-low-apc-%C3%AE-2m-levels-are-associated-with-venous-thromboembolism
#3
Laura Martos, Luis Andrés Ramón, Julia Oto, Álvaro Fernández-Pardo, Santiago Bonanad, Ana Rosa Cid, Andras Gruber, John H Griffin, Francisco España, Silvia Navarro, Pilar Medina
BACKGROUND: Activated protein C (APC) is a major regulator of thrombin formation. Two major plasma inhibitors form complexes with APC, protein C inhibitor (PCI) and α 1 -antitrypsin (α 1 AT), and these complexes have been quantified by specific enzyme-linked immunosorbent assays (ELISAs). Also, complexes of APC with α 2 -macroglobulin (α 2 M) have been observed by immunoblotting. Here, we report an ELISA for APC:α 2 M complexes in plasma. METHODS: Plasma samples were pre-treated with dithiothreitol and then with iodoacetamide...
February 15, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29446109/systematic-review-the-natural-history-of-alpha-1-antitrypsin-deficiency-and-associated-liver-disease
#4
REVIEW
S A Townsend, R G Edgar, P R Ellis, D Kantas, P N Newsome, A M Turner
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is estimated to affect three million people worldwide. It causes liver disease in a proportion of carriers of the PiS and PiZ allele due to the formation and retention of polymers within the endoplasmic reticulum of hepatocytes. The reason for this selective penetrance is not known. Although clinical trials are underway, liver transplantation is the only effective treatment for liver disease due to AATD. AIMS: To report the prevalence and natural history of liver disease among individuals with AATD, and assess the outcomes of liver transplantation through systematic review...
February 15, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29445323/urine-proteomics-of-primary-membranous-nephropathy-using-nanoscale-liquid-chromatography-tandem-mass-spectrometry-analysis
#5
Lu Pang, Qianqian Li, Yan Li, Yi Liu, Nan Duan, Haixia Li
Background: Primary membranous nephropathy (PMN) is an important cause of nephrotic syndrome in adults. Urine proteome may provide important clues of pathophysiological mechanisms in PMN. In the current study, we analyzed and compared the proteome of urine from patients with PMN and normal controls. Methods: We performed two technical replicates (TMT1 and TMT2) to analyze and compare the urine proteome from patients with PMN and normal controls by tandem mass tag (TMT) technology coupled with nanoscale liquid chromatography tandem mass spectrometry analysis (LC-MS/MS)...
2018: Clinical Proteomics
https://www.readbyqxmd.com/read/29437593/%C3%AE-1-antitrypsin-infusion-for-treatment-of-steroid-resistant-acute-graft-versus-host-disease
#6
John M Magenau, Steven C Goldstein, Dan Peltier, Robert J Soiffer, Thomas Braun, Attaphol Pawarode, Mary M Riwes, Maggi Kennel, Joseph H Antin, Corey S Cutler, Vincent T Ho, Edwin P Alyea, Brian L Parkin, Gregory A Yanik, Sung Won Choi, Eli C Lewis, Charles A Dinarello, John Koreth, Pavan Reddy
Corticosteroid resistance following acute GVHD (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness due to poor response or excessive toxicity, primarily from infection. Alpha-1 antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by down-modulation of inflammation and increasing ratios of regulatory to effector T cells...
February 2, 2018: Blood
https://www.readbyqxmd.com/read/29434285/generation-of-a-dual-target-safe-inexpensive-microbicide-that-protects-against-hiv-1-and-hsv-2-disease
#7
Christina Farr Zuend, John F Nomellini, John Smit, Marc S Horwitz
HSV-2 infection is a significant health problem and a major co-morbidity factor for HIV-1 acquisition, increasing risk of infection 2-4 fold. Condom based prevention strategies for HSV-2 and HIV-1 have not been effective at stopping the HIV-1 pandemic, indicating that alternative prevention strategies need to be investigated. We have previously developed an inexpensive HIV-1 specific microbicide that utilizes the S-layer mediated display capabilities of Caulobacter crescentus, and have shown that recombinant C...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29432934/alpha-1-antitrypsin-deficiency-from-the-lung-to-the-heart
#8
Ivan Curjuric, Medea Imboden, Robert Bettschart, Seraina Caviezel, Julia Dratva, Marco Pons, Thomas Rothe, Arno Schmidt-Trucksäss, Daiana Stolz, Gian Andri Thun, Arnold von Eckardstein, Florian Kronenberg, Ilaria Ferrarotti, Nicole M Probst-Hensch
BACKGROUND AND AIMS: Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today. METHODS: Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design...
