2,654 results match your criteria Alpha1-Antitrypsin Deficiency


Rapid liver disease progression in a patient with homozygous alpha1-antitrypsin deficiency (Pi*ZZ genotype).

Liver Transpl 2018 Dec 7. Epub 2018 Dec 7.

Internal Medicine III, University Hospital Aachen, Germany.

With great interest, we read the study by Schaefer et. al. suggesting that the carriage of a heterozygous PiZ variant of alpha1-antitrypsin (AAT) predisposes to a faster development of decompensated liver disease [1]. Read More

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December 2018

Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.

Regen Ther 2018 Dec 24;9:45-57. Epub 2018 Aug 24.

Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.

Introduction: We previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/β-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/β-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs.

Methods: We manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2. Read More

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December 2018

Application of Lactoferrin and 1-Antitrypsin in Gingival Retention Fluid to Diagnosis of Periodontal Disease.

Dis Markers 2018 7;2018:4308291. Epub 2018 Nov 7.

Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan.

Objectives: Periodontal disease is prevalent and has an inflammation associated with not only oral but also systemic pathologies. The diagnosis by biomarkers is required for clinical practice on periodontal disease. The lactoferrin and 1-antitrypsin were both inflammation-related molecules. Read More

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November 2018

Conditions and Factors Associated With Spontaneous Coronary Artery Dissection (from a National Population-Based Cohort Study).

Am J Cardiol 2018 Oct 30. Epub 2018 Oct 30.

Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts. Electronic address:

The pathophysiology of spontaneous coronary artery dissection (SCAD) is heterogeneous, associated with systemic arteriopathies and inflammatory diseases, and often compounded by environmental precipitants, genetics, or stressors. However, the frequency of these associated conditions with SCAD on a population level remains unknown. Therefore, the objective of this analysis was to evaluate heterogeneous phenotypes of SCAD in the United States using data from the Nationwide Inpatient Sample collected from January 1, 2004, to September 31, 2015. Read More

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October 2018
1 Read
3.280 Impact Factor

Alpha1-Antitrypsin Deficiency: Transition of Care for the Child With AAT Deficiency into Adulthood.

Curr Pediatr Rev 2018 Nov 12. Epub 2018 Nov 12.

Division of Pediatric Gastroenterology, Hepatology and Nutrition MUSC Children's Hospital, South Carolina. United States.

IMPORTANCE Alpha1-antitrypsin (AAT) deficiency is a common, but underdiagnosed genetic condition, affecting 1 in 1500 individuals, which can present insidiously with liver disease in children. Although clinical practice guidelines exist for the management of AAT deficiency, especially with regards to pulmonary involvement, there are no published recommendations that specifically relate to the management of the liver disease and monitoring for lung disease associated with this condition, particularly in children. OBJECTIVE To review the literature on the management of AAT deficiency-associated liver disease in adults and children. Read More

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November 2018
4 Reads

Safety and pharmacokinetics of Alpha-1 MP (Prolastin-C) in Japanese patients with alpha-antitrypsin (AAT) deficiency.

Respir Investig 2018 Nov 8. Epub 2018 Nov 8.

Grifols Japan KK, Osaka, Japan.

Background: Alpha-Proteinase Inhibitor, Modified Process (Alpha-1 MP) is used for augmentation therapy in alpha1-antitrypsin deficiency (AATD), an extremely rare disease in Japan. Weekly doses of 60 mg/kg Alpha-1 MP have been shown to be safe and well tolerated in non-Japanese subjects, but the safety and pharmacokinetics (PK) have not been evaluated in Japanese subjects. The objectives of this study were to evaluate the safety and PK of 60 mg/kg Alpha-1 MP administered by weekly IV infusions over 8 weeks in Japanese subjects with AATD. Read More

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November 2018
2 Reads

Alpha 1 antitrypsin distribution in an allergic asthmatic population sensitized to house dust mites.

Clin Transl Allergy 2018 2;8:44. Epub 2018 Nov 2.

5Allergy Unit, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.

