alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.alpha 1-Antitrypsin Deficiency: Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.Pulmonary Emphysema: Enlargement of air spaces distal to the TERMINAL BRONCHIOLES where gas-exchange normally takes place. This is usually due to destruction of the alveolar wall. Pulmonary emphysema can be classified by the location and distribution of the lesions.Pancreatic Elastase: A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 3.4.21.36.alpha 1-Antichymotrypsin: Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity in vitro. The protein also has a role as an acute-phase protein and is active in the control of immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily.Emphysema: A pathological accumulation of air in tissues or organs.Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.Leukocyte Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.alpha7 Nicotinic Acetylcholine Receptor: A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Integrin alpha3beta1: Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.Integrin alpha4: An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Integrin alpha5beta1: An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.OrosomucoidProtein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Integrin alpha4beta1: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.Interleukin-1alpha: An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Liver Diseases: Pathological processes of the LIVER.Kinetics: The rate dynamics in chemical or physical systems.Integrin alpha2beta1: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Hepatocyte Nuclear Factor 1-alpha: Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Haptoglobins: Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Integrin alpha5: This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.Integrin alpha1beta1: Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.Integrin alpha6beta1: A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.Protein-Losing Enteropathies: Pathological conditions in the INTESTINES that are characterized by the gastrointestinal loss of serum proteins, including SERUM ALBUMIN; IMMUNOGLOBULINS; and at times LYMPHOCYTES. Severe condition can result in HYPOGAMMAGLOBULINEMIA or LYMPHOPENIA. Protein-losing enteropathies are associated with a number of diseases including INTESTINAL LYMPHANGIECTASIS; WHIPPLE'S DISEASE; and NEOPLASMS of the SMALL INTESTINE.Macroglobulins: Serum globulins with high molecular weight. (Dorland, 28th ed)Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Integrin alpha6beta4: This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.Integrin alpha Chains: The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.Albumins: Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Integrin alpha1: An integrin alpha subunit that binds COLLAGEN and LAMININ though its I domain. It combines with INTEGRIN BETA1 to form the heterodimer INTEGRIN ALPHA1BETA1.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).alpha-Macroglobulins: Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Homozygote: An individual in which both alleles at a given locus are identical.Alpha Rhythm: Brain waves characterized by a relatively high voltage or amplitude and a frequency of 8-13 Hz. They constitute the majority of waves recorded by EEG registering the activity of the parietal and occipital lobes when the individual is awake, but relaxed with the eyes closed.Protein C Inhibitor: A member of the serpin family of proteins that is found in plasma and urine. It is dependent on heparin and is able to inhibit activated PROTEIN C; THROMBIN; KALLIKREIN; and other SERINE ENDOPEPTIDASES.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Proprotein Convertase 5: A serine endopeptidase found primarily in the EXTRACELLULAR MATRIX. It has specificity for cleavage of a variety of substrates including PRORENIN, pro-membrane type-1 matrix metalloproteinase, and NEURAL CELL ADHESION MOLECULE L1.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Pancreatin: A mammalian pancreatic extract composed of enzymes with protease, amylase and lipase activities. It is used as a digestant in pancreatic malfunction.Integrin alpha3: An integrin alpha subunit that occurs as alternatively spliced isoforms. The isoforms are differentially expressed in specific cell types and at specific developmental stages. Integrin alpha3 combines with INTEGRIN BETA1 to form INTEGRIN ALPHA3BETA1 which is a heterodimer found primarily in epithelial cells.Furin: A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Mice, Inbred C57BL
