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https://www.readbyqxmd.com/read/29655560/selected-reaction-monitoring-mass-spectrometry-of-mastitis-milk-reveals-pathogen-specific-regulation-of-bovine-host-response-proteins
#1
Ulrike Kusebauch, Lorenzo E Hernández-Castellano, Stine L Bislev, Robert L Moritz, Christine M Røntved, Emøke Bendixen
Mastitis is a major challenge to bovine health. The detection of sensitive markers for mastitis in dairy herds is of great demand. Suitable biomarkers should be measurable in milk and should report pathogen-specific changes at an early stage to support earlier diagnosis and more efficient treatment. However, the identification of sensitive biomarkers in milk has remained a challenge, in part due to their relatively low concentration in milk. In the present study, we used a selected reaction monitoring (SRM) mass spectrometry approach, which allowed the absolute quantitation of 13 host response proteins in milk for the first time...
April 11, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29651215/plasma-neutrophil-elastase-%C3%AE-1-antitrypsin-%C3%AE-2-macroglobulin-and-neutrophil-elastase-%C3%AE-1-antitrypsin-complex-levels-in-patients-with-dengue-fever
#2
Mamatha Kunder, V Lakshmaiah, A V Moideen Kutty
Dengue fever (DF) is characterized by systemic inflammatory response including neutrophil activation leading to uncontrolled elastase activity. This study was aimed to measure the activity of plasma neutrophil elastase (NE), its endogenous inhibitors α1 -antitrypsin (α1 -AT) and α2 -macroglobulin (α2 -MG) and elastase in complex with α1 -AT (NE-α1 -AT complex) in DF. 50 dengue patients [39 DF and 11 dengue hemorrhagic fever (DHF)] and 52 healthy subjects were included in the study. NE was measured using N -succinyl-tri-alanine- p -nitroanilide as substrate...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29626713/differentiation-of-hepatocyte-like-cells-from-human-pluripotent-stem-cells-using-small-molecules
#3
Faizal Z Asumda, Konstantinos E Hatzistergos, Derek M Dykxhoorn, Silvia Jakubski, Jasmine Edwards, Emmanuel Thomas, Eugene R Schiff
A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives...
March 27, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29625713/are-there-differences-between-the-available-treatments-for-emphysema-associated-with-alpha-1-antitrypsin-deficiency
#4
Cristina Esquinas, Marc Miravitlles
No abstract text is available yet for this article.
April 3, 2018: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/29620600/environmental-enteropathy-micronutrient-adequacy-and-length-velocity-in-nepalese-children-the-mal-ed-birth-cohort-study
#5
Marianne S Morseth, Sigrun Henjum, Catherine Schwinger, Tor A Strand, Sanjaya K Shrestha, Binob Shrestha, Ram K Chandyo, Manjeswori Ulak, Liv Elin Torheim
OBJECTIVES: Environmental enteropathy (EE) is likely associated with growth retardation in children, but the association between EE and length velocity z-score (LVZ) has not been investigated. The objective of the study was to assess associations between fecal markers for intestinal inflammation and LVZ and whether these associations were influenced by micronutrient adequacy among 9-24 months old children in Bhaktapur, Nepal. METHODS: Data was divided into 5 time slots (9-12, 12-15, 15-18, 18-21 and 21-24 months)...
April 3, 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29619129/sickle-cell-anemia-patients-in-use-of-hydroxyurea-association-between-polymorphisms-in-genes-encoding-metabolizing-drug-enzymes-and-laboratory-parameters
#6
Sètondji Cocou Modeste Alexandre Yahouédéhou, Magda Oliveira Seixas Carvalho, Rodrigo Mota Oliveira, Rayra Pereira Santiago, Caroline Conceição da Guarda, Suellen Pinheiro Carvalho, Júnia Raquel Dutra Ferreira, Milena Magalhães Aleluia, Elisângela Vitória Adorno, Marilda de Souza Gonçalves
This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+ ). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU- patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients ( p < 0...
2018: Disease Markers
https://www.readbyqxmd.com/read/29618937/the-impact-of-alpha-1-antitrypsin-augmentation-therapy-on-neutrophil-driven-respiratory-disease-in-deficient-individuals
#7
REVIEW
Danielle M Dunlea, Laura T Fee, Thomas McEnery, Noel G McElvaney, Emer P Reeves
Alpha-1 antitrypsin (AAT) is the most abundant serine protease inhibitor circulating in the blood. AAT deficiency (AATD) is an autosomal codominant condition affecting an estimated 3.4 million individuals worldwide. The clinical disease associated with AATD can present in a number of ways including COPD, liver disease, panniculitis and antineutrophil cytoplasmic antibody vasculitis. AATD is the only proven genetic risk factor for the development of COPD, and deficient individuals who smoke are disposed to more aggressive disease...