Background And Objective: Severe alpha1 antitrypsin deficiency has been clearly associated with pulmonary emphysema, but its relationship with bronchial asthma remains controversial. Some deficient alpha 1 antitrypsin (AAT) genotypes seem to be associated with asthma development. The objective of this study was to analyze the distribution of AAT genotypes in asthmatic patients allergic to house dust mites (HDM), and to asses a possible association between these genotypes and severe asthma. Read More

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November 2018
1 Read

HSP27, ALDH6A1 and Prohibitin Act as a Trio-biomarker to Predict Survival in Late Metastatic Prostate Cancer.

Anticancer Res 2018 Nov;38(11):6551-6560

Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea

Background/aim: The aim of this study was to evaluate the usefulness of biomarkers related to prostate cancer metastasis and survival of patients.

Materials And Methods: Proteomics were used for detecting significant differences in protein expression among normal prostate, localized prostate cancer and metastatic cancer using 2-dimensional gel electrophoresis and mass spectrometry. mRNA expression was then examined in order to further confirm significant differences in protein expression. Read More

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November 2018
7 Reads

Geographical Distribution of COPD Prevalence in the Americas.

COPD 2018 Oct 30:1-9. Epub 2018 Oct 30.

f Pneumology Department , Hospital Universitari Vall d'Hebron , Barcelona , Spain.

Surveys estimating chronic obstructive pulmonary disease (COPD) prevalence are unevenly distributed in the Americas, which make it difficult to estimate accurately its geographical distribution. The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, even when real data are few or widely spread. We aimed to represent cartographically the COPD prevalence in the Americas by means of a blue to red scale representation of the prevalence data, where different values are represented as different colours, and a population density filtered IDW interpolation mapping, where areas with a population density <0. Read More

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October 2018
5 Reads

Author Correction: α1-Antitrypsin deficiency.

Nat Rev Dis Primers 2018 Oct 29;4(1):40. Epub 2018 Oct 29.

Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.

In Figure 6 of this article (PDF and HTML) the arrows labelled 'Depolymerization' and 'Polymerization' should be labelled 'Polymerization' and 'Depolymerization', respectively. Read More

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October 2018
1 Read

Characterization of residue-specific glutathionylation of CSF proteins in multiple sclerosis - A MS-based approach.

Anal Biochem 2019 Jan 24;564-565:108-115. Epub 2018 Oct 24.

Division of Molecular Medicine, Clinical Proteomics Unit, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, 560034, India. Electronic address:

Reduction of a disulfide linkage between cysteine residues in proteins, a standard step in the preanalytical preparation of samples in conventional proteomics approach, presents a challenge to characterize S-glutathionylation of proteins. S-glutathionylation of proteins has been reported in medical conditions associated with high oxidative stress. In the present study, we attempted to characterize glutathionylation of CSF proteins in patients with multiple sclerosis which is associated with high oxidative stress. Read More

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January 2019
6 Reads
2.220 Impact Factor

Alpha1-Antitrypsin Deficiency as an Incidental Finding in Clinical Genetic Testing.

Am J Respir Crit Care Med 2018 Oct 25. Epub 2018 Oct 25.

Brigham and Women's Hospital, Medicine, Boston, Massachusetts, United States.

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October 2018
1 Read

Oxidation-resistant and thermostable forms of alpha-1 antitrypsin from inclusion bodies.

FEBS Open Bio 2018 Oct 17;8(10):1711-1721. Epub 2018 Sep 17.

Key Laboratory for Microorganisms and Biotransformation College of Life Science South-Central University for Nationalities Wuhan China.

Native α1-antitrypsin (AAT) is a 52-kDa glycoprotein that acts as an antiprotease and is the physiological inhibitor of neutrophil serine proteases. The main function of AAT is to protect the lung from proteolytic damage induced by inflammation. AAT deficiency (AATD) is a codominant autosomal disorder caused by pathogenic mutations in SERPINA1 gene, leading to reduced levels of serum AAT. Read More

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October 2018
5 Reads

Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa.

Clin Invest Med 2018 Sep 30;41(3):E136-E143. Epub 2018 Sep 30.

Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology.

Introduction: CF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy. Read More

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September 2018
1 Read

Expression, Purification, and Characterization of Recombinant Human α-Antitrypsin Produced Using Silkworm-Baculovirus Expression System.

Mol Biotechnol 2018 Dec;60(12):924-934

Laboratory of Insect Genome Science, Kyushu University Graduate School of Bioresource and Bioenvironmental Science, Hakozaki 6-10-1, Higashi-ku, Fukuoka, 812-8581, Japan.