The disulfide-bonded loop of chromogranin B mediates membrane binding and directs sorting from the trans-Golgi network to secretory granules. (1/1525)
The disulfide-bonded loop of chromogranin B (CgB), a regulated secretory protein with widespread distribution in neuroendocrine cells, is known to be essential for the sorting of CgB from the trans-Golgi network (TGN) to immature secretory granules. Here we show that this loop, when fused to the constitutively secreted protein alpha1-antitrypsin (AT), is sufficient to direct the fusion protein to secretory granules. Importantly, the sorting efficiency of the AT reporter protein bearing two loops (E2/3-AT-E2/3) is much higher compared with that of AT with a single disulfide-bonded loop. In contrast to endogenous CgB, E2/3-AT-E2/3 does not undergo Ca2+/pH-dependent aggregation in the TGN. Furthermore, the disulfide-bonded loop of CgB mediates membrane binding in the TGN and does so with 5-fold higher efficiency if two loops are present on the reporter protein. The latter finding supports the concept that under physiological conditions, aggregates of CgB are the sorted units of cargo which have multiple loops on their surface leading to high membrane binding and sorting efficiency of CgB in the TGN. (+info)Identification of DNA polymorphisms associated with the V type alpha1-antitrypsin gene. (2/1525)
alpha1-Antitrypsin (alpha1-AT) is a highly polymorphic protein. The V allele of alpha1-AT has been shown to be associated with focal glomerulosclerosis (FGS) in Negroid and mixed race South African patients. To identify mutations and polymorphisms in the gene for the V allele of alpha1-AT in five South African patients with FGS nephrotic syndrome DNA sequence analysis and restriction fragment length polymorphisms of the coding exons were carried out. Four of the patients were heterozygous for the BstEII RFLP in exon III [M1(Val213)(Ala213)] and one patient was a M1(Ala213) homozygote. The mutation for the V allele was identified in exon II as Gly-148 (GGG)-->Arg (AGG) and in all patients was associated with a silent mutation at position 158 (AAC-->AAT). The patient who was homozygous for (Ala213) also had a silent mutation at position 256 in exon III (GAT-->GAC) which was not present in any of the other four patients. Although the V allele of alpha1-AT is not associated with severe plasma deficiency, it may be in linkage disequilibrium with other genes on chromosome 14 that predispose to FGS. Furthermore, the associated silent mutation at position 158 and the Ala213 polymorphism are of interest, as these could represent an evolutionary intermediate between the M1(Ala213) and M1(Val213) subtypes. (+info)The Pseudomonas aeruginosa secretory product pyocyanin inactivates alpha1 protease inhibitor: implications for the pathogenesis of cystic fibrosis lung disease. (3/1525)
Alpha1 Protease inhibitor (alpha1PI) modulates serine protease activity in the lung. Reactive oxygen species inactivate alpha1PI, and this process has been implicated in the pathogenesis of a variety of forms of lung injury. An imbalance of protease-antiprotease activity is also detected in the airways of patients with cystic fibrosis-associated lung disease who are infected with Pseudomonas aeruginosa. P. aeruginosa secretes pyocyanin, which, through its ability to redox cycle, induces cells to generate reactive oxygen species. We tested the hypothesis that redox cycling of pyocyanin could lead to inactivation of alpha1PI. When alpha1PI was exposed to NADH and pyocyanin, a combination that results in superoxide production, alpha1PI lost its ability