2018: Journal of Inflammation Research
https://www.readbyqxmd.com/read/29616482/impact-of-a-health-management-program-on-healthcare-outcomes-among-patients-on-augmentation-therapy-for-alpha-1-antitrypsin-deficiency-an-insurance-claims-analysis
#8
Michael A Campos, Michael C Runken, Angela M Davis, Michael P Johnson, Glenda A Stone, Ami R Buikema
INTRODUCTION: Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct® ; PD). OBJECTIVES: This study compared clinical and economic outcomes between patients with and without PD program participation...
April 3, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29615836/long-term-evolution-of-lung-function-in-individuals-with-alpha-1-antitrypsin-deficiency-from-the-spanish-registry-redaat
#9
Cristina Esquinas, Sonia Serreri, Miriam Barrecheguren, Esther Rodriguez, Alexa Nuñez, Francisco Casas-Maldonado, Ignacio Blanco, Pietro Pirina, Beatriz Lara, Marc Miravitlles
Background: The clinical course of alpha-1 antitrypsin deficiency (AATD) is very heterogeneous. It is estimated that 60% of individuals with severe AATD (Pi*ZZ) develop emphysema. The main objective of this study was to describe the outcomes of long-term lung function in individuals with AATD-associated emphysema after at least 8 years of follow-up. Materials and methods: We performed a retrospective analysis of longitudinal follow-up data of AATD PiZZ patients from the Spanish registry (AATD Spanish Registry [REDAAT])...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29611101/the-compensatory-immune-regulatory-reflex-system-cirs-in-depression-and-bipolar-disorder
#10
REVIEW
Michael Maes, Andre F Carvalho
Here, we review a novel concept namely the compensatory immune-regulatory reflex system (CIRS) as applied to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). There is evidence that a substantial subset of individuals with MDD and BD exhibit an activation of the immune-inflammatory response system (IRS), as indicated by an increased production of macrophagic M1 and T helper (Th)-1 pro-inflammatory cytokines, interleukin (IL)-6 trans-signaling, positive acute phase proteins (APPs), and complement factors...
April 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29607607/alpha-1-antitrypsin-in-cell-and-organ-transplantation
#11
Mel Berger, Mingyao Liu, Marc E Uknis, Maria Koulmanda
Limited availability of donor organs and risk of ischemia-reperfusion injury (IRI) seriously restrict organ transplantation. Therapeutics that can prevent or reduce IRI could potentially increase the number of transplants by increasing use of borderline organs and decreasing discards. Alpha-1 antitrypsin (AAT) is an acute phase reactant and serine protease inhibitor which limits inflammatory tissue damage. Purified plasma-derived AAT has been well-tolerated in more than 30 years of use to prevent emphysema in AAT deficient individuals...
April 1, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29603653/an-analytical-method-for-assessing-optimal-storage-conditions-of-gingival-crevicular-fluid-and-disclosing-a-peptide-biomarker-signature-of-gingivitis-by-maldi-tof-ms
#12
Mariaimmacolata Preianò, Giuseppina Maggisano, Maria Stella Murfuni, Chiara Villella, Corrado Pelaia, Tiziana Montalcini, Nicola Lombardo, Girolamo Pelaia, Rocco Savino, Rosa Terracciano
PURPOSE: Gingival crevicular fluid (GCF) is an important diagnostic source of biomarkers for both periodontitis and gingivitis. However, GCF peptide signature may change depending by factors such as handling and storage. Here we propose a standardized methodology for GCF analysis by MALDI-TOF/TOF-MS in order to distinguish a characteristic peptide signature of gingivitis. EXPERIMENTAL DESIGN: We determined the best storage/handling conditions which may ensure the stability of the endogenous peptidome in GCF and then we performed MALDI-TOF MS comparative analysis...
March 30, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29597895/in-vivo-genome-editing-partially-restores-alpha1-antitrypsin-in-a-murine-model-of-aat-deficiency
#13
Chun-Qing Song, Dan Wang, Tingting Jiang, Kevin O'Connor, Qiushi Tang, Lingling Cai, Xiangrui Li, Zhiping Weng, Hao Yin, Guangping Gao, Christian Mueller, Terence R Flotte, Wen Xue
CRISPR genome editing holds promise in the treatment of genetic diseases that currently lack effective long-term therapies. Patients with Alpha-1 Antitrypsin (AAT) deficiency develop progressive lung disease due to the loss of AAT's antiprotease function and liver disease due to a toxic gain of function of the common mutant allele. However, it remains unknown whether CRISPR-mediated AAT correction in the liver, where AAT is primarily expressed, can correct either or both defects. Here we show that AAV delivery of CRISPR can effectively correct Z-AAT mutation in the liver of a transgenic mouse model...
March 29, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29596184/chapter-6-3-studies-on-hepatic-metabolic-disorders-driven-by-espghan-members-the-case-of-alpha1-antitrypsin-deficiency-cystic-fibrosis-and-urea-cycle-defects
#14
Giulia Paolella, Giovanna Alfano, Pietro Vajro
No abstract text is available yet for this article.