Human α-antitrypsin (AAT) is the most abundant serine proteinase inhibitor (serpin) in the human plasma. Commercially available AAT for the medications of deficiency of α-antitrypsin is mainly purified from human plasma. There is a high demand for a stable and low-cost supply of recombinant AAT (rAAT). Read More

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December 2018
2 Reads

α1-antitrypsin mitigates NLRP3-inflammasome activation in amyloid β-stimulated murine astrocytes.

J Neuroinflammation 2018 Sep 27;15(1):282. Epub 2018 Sep 27.

Department of Neurology, RWTH Aachen University, Aachen, Germany.

Background: Neuroinflammation has an essential impact on the pathogenesis and progression of Alzheimer's disease (AD). Mostly mediated by microglia and astrocytes, inflammatory processes lead to degeneration of neuronal cells. The NLRP3-inflammasome (NOD-like receptor family, pyrin domain containing 3) is a key component of the innate immune system and its activation results in secretion of the proinflammatory effectors interleukin-1β (IL-1β) and interleukin-18 (IL-18). Read More

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September 2018
1 Read

Silence of α1-Antitrypsin Inhibits Migration and Proliferation of Triple Negative Breast Cancer Cells.

Med Sci Monit 2018 Sep 27;24:6851-6860. Epub 2018 Sep 27.

Department of Thyroid-Breast Surgery, The Second Affiliate Hospital of Kunming Medical University, Kunming, Yunnan, China (mainland).

BACKGROUND α1-antitrypsin (α1-AT) is highly expressed in many tumors. However, to the best of our knowledge, its relationship to triple negative breast cancer (TNBC) has not yet been studied. Thus, in this research we first explored the influence of α1-AT silencing on the abilities of migration and invasion, and then further study its molecular mechanism in TNBC cells. Read More

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September 2018

Safety of biweekly α-antitrypsin treatment in the RAPID programme.

Eur Respir J 2018 Nov 29;52(5). Epub 2018 Nov 29.

Irish Centre for Genetic Lung disease, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.

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November 2018

Lung volume reduction surgery beyond the NETT selection criteria.

J Thorac Dis 2018 Aug;10(Suppl 23):S2748-S2753

Department of Thoracic Surgery, University Hospital Zurich, Switzerland.

Lung volume reduction surgery (LVRS) for symptomatic patients with advanced emphysema was proven to be successful in a large randomized multi-center trial (NETT) and in several smaller randomized single center trials. This evidence primarily concerns patients with heterogeneous, upper-lobe predominant emphysema and low exercise tolerance within certain selection criteria regarding lung function values. As the most important effect of LVRS is generated by reducing the hyperinflation, even patients with homogeneous emphysema morphology profit from the procedure. Read More

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August 2018
2 Reads

Acute-phase response and its biomarkers in acute and chronic urticaria.

Postepy Dermatol Alergol 2018 Aug 21;35(4):400-407. Epub 2018 Aug 21.

Department of Dermatology, Poznan University of Medical Sciences, Poznan, Poland.

Introduction: Since urticaria is a persisting inflammatory disease it is important to establish the prognostic factors for the duration and severity of the disease.

Aim: To evaluate serum concentrations of selected acute-phase proteins (APP) in patients with various forms of urticaria as compared to healthy volunteers and also to analyze these concentrations in different types of urticaria. Additionally, to evaluate the correlation between serum levels of selected APP and disease activity. Read More

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August 2018
8 Reads

Update on α-antitrypsin deficiency.

Breathe (Sheff) 2018 Jun;14(2):e17-e24

Center for Diagnosis of Inherited Alpha1-antitrypsin Deficiency, Dept of Internal Medicine and Therapeutics, Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy.

α-Antitrypsin deficiency (AATD) is an inherited metabolic disorder in which mutations in the coding sequence of the gene prevent secretion of α-antitrypsin (α-AT) and cause predisposition to pulmonary and liver diseases. The heterogeneity of clinical manifestations in AATD is related to the complexity of biological function of α-AT. The role of smoking is crucial in the natural history of lung damage progression in severe AATD individuals, even if it also partly explains the heterogeneity in lung disease. Read More

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June 2018
5 Reads

Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases.

FASEB J 2018 Aug 21:fj201800752R. Epub 2018 Aug 21.