to form an inhibitory complex with both porcine pancreatic elastase (PPE) and trypsin. Similarly, addition of pyocyanin to cultures of human airway epithelial cells to which alpha1PI was also added resulted in a loss of the ability of alpha1PI to form a complex with PPE or trypsin. Neither superoxide dismutase, catalase, nor dimethylthiourea nor depletion of the media of O2 to prevent formation of reactive oxygen species blocked pyocyanin-mediated inactivation of alpha1PI. These data raise the possibility that a direct interaction between reduced pyocyanin and alpha1PI is involved in the process. Consistent with this possibility, pretreatment of alpha1PI with the reducing agent beta-mercaptoethanol also inhibited binding of trypsin to alpha1PI. These data suggest that pyocyanin could contribute to lung injury in the P. aeruginosa-infected airway of cystic fibrosis patients by decreasing the ability of alpha1PI to control the local activity of serine proteases. (+info)Oligosaccharide modification in the early secretory pathway directs the selection of a misfolded glycoprotein for degradation by the proteasome. (4/1525)
The role of conformation-based quality control in the early secretory pathway is to eliminate misfolded polypeptides and unassembled multimeric protein complexes from the endoplasmic reticulum, ensuring the deployment of only functional molecules to distal sites. The intracellular fate of terminally misfolded human alpha1-antitrypsin was examined in hepatoma cells to identify the functional role of asparagine-linked oligosaccharide modification in the selection of glycoproteins for degradation by the cytosolic proteasome. Proteasomal degradation required physical interaction with the molecular chaperone calnexin. Altered sedimentation of intracellular complexes following treatment with the specific proteasome inhibitor lactacystin, and in combination with mannosidase inhibition, revealed that the removal of mannose from attached oligosaccharides abrogates the release of misfolded alpha1-antitrypsin from calnexin prior to proteasomal degradation. Intracellular turnover was arrested with kifunensine, implicating the participation of endoplasmic reticulum mannosidase I in the disposal process. Accelerated degradation occurred in a mannosidase-independent manner and was arrested by lactacystin, in response to the posttranslational inhibition of glucosidase II, demonstrating that the attenuated removal of glucose from attached oligosaccharides functions as the underlying rate-limiting step in the proteasome-mediated pathway. A model is proposed in which the removal of mannose from multiple attached oligosaccharides directs calnexin in the selection of misfolded alpha1-antitrypsin for degradation by the proteasome. (+info)Enhanced tumor growth and invasiveness in vivo by a carboxyl-terminal fragment of alpha1-proteinase inhibitor generated by matrix metalloproteinases: a possible modulatory role in natural killer cytotoxicity. (5/1525)
Matrix metalloproteinases (MMPs) are believed to contribute to the complex process of cancer progression. They also exhibit an alpha1-proteinase inhibitor (alphaPI)-degrading activity generating a carboxyl-terminal fragment of approximately 5 kd (alphaPI-C). This study reports that overexpression of alphaPI-C in S2-020, a cloned subline derived from the human pancreas adenocarcinoma cell line SUIT-2, potentiates the growth capability of the cells in nude mice. After stable transfection of a vector containing a chimeric cDNA encoding a signal peptide sequence of tissue inhibitor of metalloproteinase-1 followed by cDNA for alphaPI-C into S2-020 cells, three clones that stably secrete alphaPI-C were obtained. The ectopic expression of alphaPI-C did not alter in vitro cellular growth. However, subcutaneous injection of the alphaPI-C-secreting clones resulted in tumors that were 1.5 to 3-fold larger than those of control clones with an increased tendency to invasiveness and lymph node metastasis. These effects could be a result of modulation of natural killer (NK) cell-mediated control of tumor growth in nude mice, as