January 31, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29431403/mildly-elevated-liver-transaminase-levels-causes-and-evaluation
#9
Robert C Oh, Thomas R Hustead, Syed M Ali, Matthew W Pantsari
Mild, asymptomatic elevations (less than five times the upper limit of normal) of alanine transaminase and aspartate transaminase levels are common in primary care. It is estimated that approximately 10% of the U.S. population has elevated transaminase levels. An approach based on the prevalence of diseases that cause asymptomatic transaminase elevations can help clinicians efficiently identify common and serious liver disease. The most common causes of elevated transaminase levels are nonalcoholic fatty liver disease and alcoholic liver disease...
December 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/29430176/alpha-1-antitrypsin-to-treat-lung-disease-in-alpha-1-antitrypsin-deficiency-recent-developments-and-clinical-implications
#10
REVIEW
Kenneth R Chapman, Joanna Chorostowska-Wynimko, A Rembert Koczulla, Ilaria Ferrarotti, Noel G McElvaney
Alpha 1 antitrypsin deficiency is a hereditary condition characterized by low alpha 1 proteinase inhibitor (also known as alpha 1 antitrypsin [AAT]) serum levels. Reduced levels of AAT allow abnormal degradation of lung tissue, which may ultimately lead to the development of early-onset emphysema. Intravenous infusion of AAT is the only therapeutic option that can be used to maintain levels above the protective threshold. Based on its biochemical efficacy, AAT replacement therapy was approved by the US Food and Drug administration in 1987...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29427759/quantitative-analysis-of-core-fucosylation-of-serum-proteins-in-liver-diseases-by-lc-ms-mrm
#11
Junfeng Ma, Miloslav Sanda, Renhuizi Wei, Lihua Zhang, Radoslav Goldman
Aberrant core fucosylation of proteins has been linked to liver diseases. In this study, we carried out multiple reaction monitoring (MRM) quantification of core fucosylated N-glycopeptides of serum proteins partially deglycosylated by a combination of endoglycosidases (endoF1, endoF2, and endoF3). To minimize variability associated with the preparatory steps, the analysis was performed without enrichment of glycopeptides or fractionation of serum besides the nanoRP chromatography. Specifically, we quantified core fucosylation of 22 N-glycopeptides derived from 17 proteins together with protein abundance of these glycoproteins in a cohort of 45 participants (15 disease-free control, 15 fibrosis and 15 cirrhosis patients) using a multiplex nanoUPLC-MS-MRM workflow...
February 7, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29420065/role-for-cela1-in-postnatal-lung-remodeling-and-aat-deficient-emphysema
#12
Rashika Joshi, Andrea Heinz, Qiang Fan, Shuling Guo, Brett Monia, Christian E H Schmelzer, Anthony S Weiss, Matthew Batie, Harikrishnan Parameshwaran, Brian M Varisco
RATIONALE: α1-antitrypsin (AAT) deficiency-related emphysema is the fourth leading indication for lung transplantation. Chymotrypsin-like elastase 1 (Cela1) is a digestive protease that is expressed during lung development in association with regions of elastin remodeling, exhibits stretch-dependent expression during lung regeneration, and binds lung elastin in a stretch-dependent manner. AAT covalently neutralizes Cela1 in vitro. OBJECTIVES: We sought to determine the role of Cela1 in postnatal lung physiology, whether it interacted with AAT in vivo, and any effects it may have in the context of AAT deficiency...
February 8, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29419340/alpha-1-antitrypsin-a-novel-predictor-for-long-term-recovery-of-chronic-disorder-of-consciousness
#13
Wangxiao Bao, Fangping He, Jian Gao, Fanxia Meng, Hai Zou, Benyan Luo
BACKGROUND: The aim of this manuscript was to explore the molecular basis and identify novel biomarkers for the diagnosis and prognosis of patients with chronic disorder of consciousness. METHODS: A coupled isobaric tag for relative and absolute quantitation-based approach was used to screen differentially expressed proteins (DEPs) between patients with chronic disorder of consciousness and healthy individuals. Candidate proteins were identified and measured. The Coma Recovery Scale-Revised (CRS-R) score was used to quantify the severity, and long-term recovery was assessed by Glasgow Outcome Scale (GOS)...
February 8, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29417940/inverse-changes-in-plasma-tetranectin-and-titin-levels-in-patients-with-type-2-diabetes-mellitus-a-potential-predictor-of-acute-myocardial-infarction
#14
Mohd Aizat Abdul Rahim, Zubaidah Haji Abdul Rahim, Wan Azman Wan Ahmad, Marina Mohd Bakri, Muhammad Dzafir Ismail, Onn Haji Hashim
An early intervention using biomarkers to predict acute myocardial infarction (AMI) will effectively reduce global heart attack incidence, particularly among high-risk patients with type 2 diabetes mellitus (T2DM). This study attempted to identify potential biomarkers by detecting changes in the levels of plasma proteins in T2DM patients following onset of AMI in comparison with those without AMI. Volunteer T2DM patients without AMI (control; n=10) and T2DM patients with AMI (n=10) were recruited. Plasma samples from these patients were evaluated via two-dimensional gel electrophoresis (2DE) to screen for proteins with level changes between the two groups...