Department of Medicine 3, Friedrich Alexander University of Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.

Papillon-Lefèvre syndrome (PLS) is characterized by nonfunctional neutrophil serine proteases (NSPs) and fulminant periodontal inflammation of unknown cause. Here we investigated neutrophil extracellular trap (NET)-associated aggregation and cytokine/chemokine-release/degradation by normal and NSP-deficient human and mouse granulocytes. Stimulated with solid or soluble NET inducers, normal neutrophils formed aggregates and both released and degraded cytokines/chemokines. Read More

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August 2018
1 Read
5.040 Impact Factor

Measuring the effects of α -antitrypsin polymerisation on the structure and biophysical properties of the endoplasmic reticulum.

Biol Cell 2018 Nov 10;110(11):249-255. Epub 2018 Sep 10.

Cambridge Institute for Medical Research (CIMR), University of Cambridge, Wellcome Trust/MRC Building, Cambridge, CB2 0XY, UK.

An important function of the endoplasmic reticulum (ER) is to serve as a site of secretory protein folding. When the accumulation of misfolded proteins threatens to disturb luminal homoeostasis, the cell is said to experience ER stress. By contrast, the accumulation of well-folded proteins inside the ER leads to a distinct form of strain called ER overload. Read More

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November 2018
1 Read

Liver disease in adults with α1-antitrypsin deficiency.

United European Gastroenterol J 2018 Jun 28;6(5):710-718. Epub 2018 Feb 28.

Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background: The natural history of adult liver disease due to α1-antitrypsin deficiency (A1AD) remains poorly understood.

Objective: We investigated whether heterozygosity for the Z-allele predisposes for the development of clinically significant portal hypertension (CSPH). Moreover, we aimed to non-invasively assess the prevalence of liver fibrosis and hepatic steatosis in adults with A1AD treated by pulmonologists. Read More

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June 2018
6 Reads

ER-to-lysosome-associated degradation of proteasome-resistant ATZ polymers occurs via receptor-mediated vesicular transport.

EMBO J 2018 Sep 3;37(17). Epub 2018 Aug 3.

Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland

Maintenance of cellular proteostasis relies on efficient clearance of defective gene products. For misfolded secretory proteins, this involves dislocation from the endoplasmic reticulum (ER) into the cytosol followed by proteasomal degradation. However, polypeptide aggregation prevents cytosolic dislocation and instead activates ill-defined lysosomal catabolic pathways. Read More

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September 2018
15 Reads

Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis.

Gut 2018 Aug 1. Epub 2018 Aug 1.

Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.

Objective: Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants ('Pi*Z' and 'Pi*S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse.

Design: We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Read More

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August 2018
12 Reads

NorUDCA promotes degradation of α1-antitrypsin mutant Z protein by inducing autophagy through AMPK/ULK1 pathway.

PLoS One 2018 1;13(8):e0200897. Epub 2018 Aug 1.

Pediatrics and Biochemistry, Saint Louis University, and Cardinal Glennon Children's Medical Center, St. Louis, Missouri, United States of America.

Alpha-1 Antitrypsin (α1AT) Deficiency is a genetic disease in which accumulation of α1AT mutant Z (α1ATZ) protein in the ER of hepatocytes causes chronic liver injury, liver fibrosis, and hepatocellular carcinoma. No effective medical therapy is currently available for the disease. We previously found that norUDCA improves the α1AT deficiency associated liver disease by promoting autophagic degradation of α1ATZ protein in liver in a mouse model of the disease. Read More

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August 2018
2 Reads

Correction to: Genetically engineered cell lines for α1-antitrypsin expression.

Biotechnol Lett 2018 10;40(9-10):1439

School of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China.

In the original publication of the article, the Acknowledgement section was published incompletely. The complete Acknowledgement is given in this Correction. Read More

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October 2018
1 Read

EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.

J Biol Chem 2018 Sep 18;293(36):13932-13945. Epub 2018 Jul 18.

From the Department of Biochemistry and Molecular Biology and

Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize -linked glycans on misfolded proteins through its mannosidase-like domain (MLD). However, recent studies have demonstrated that EDEM1 binds to some misfolded proteins in a glycan-independent manner, suggesting a more complex binding landscape for EDEM1. In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys), required for binding under stringent detergent conditions. Read More

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September 2018
1 Read

The sinister face of heme oxygenase-1 in brain aging and disease.