the growth advantage of alphaPI-C-secreting clones was not observed in NK-depleted mice, and alphaPI-C-secreting clones showed decreased NK sensitivity in vitro. In addition, production of alphaPI and generation of the cleaved form of alphaPI by MMP were observed in various human tumor cell lines and in a highly metastatic subline of SUIT-2 in vitro. These results provide experimental evidence that the alphaPI-degrading activity of MMPs may play a role in tumor progression not only via the inactivation of alphaPI but also via the generation of alphaPI-C. (+info)Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis. (6/1525)
Various treatment regimens and difficulties with research design are encountered with cystic fibrosis (CF) because no standard diagnostic criteria exist for defining acute respiratory exacerbations. This study evaluated the role of serial monitoring of concentrations of selected cytokines and inflammatory mediators in serum and sputum as predictors of respiratory exacerbation, as useful outcome measures for CF, and to guide therapy. Interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), neutrophil elastase-alpha-1-protease inhibitor complex (NE complex), protein, and alpha-1-protease inhibitor (alpha-1-PI) were measured in serum and sputum collected from CF patients during respiratory exacerbations and periods of well-being. Levels of NE complex, protein, and alpha-1-PI in sputum rose during respiratory exacerbations and fell after institution of antibiotic therapy (P = 0.078, 0.001, and 0.002, respectively). Mean (+/- standard error of the mean) levels of IL-8 and TNF-alpha were extremely high in sputum (13,780 +/- 916 and 249.4 +/- 23.5 ng/liter, respectively) but did not change significantly with clinical deterioration of the patient (P > 0.23). IL-8 and TNF-alpha were generally undetectable in serum, and therefore these measures were unhelpful. Drop in forced expiratory volume in 1 s was the only clinical or laboratory parameter that was close to being a determinant of respiratory exacerbation (P = 0.055). This study provides evidence of intense immunological activity occurring continually within the lungs of adult CF patients. Measurement of cytokines and inflammatory mediators in CF sputum is not helpful for identifying acute respiratory exacerbations. (+info)Probing the unfolding pathway of alpha1-antitrypsin. (7/1525)
Protein misfolding plays a role in the pathogenesis of many diseases. alpha1-Antitrypsin misfolding leads to the accumulation of long chain polymers within the hepatocyte, reducing its plasma concentration and predisposing the patient to emphysema and liver disease. In order to understand the misfolding process, it is necessary to examine the folding of alpha1-antitrypsin through the different structures involved in this process. In this study we have used a novel technique in which unique cysteine residues were introduced at various positions into alpha1-antitrypsin and fluorescently labeled with N, N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)ethylenediamine. The fluorescence properties of each protein were studied in the native state and as a function of guanidine hydrochloride-mediated unfolding. The studies found that alpha1-antitrypsin unfolded through a series of intermediate structures. From the position of the fluorescence probes, the fluorescence quenching data, and the molecular modeling, we show that unfolding of alpha1-antitrypsin occurs via disruption of the A and C beta-sheets followed by the B beta-sheet. The implications of these data on both alpha1-antitrypsin function and polymerization are discussed. (+info)A kinetic mechanism for the polymerization of alpha1-antitrypsin. (8/1525)