February 8, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29413345/association-between-%C3%AE-1-antitrypsin-and-bronchiectasis-in-patients-with-humoral-immunodeficiency-receiving-gammaglobulin-infusions
#15
Brian P Peppers, Jamie Zacharias, Chelsea R Michaud, John A Frith, Priya Varma, Mark Henning, Linda M Quinn, Haig Tcheurekdjian, Timothy Craig, Robert W Hostoffer
BACKGROUND: In patients with humoral immunodeficiency, the progression of bronchiectasis has been known to occur despite adequate gammaglobulin therapy and in the absence of recurrent infections. This observation suggests that factors other than gammaglobulin replacement might play a part in the prevention of lung damage in this population. α1-Antitrypsin deficiency can be associated with bronchiectasis, a chronic inflammatory lung disease. The protective levels of α1-antitrypsin and phenotype in preventing bronchiectasis have not been thoroughly studied in the immunodeficient population...
February 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29409945/billion-scale-production-of-hepatocyte-like-cells-from-human-induced-pluripotent-stem-cells
#16
Tomoki Yamashita, Kazuo Takayama, Fuminori Sakurai, Hiroyuki Mizuguchi
Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells are expected to be utilized in drug screening and regenerative medicine. However, hepatocyte-like cells have not been fully used in such applications because it is difficult to produce such cells on a large scale. In this study, we tried to establish a method to mass produce hepatocyte-like cells using a three-dimensional (3D) cell culture bioreactor called the Rotary Cell Culture System (RCCS). RCCS enabled us to obtain homogenous hepatocyte-like cells on a billion scale (>109 cells)...
February 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29408782/changes-of-cerebrospinal-fluid-protein-concentrations-and-gait-patterns-in-geriatric-normal-pressure-hydrocephalus-patients-after-ventriculoperitoneal-shunting-surgery
#17
Carl P C Chen, Yin-Cheng Huang, Chen-Nen Chang, Jean-Lon Chen, Chih-Chin Hsu, Wan-Ying Lin
Normal pressure hydrocephalus (NPH) was the first type of dementia ever described that can be treated using ventriculoperitoneal shunting surgery. Three typical clinical symptoms of NPH include gait disturbance, progressive cognitive dysfunction, and urinary incontinence. Although there are articles that have discovered several cerebrospinal fluid (CSF) protein biomarkers associated with NPH; however, studies examining individual and total protein concentrations from the ventricular CSF before and after shunting surgery are lacking...
February 1, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29406986/was-ugo-foscolo-1778-1827-affected-by-alpha-1-antitrypsin-deficiency
#18
A Perciaccante, C Negri, A Coralli, P Charlier, O Appenzeller, R Bianucci
Niccolò Ugo Foscolo (1778-1827), known as Ugo, is one of the masters of the Italian poetry. A writer and a revolutionary, he embraced the ideals of the French Revolution and took part in the stormy political discussions, which the fall of the Republic of Venice had provoked. Despite his poor health, Foscolo lived an adventurous life serving as a volunteer in the Guardia Nazionale and in the Napoleonic army. Following Napoleon's fall (1814), he went into voluntary exile in early 1815. He reached London in Sept...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29405331/the-analysis-of-alpha-1-antitrypsin-glycosylation-with-direct-lc-ms-ms
#19
Haidi Yin, Mingrui An, Puikin So, Melody Wong, David M Lubman, Zhongping Yao
A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methodology has been developed to differentiate core- and antennary-fucosylated glycosylation of glycopeptides. Both the glycosylation sites (heterogeneity) and multiple possible glycan occupancy at each site (microheterogeneity) can be resolved via intact glycopeptide analysis. The serum glycoprotein alpha-1-antitrypsin (A1AT) which contains both core- and antennary-fucosylated glycosites was used in this study. Sialidase was used to remove the sialic acids in order to simplify the glycosylation microheterogeneity and to enhance the MS signal of glycopeptides with similar glycan structures...
February 5, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29402641/-emphysema-did-you-say-emphysema
#20
J Benzaquen, J Pradelli, B Padovani, C H Marquette, S Leroy
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common condition that may initially look simple but may conceal other diseases capable of accelerating its natural history or even simulating it. We describe four cases presenting as COPD with emphysema that were reclassified on the basis of certain clinical characteristics and the radiological pattern. CASE REPORTS: A 52 year old never smoking woman presenting with emphysema was eventually diagnosed as having lymphangioleiomyomatosis on the basis of an abdominal CT scan showing kidney angiomyolipomas...
February 2, 2018: Revue des Maladies Respiratoires
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