Prog Neurobiol 2018 Jul 28. Epub 2018 Jul 28.

Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery McGill University, Montreal, Quebec, Canada.

Under stressful conditions, cellular heme catabolism to carbon monoxide, iron and biliverdin is mediated by the 32 kDa enzyme, heme oxygenase-1 (HO-1). A wide range of pro-oxidant and inflammatory stimuli act on diverse consensus sequences within the Hmox1 promoter to rapidly induce the gene. There is ample evidence attesting to the beneficial effects of HO-1 upregulation in brain. Read More

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July 2018
36 Reads

Advances in managing COPD related to α -antitrypsin deficiency: An under-recognized genetic disorder.

Allergy 2018 Nov 26;73(11):2110-2121. Epub 2018 Jul 26.

Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.

α -Antitrypsin deficiency (AATD) predisposes individuals to chronic obstructive pulmonary disease (COPD) and liver disease. Despite being commonly described as rare, AATD is under-recognized, with less than 10% of cases identified. The following is a comprehensive review of AATD, primarily for physicians who treat COPD or asthma, covering the genetics, epidemiology, clinical presentation, screening and diagnosis, and treatments of AATD. Read More

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November 2018
2 Reads

Intestinal Inflammation in Chilean Infants Fed With Bovine Formula vs. Breast Milk and Its Association With Their Gut Microbiota.

Front Cell Infect Microbiol 2018 21;8:190. Epub 2018 Jun 21.

Departamento de Pediatría y Cirugía Infantil, Facultad de Medicina, Hospital Dr. Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile.

Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. Read More

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June 2018
7 Reads

Alpha1 antitrypsin deficiency due to an homozygous PI* Null Q0Cairo mutation: Early onset of pulmonary manifestations and variability of clinical expression.

Respir Med Case Rep 2018 10;24:58-62. Epub 2018 Apr 10.

CHU Lille, Service de Biochimie et Biologie Moléculaire Hormonologie, Métabolisme-Nutrition, Oncologie, F-59000 Lille, France.

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the gene. This genetic disorder is mainly associated with development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here we report a very rare alpha-1 antitrypsin Null Q0cairo homozygous mutation characterized by a complete absence of alpha-1 antitrypsin in the plasma, in a non-consanguineous Moroccan family. Read More

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April 2018
4 Reads

Testing for alpha-1 antitrypsin in COPD in outpatient respiratory clinics in Spain: A multilevel, cross-sectional analysis of the EPOCONSUL study.

PLoS One 2018 28;13(6):e0198777. Epub 2018 Jun 28.

Pulmonary Department, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España.

Background: Alpha-1 antitrypsin deficiency (AATD) is the most common hereditary disorder in adults, but is under-recognized. In Spain, the number of patients diagnosed with AATD is much lower than expected according to epidemiologic studies. The objectives of this study were to assess the frequency and determinants of testing serum α1-antitrypsin (AAT) levels in COPD patients, and to describe factors associated with testing. Read More

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June 2018
13 Reads

Hermansky-Pudlak syndrome with a novel genetic variant in and subsequent accelerated pulmonary fibrosis: significance for phenocopy diseases.

Thorax 2018 Nov 25;73(11):1085-1088. Epub 2018 Jun 25.

Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the gene. Read More

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November 2018
16 Reads

Similarities in the Computed Tomography Appearance in α1-Antitrypsin Deficiency and Smoking-Related Chronic Obstructive Pulmonary Disease in a Smoking Collective.

Respiration 2018 25;96(3):231-239. Epub 2018 Jun 25.

Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany.

Background: Emphysematous destruction of lung parenchyma visible in computed tomography (CT) can be attributed to chronic obstructive pulmonary disease (COPD) or to α1-antitrypsin deficiency (AATD).

Objectives: We evaluated if visual semiquantitative phenotyping of CT data helps identifying individuals with AATD in a group of smokers with severe emphysema and airflow limitation.

Method: n = 14 patients with AATD and n = 15 with COPD and a minimum of 10 pack years underwent CT, clinical assessment, and full-body plethysmography. Read More

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June 2018
6 Reads

Reduced Susceptibility to VIRIP-Based HIV-1 Entry Inhibitors Has a High Genetic Barrier and Severe Fitness Costs.