The mutation in the Z deficiency variant of alpha1-antitrypsin perturbs the structure of the protein to allow a unique intermolecular linkage. These loop-sheet polymers are retained within the endoplasmic reticulum of hepatocytes to form inclusions that are associated with neonatal hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. The process of polymer formation has been investigated here by intrinsic tryptophan fluorescence, fluorescence polarization, circular dichroic spectra and extrinsic fluorescence with 8-anilino-1-naphthalenesulfonic acid and tetramethylrhodamine-5-iodoacetamide. These biophysical techniques have demonstrated that alpha1-antitrypsin polymerization is a two-stage process and have allowed the calculation of rates for both of these steps. The initial fast phase is unimolecular and likely to represent temperature-induced protein unfolding, while the slow phase is bimolecular and associated with loop-sheet interaction and polymer formation. The naturally occurring Z, S, and I variants and recombinant site-directed reactive loop and shutter domain mutants of alpha1-antitrypsin were used to demonstrate the close association between protein stability and rate of alpha1-antitrypsin polymerization. Taken together, these data allow us to propose a kinetic mechanism for alpha1-antitrypsin polymer formation that involves the generation of an unstable intermediate, which can form polymers or generate latent protein. (+info)DeficiencyAlpha1-antitrypsinAntibodySERPINA1A1ATProteaseAntibodiesAATDProteinaseProteinsEnzymeSevereHumanVariantsPhaseEmphysemaHuman Alpha-1 AntitrypsEnough alpha-1 antitrypsProtease inhibitorLevels of alpha-1 antitrypsLungsSerumProtein alpha-1 antitrypsAbnormalAugmentation TherapyLung diseaseSymptomsPhenotypesCOPDAbstractPanniculitisAssociated with Alpha-1 antitrypChronic obstrucCirrhosisMutationsA1ADPhenotypePatientsDiagnosisHepatocytesApproximately 1 in 2,500 individualsGenotypeInflammationStudied alpha-1 antitrypNewbornsAnti-trypsinHereditary disorderIntravenous infusionsSerpinProduced in the liverDisorderAlleleJaundice2018
Deficiency7
- When the blood contains inadequate amounts of A1AT or functionally defective A1AT (such as in alpha-1 antitrypsin deficiency), neutrophil elastase is excessively free to break down elastin, degrading the elasticity of the lungs, which results in respiratory complications, such as chronic obstructive pulmonary disease, in adults. (wikipedia.org)
- Disorders of this protein include alpha-1 antitrypsin deficiency, an autosomal codominant hereditary disorder in which a deficiency of alpha-1 antitrypsin leads to a chronic uninhibited tissue breakdown. (wikipedia.org)
- α(1)-Antitrypsin (α1AT) deficiency is a disease with multiple manifestations, including cirrhosis and emphysema, caused by the accumulation of stable polymers of mutant protein in the endoplasmic reticulum of hepatocytes. (rcsb.org)
- Alpha 1 anti-trypsin (AAT) deficiency is a rare genetic disorder that causes the enzyme AAT to not work well. (doctors-hospital.net)
- Alpha-1 antitrypsin (AAT) deficiency is caused by a single nucleotide substitution, which may cause chronic obstructive pulmonary disease(COPD), emphysema, liver fibrosis, or cirrhosis. (ufl.edu)
- Defects in SERPINA1 are the cause of alpha-1-antitrypsin deficiency (A1ATD). (mybiosource.com)
- The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency. (rcsi.com)
Alpha1-antitrypsin3
- The disease results from a mutation leading to the production of a misfolded protein alpha1-antitrypsin ( AAT ) in the liver, that causes a "gain-of-function toxicity" through its polymerization and retention. (rare-liver.eu)
- The gene encoding for alpha1-antitrypsin (SERPINA1) is localized on the long arm of chromosome 14. (rare-liver.eu)
- Patients with severe lung disease may require inhalative treatment, long-term oxygen therapy as well as augmentation therapy with intravenous application of purified alpha1-antitrypsin. (rare-liver.eu)
Antibody5
- Each Serpin A1/alpha 1-Antitrypsin Antibody is fully covered by our Guarantee+, to give you complete peace of mind and the support when you need it. (novusbio.com)
- Choose from our Serpin A1/alpha 1-Antitrypsin polyclonal antibodies and browse our Serpin A1/alpha 1-Antitrypsin monoclonal antibody catalog. (novusbio.com)
- Western Blot analysis of SERPINA1 expression in transfected 293T cell line ( H00005265-T01 ) by SERPINA1 MaxPab polyclonal antibody.Lane 1: SERPINA1 transfected lysate(46.70 KDa).Lane 2: Non-transfected lysate. (acris-antibodies.com)