April 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29592975/fulminant-hepatic-failure-in-the-setting-of-progressive-anca-associated-vasculitis-associated-with-a-rare-alpha-1-antitrypsin-phenotype-piee
#15
Ronald Reilkoff, Laurel Stephenson
Abnormalities in alpha-1 antitrypsin (AAT) proteins are risk factors for human disease. While the most common is AAT deficiency, a genetic disorder associated with chronic obstructive pulmonary disease, additional disorders associated with AAT abnormalities are increasingly recognised. We describe a middle-aged woman who presented with fulminant hepatic and multiorgan failure. Evaluation revealed the patient to have a rare AAT phenotype PiEE. Her clinical presentation was consistent with antineutrophilic cytoplasmic antibody-associated vasculitis, and her history suggested features of panniculitis...
March 28, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29588497/targeted-in-vivo-knock-in-of-human-alpha-1-antitrypsin-cdna-using-adenoviral-delivery-of-crispr-cas9
#16
Calvin J Stephens, Elena Kashentseva, William Everett, Lyudmila Kaliberova, David T Curiel
Serum deficiency diseases such as alpha-1-antitrypsin deficiency are characterized by reduced function of serum proteins, caused by deleterious genetic mutations. These diseases are promising targets for genetic interventions. Gene therapies using viral vectors have been used to introduce correct copies of the disease-causing gene in preclinical and clinical studies. However, these studies highlighted that disease-alleviating gene expression is lost over time. Integration into a specific chromosomal site could provide lasting therapeutic expression to overcome this major limitation...
March 27, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29573789/alpha-1-antitrypsin-inhibits-microglia-activation-and-facilitates-the-survival-of-ipsc-grafts-in-hypertension-mouse-model
#17
Sijing Yang, Bikun Xian, Kaijing Li, Ziming Luo, Yuchun Liu, Dongpeng Hu, Jian Ge
This study was conducted to investigate the use of Alpha 1-antitrypsin (AAT) to inhibit microglia activation in chronic hypertension model and provide a permissive environment for stem cell transplantation. Chronic ocular hypertension of C57BL/6 mice using magnetic microbead injection was induced 3 weeks prior to iPSCs transplantation. The ocular hypertension model was assessed histologically and intraocular pressure was measured. Survival of grafted cells and microglia activation were examined by flow cytometry and immunofluorescence in AAT and PBS treated hosts...
March 16, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29573137/heterozygosity-for-the-alpha-1-antitrypsin-z-allele-in-cirrhosis-is-associated-with-more-advanced-disease
#18
Benedikt Schaefer, Mattias Mandorfer, André Viveiros, Armin Finkenstedt, Peter Ferenci, Stefan Schneeberger, Herbert Tilg, Heinz Zoller
Alpha-1-antitrypsin deficiency (A1ATD) due to homozygosity for the Z-allele (ZZ) is an established risk factor for cirrhosis, but the liver disease risk in heterozygous Z-allele carriers (MZ) is controversial. The aim of the present study was to determine the prevalence of the MZ genotype among patients with cirrhosis and the associated risk of decompensation and liver transplantation/mortality. An unselected cohort of 561 patients with cirrhosis and 248 deceased liver donors were genotyped for the A1ATD risk alleles Z and S using a validated allelic discrimination assay...
March 23, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29572094/hepatic-targeted-rna-interference-provides-persistent-knockdown-of-alpha-1-antitrypsin-levels-in-zz-patients
#19
Alice M Turner, Jan Stolk, Robert Bals, Jason Lickliter, James Hamilton, Dawn R Christianson, Bruce D Given, Jonathan G Burdon, Rohit Loomba, James K Stoller, Jeffery H Teckman
BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder causing pulmonary and liver disease. The PiZ mutation results in mis-folded alpha-1 antitrypsin protein (Z-AAT) leading to hepatocyte accumulation, fibrosis and cirrhosis. RNAi-based therapeutics silencing production of hepatic Z-AAT might benefit patients with AATD-associated liver disease. This study evaluated an RNAi therapeutic to silence production of alpha-1 antitrypsin. METHODS: Part A of this double-blind first-in-human study randomized 54 healthy volunteers (HVs) into single dose cohorts (2 placebo: 4 active), receiving escalating doses of the investigational agent ARC-AAT from 0...
March 20, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29564590/proteomic-analysis-of-the-antidepressant-effects-of-shen-zhi-ling-in-depressed-patients-identification-of-proteins-associated-with-platelet-activation-and-lipid-metabolism
#20
Chao Chen, Yuan Hu, Xian-Zhe Dong, Xiao-Jiang Zhou, Li-Hua Mu, Ping Liu
Shen-Zhi-Ling (SZL) is a Chinese medicine formulated from a Kai-Xin-San decoction that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. However, the underlying mechanisms remain unclear. We investigated biological changes in depression patients (DPs) exhibiting antidepressant responses to SZL treatment using proteomic techniques. We performed label-free quantitative proteomic analysis and liquid chromatography-tandem mass spectrometry to discover and examine altered proteins involved in depression and antidepressant treatment...
March 21, 2018: Cellular and Molecular Neurobiology
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