J Virol 2018 09 16;92(17). Epub 2018 Aug 16.

Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany

VIRIP has been identified as natural HIV-1 inhibitor targeting the gp41 fusion peptide. An optimized analogue (VIR-576) was effective in a phase I/II clinical trial and initial studies showed that HIV-1 resistance to VIRIP-based inhibitors has a high genetic barrier. Partially resistant CXCR4 (X4)-tropic HIV-1 NL4-3 variants could be obtained, however, after more than 15 months of passaging in MT-4 cells in the presence of another derivative (VIR-353). Read More

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September 2018
9 Reads

Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients.

Front Pharmacol 2018 5;9:545. Epub 2018 Jun 5.

INSERM, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France.

Cystic fibrosis (CF) is characterized by a chronic pulmonary inflammation. In CF, glucocorticoids (GC) are widely used, but their efficacy and benefit/risk ratio are still debated. In plasma, corticosteroid-binding globulin (CBG) binds 90% of GC and delivers them to the inflammatory site. Read More

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June 2018
11 Reads

Diagnosis of alpha1-antitrypsin deficiency not just in severe COPD.

Pulmonology 2018 Jun 18. Epub 2018 Jun 18.

Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Electronic address:

Alpha1-antitrypsin deficiency (AATD) is a well known genetic risk factor for pulmonary disease and is the most frequent hereditary disease diagnosed in adults. Despite being one of the most common hereditary diseases, AATD remains under-diagnosed because of its variable clinical presentation and the poor knowledge of this disease by physicians. With the aim of identifying clinical differences that could influence early diagnosis, we compared two groups of six AATD Pi*ZZ patients with different lung function severity and clinical expression at diagnosis. Read More

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June 2018
2 Reads

Differentiation of umbilical cord mesenchymal stem cells into hepatocytes in comparison with bone marrow mesenchymal stem cells.

Mol Med Rep 2018 Aug 18;18(2):2009-2016. Epub 2018 Jun 18.

Department of Hepatobiliary Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

Mesenchymal stem cells (MSCs) are considered to be an ideal source for the cell therapy of end‑stage liver diseases. Umbilical cord (UC)‑MSCs can be obtained via a non‑invasive procedure and can be easily cultured, making them potentially superior candidates for cell transplantation when compared with MSCs from other sources. In the present study, UC‑MSCs were induced to differentiate into hepatocytes and were compared with bone marrow (BM)‑MSCs for their hepatic differentiation potential. Read More

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August 2018
8 Reads

Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases: a prospective study exploring the 'common soil' hypothesis.

Cardiovasc Diabetol 2018 06 12;17(1):87. Epub 2018 Jun 12.

Department of Clinical Sciences, Lund University, CRC 60:13, Jan Waldenströms gata 35, 20502, Malmö, Sweden.

Background: Chronic low-grade inflammation and associated insulin resistance and metabolic abnormalities have been proposed as 'common soil' for diabetes mellitus (DM) and cardiovascular disease (CVD). This paper aimed to investigate the inflammatory profiles of DM and CVD and to distinguish their shared and specific markers.

Methods: Based on the Malmö Diet and Cancer cohort, total and differential leukocyte counts were measured in 25,969 participants without previous DM or CVD and were studied in relation to incident DM (mean follow-up 17. Read More

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June 2018
4 Reads

Innate Immune System Status of Sulphur Mustard-Poisoned Iranian Veterans Three Decades after Exposure.

Basic Clin Pharmacol Toxicol 2018 Nov 8;123(5):635-639. Epub 2018 Aug 8.

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Sulphur mustard (SM) is an incapacitating chemical warfare agent which causes acute and chronic toxicities in different body organs of affected individuals. The aim of this study was to investigate the innate immune status of the Iranian veterans who were exposed to SM around 30 years earlier and had more than 25% disabilities. In this regard, most functional and non-functional parameters of innate immunity were evaluated in 35 veterans. Read More

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November 2018
17 Reads

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis.

Joint Bone Spine 2018 Jun 6. Epub 2018 Jun 6.

EA 7408, University Grenoble Alpes, GREPI, 38400 Saint-Martin-d'Hères, France; Rheumatology Department, centre hospitalier universitaire Grenoble Alpes, hôpital Sud Echirolles, 38130 Echirolles, France.