- WB Suggested Anti-SERPINA1 Antibody Titration: 0.2-1 ug/ml. (acris-antibodies.com)
- For each experiment, 500ul of DDK tagged SERPINA1 overexpression lysates (at 1:5 dilution with HEK293T lysate), 2 ug of anti-SERPINA1 antibody and 20ul (0.1 mg) of goat anti-mouse conjugated magnetic beads were mixed and incubated overnight. (acris-antibodies.com)
SERPINA11
- Lane 1 : SERPINA1 isolated from human plasma. (acris-antibodies.com)
A1AT3
- Alpha-1-antitrypsin or α1-antitrypsin (A1AT, A1A, or AAT) is a protein belonging to the serpin superfamily. (wikipedia.org)
- Like all serine protease inhibitors, A1AT has a characteristic secondary structure of beta sheets and alpha helices. (wikipedia.org)
- Alpha-1-antitrypsin (A1AT) is a glycoprotein of MW 54 kDa with a pI of 4.8. (mybiosource.com)
Protease1
- the terms α1-antitrypsin and protease inhibitor (Pi) are often used interchangeably. (wikipedia.org)
Antibodies1
- Our Serpin A1/alpha 1-Antitrypsin Antibodies can be used in a variety of model species: Canine, Human, Mouse, Primate, Rat. (novusbio.com)
AATD1
- Also searched for Alpha 1 Proteinase Inhibitor and AATD . (clinicaltrials.gov)
Proteinase2
- Another name used is alpha-1 proteinase inhibitor (α1-PI). (wikipedia.org)
- The serine proteinase inhibitor α-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. (rcsi.com)
Proteins1
- The Company uses its proprietary platform technology and know-how for the extraction and purification of proteins from human plasma to produce Alpha-1 Antitrypsin (AAT) in a highly-purified, liquid form, as well as other plasma-derived Immune globulins. (kamada.com)
Enzyme1
- The protein was initially named "antitrypsin" because of its ability to bind and irreversibly inactivate the enzyme trypsin in vitro covalently. (wikipedia.org)
Severe1
- The prevalence of the severe forms is approximately 1 in 2500 individuals. (rare-liver.eu)
Human1
- No AM06341SU-N against human plasma (Lane 1) and NIH/3T3 cell lysate (Lane 2). (acris-antibodies.com)
Variants1
- Over 100 different variants of α1-antitrypsin have been described in various populations. (wikipedia.org)
Phase3
- A Phase 1/2 clinical trial with G1-AAT IV for the treatment of steroid refractory GvHD is currently ongoing at the Fred Hutchinson Cancer Research Center in Seattle, WA, in collaboration with Shire. (kamada.com)
- The interim data generated in the ongoing Phase 1/2 clinical trial provide us with initial evidence of the potential of Kamada's G1-AAT IV as an option to treat GvHD, if validated in the Phase 2/3 study. (kamada.com)
- The previously completed interim analysis from the Phase 1/2 clinical trial indicated that continuous administration of G1-AAT IV as a therapy for steroid-refractory gut GvHD is feasible in this subject population. (kamada.com)
Emphysema27
- α1-antitrypsin deficiency has been associated with a number of diseases: Cirrhosis COPD Pneumothorax Asthma Granulomatosis with polyangiitis Pancreatitis Gallstones Bronchiectasis Pelvic organ prolapse Primary sclerosing cholangitis Autoimmune hepatitis Emphysema, predominantly involving the lower lobes and causing bullae Secondary membranoproliferative glomerulonephritis Cancer Hepatocellular carcinoma (liver) Bladder carcinoma Gallbladder cancer Lymphoma Lung cancer Serpin peptidase inhibitor, clade A, member 1 (SERPINA1) is the gene that encodes the protein alpha-1 antitrypsin. (wikipedia.org)
- Winnie GB, Boas SR. A 1 -antitrypsin deficiency and emphysema. (ucsfhealth.org)
- Talecris Biotherapeutics announced today the publication of combined data from two studies demonstrating that augmentation therapy with Alpha(1)-Proteinase Inhibitor (Human) (A1PI) significantly reduces lung tissue loss in patients with emphysema related to Alpha(1)-antitrypsin (AAT) deficiency. (news-medical.net)
- GLASSIATM is the first available ready-to-use liquid alpha1-proteinase inhibitor (Alpha1-PI) and is indicated as a chronic augmentation and maintenance therapy in adults with emphysema due to congenital deficiency of alpha-1 antitrypsin (AAT), an under-diagnosed hereditary condition characterized by a low level of alpha-1 protein in the blood. (news-medical.net)
- Alpha-1 antitrypsin deficiency-associated lung disease is characterized by progressive degenerative and destructive changes in the lungs (emphysema, commonly of the panacinar type). (rarediseases.org)
- α(1)-Antitrypsin (α1AT) deficiency is a disease with multiple manifestations, including cirrhosis and emphysema, caused by the accumulation of stable polymers of mutant protein in the endoplasmic reticulum of hepatocytes. (rcsb.org)
- Illnesses that can accompany alpha-1 or be diagnosed instead of alpha-1 include: chronic obstructive pulmonary disease, emphysema, asthma, as well as others. (medium.com)
- Depending on the genetic variant, alpha-1 antitrypsin deficiency can lead to chronic obstructive pulmonary disease ( COPD ) or emphysema and can cause liver disease . (snpedia.com)
- OBJECTIVE: To investigate the severity of bronchiectasis and associated emphysema and the correlation with phenotype in patients with Alpha-1 antitrypsin deficiency. (biomedsearch.com)
- Fourteen patients (54%) had a degree of dilatation score of 1 or more, all had a ZZ phenotype, and 4 (15%) had no evidence of emphysema. (biomedsearch.com)
- The Role of Alpha-1 Antitrypsin in Emphysema, Emphysema Ravi Mahadeva, IntechOpen, DOI: 10.5772/31447. (intechopen.com)
- SERPINA1 encodes the alpha-1 antitrypsin (AAT) protein, and severe deficiency of AAT is a major contributor to pulmonary emphysema and liver diseases. (nih.gov)
- Adults can also be affected by Alpha-1 and may develop lung conditions such as emphysema as well as liver problems. (liverfoundation.org)
- Those with alpha 1-antitrypsin deficiency may develop emphysema. (sharecare.com)
- When alpha one antitrypsin is deficient, elastase enzymes can damage and scar lung tissue causing emphysema. (dermnetnz.org)
- Human plasma-derived α 1-antitrypsin (AAT) delivered by intravenous infusion is used as augmentation therapy in patients with emphysema who have a genetic mutation resulting in deficiency of AAT. (hindawi.com)
- Alpha-1 antitrypsin deficiency is congenital lack of a primary lung antiprotease, alpha-1 antitrypsin, which leads to increased protease-mediated tissue destruction and emphysema in adults. (merckmanuals.com)
- In the lungs, alpha-1 antitrypsin deficiency increases neutrophil elastase activity, which facilitates tissue destruction leading to emphysema (especially in smokers, because cigarette smoke also increases protease activity). (merckmanuals.com)
- The normal PI phenotype is PI*MM. More than 95% of people with severe alpha-1 antitrypsin deficiency and emphysema are homozygous for the Z allele (PI*ZZ) and have alpha-1 antitrypsin levels of about 30 to 40 mg/dL (5 to 6 micromol/L). Prevalence in the general population is 1/1500 to 1/5000. (merckmanuals.com)
- In those with Alpha-1, the inflammation and development of panniculitis has a clear similarity to the development of emphysema. (alpha1canada.ca)
- Centrilobular emphysema (most common, smoking), panlobular emphysema (predominant pattern in alpha-1-antitrypsin deficiency), paraseptal emphysema, and paracicatricial emphysema. (radiopaedia.org)
- What does the alpha-1-antitrypsin protein do and how is its absence responsible for emphysema? (radiopaedia.org)
- Severe mid and lower zone emphysema (panlobular) in a patient with alpha-1-antitrypsin deficiency. (radiopaedia.org)
- Cigarette smoking may cause emphysema by inactivating alpha 1-antitrypsin through oxidation. (sciencemag.org)
- Alpha-1-antitrypsin (A1AT) deficiency is a hereditary metabolic disorder and is the most common genetic cause of emphysema and metabolic liver disease in children. (radiopaedia.org)
- Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment. (radiopaedia.org)
- Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS. (umassmed.edu)
Human Alpha-1 Antitryps6
- Human alpha 1-antitrypsin (AAT), a serum glycoprotein, is one of the best-known models of serine protease inhibitors (serpins) superfamily [1, (thefreedictionary.com)
- Human alpha 1-antitrypsin (AAT) cDNA was obtained from HepG2 cell lines. (thefreedictionary.com)