Objectives: Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. Read More

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June 2018
9 Reads

Enhancement of Recombinant Protein Production in Transgenic Plant Cell Suspension Cultures with Co-Cultivation of Containing Silencing Suppressors.

Int J Mol Sci 2018 May 24;19(6). Epub 2018 May 24.

Department of Chemical Engineering and Materials Science, University of California, 1 Shields Avenue, Davis, CA 95616, USA.

We have previously demonstrated that the inducible plant viral vector (CMViva) in transgenic plant cell cultures can significantly improve the productivity of extracellular functional recombinant human alpha-1-antiryspin (rAAT) compared with either a common plant constitutive promoter ( (CaMV) 35S) or a chemically inducible promoter (estrogen receptor-based XVE) system. For a transgenic plant host system, however, viral or transgene-induced post-transcriptional gene silencing (PTGS) has been identified as a host response mechanism that may dramatically reduce the expression of a foreign gene. Previous studies have suggested that viral gene silencing suppressors encoded by a virus can block or interfere with the pathways of transgene-induced PTGS in plant cells. Read More

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May 2018
2 Reads

hiPSC hepatocyte model demonstrates the role of unfolded protein response and inflammatory networks in α-antitrypsin deficiency.

J Hepatol 2018 Oct 5;69(4):851-860. Epub 2018 Jun 5.

Wellcome Trust and MRC Cambridge Stem Cell Institute, Department of Surgery, University of Cambridge, UK; Wellcome Trust Sanger Institute, Genome Campus Hinxton, UK. Electronic address:

Background & Aims: α-Antitrypsin deficiency (A1ATD) is an autosomal recessive disorder caused by mutations in the SERPINA1 gene. Individuals with the Z variant (Gly342Lys) retain polymerised protein in the endoplasmic reticulum (ER) of their hepatocytes, predisposing them to liver disease. The concomitant lack of circulating A1AT also causes lung emphysema. Read More

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October 2018
35 Reads

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.

Sci Transl Med 2018 Jun;10(444)

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3026, USA.

Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis. Read More

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June 2018
10 Reads
15.840 Impact Factor

Trends of testing for and diagnosis of α-antitrypsin deficiency in the UK: more testing is needed.

Eur Respir J 2018 Jul 4;52(1). Epub 2018 Jul 4.

Dept of Respiratory Medicine, Cambridge NIHR BRC, Addenbrookes Hospital, Cambridge, UK.

α-antitrypsin deficiency (AATD) significantly increases the risk of developing chronic obstructive pulmonary disease (COPD), and testing of all COPD patients for AATD is recommended by the World Health Organization, European Respiratory Society and Global Initiative for Chronic Obstructive Lung Disease (GOLD). We aimed to determine trends for testing and diagnosing AATD from 1990 to 2014.This study analysed all patients diagnosed with COPD from about 550 UK Optimum Patient Care Research Database general practices, including a subgroup of those diagnosed before the age of 60 years. Read More

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July 2018
6 Reads

An Enzyme Immunoassay for Determining Immunoreactive Trypsinogen (IRT) in Dried Blood Spots on Filter Paper Using an Ultra-Microanalytical System.

Appl Biochem Biotechnol 2018 Dec 29;186(4):1034-1046. Epub 2018 May 29.

Center of Immunoassay, 134th Street and 25th Avenue, Cubanacán, Playa, 6653, Havana, Cuba.

Cystic fibrosis (CF) is a severe autosomal recessive disorder. It is caused by mutations in the CF transmembrane conductance regulator gene. Early diagnosis of CF can be carried out by determining high immunoreactive trypsinogen (IRT) blood values in newborns. Read More

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December 2018
11 Reads

SERPINA1 Hepatocyte-Specific Promoter Polymorphism Associate with Chronic Obstructive Pulmonary Disease in a Study of Kashmiri Ancestry Individuals.

Lung 2018 Aug 26;196(4):447-454. Epub 2018 May 26.

Department of Biotechnology, University of Kashmir, Srinagar, J&K, 190006, India.

Purpose: Different mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, - 10T/C mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of - 10C genotype that is associated with decreased levels of serum alpha1-antitrypsin (α1AT) in COPD patients. Read More

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August 2018
4 Reads
2.171 Impact Factor