- 7 June 2011 - US biopharmaceutical company Halozyme Therapeutics Inc (NASDAQ: HALO) and US-based synthetic biology company Intrexon Corp signed yesterday a worldwide exclusive licensing agreement for the use of rHuPH20 (recombinant human hyaluronidase) in the development of a subcutaneous injectable formulation of Intrexon's recombinant human alpha 1-antitrypsin (rHuA1AT). (thefreedictionary.com)
- Product is the lyophilized powder of horseradish peroxidase (HRP)-conjugated goat IgG fraction to human alpha-1-antitrypsin and buffer salts. (mpbio.com)
- Fu D.A., Campbell-Thompson M. (2017) Immunohistochemistry Staining for Human Alpha-1 Antitrypsin. (springer.com)
- Human alpha-1 antitrypsin protects the lungs from the harmful effects of human neutrophil elastase. (leebio.com)
Enough alpha-1 antitryps4
- Individuals with an MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs. (medlineplus.gov)
- It occurs when the liver doesn't release enough alpha-1 antitrypsin protein, which helps the lungs function properly. (medium.com)
- People who have two damaged copies of the gene are not able to produce enough alpha- 1 antitrypsin, which leads them to have more severe symptoms. (genome.gov)
- When the lungs do not have enough alpha-1 antitrypsin, neutrophil elastase is free to destroy tissue. (chp.edu)
Protease inhibitor5
- the terms α1-antitrypsin and protease inhibitor (Pi) are often used interchangeably. (wikipedia.org)
- Alpha-1-antitrypsin (AAt) is a serine protease inhibitor produced primarily in the liver. (mayoclinic.org)
- Please refer to the alpha 1-antitrypsin for the various protease inhibitor (Pi) genotypes and phenotypes. (doctorslounge.com)
- Alpha 1 antitrypsin is a type of plasma protein inside our body, it is called protease inhibitor. (mynewsdesk.com)
- Alpha-1-antitrypsin (AAT) is the chief protease inhibitor (PI) in human serum. (arupconsult.com)
Levels of alpha-1 antitryps9
- The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of alpha-1 antitrypsin. (medlineplus.gov)
- Other versions of the SERPINA1 gene lead to reduced levels of alpha-1 antitrypsin. (medlineplus.gov)
- Normal blood levels of alpha-1 antitrypsin may vary with analytical method but are typically around 1.0-2.7 g/l. (wikipedia.org)
- The randomized, double-blind, placebo-controlled Phase 2 study of approximately 50 patients was designed to evaluate the safety and PK of VX-814, and the ability of VX-814 to increase functional levels of alpha-1 antitrypsin over 28 days of dosing. (nasdaq.com)
- Normal blood levels of alpha-1 antitrypsin are 1.5-3.5 gm/l. (bionity.com)
- Alpha 1-antitrypsin deficiency (A1AD) is a genetic disorder caused by reduced levels of alpha 1-antitrypsin in blood. (doctorslounge.com)
- The diagnosis of Alpha-1 is made by blood tests showing the low levels of alpha-1 antitrypsin and abnormal liver tests. (liverfoundation.org)
- Alpha-1 antitrypsin deficiency is a common hereditary disorder characterized by reduced levels of alpha-1 antitrypsin. (chp.edu)
- Panniculitis in Alpha-1 is found in different phenotypes, some with severe deficiency of serum levels of Alpha-1 Antitrypsin (typically PI*ZZ) and others with only mild deficiency (typically PI*MZ). (alpha1canada.ca)
Lungs15
- Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (especially the lungs) if not tightly controlled by alpha-1 antitrypsin. (medlineplus.gov)
- If Jackson has alpha-1 antitrypsin deficiency, it means he cannot protect his lungs from his body's own defenses against bacteria. (scientificamerican.com)
- This is a multi-center, randomized, placebo-controlled, double blind clinical study to assess the efficacy and safety of two separate dose regimens of Alpha-1 MP versus placebo for 156 weeks (i.e., 3 years) using computed tomography (CT) of the lungs as the main measure of efficacy. (centerwatch.com)
- Patients with alpha-1 antitrypsin deficiency cannot produce a protective form of the protein alpha-1 antitrypsin, which is normally produced in the liver and protects the lungs from inflammation. (news-medical.net)
- Deficiency of alpha-1 antitrypsin results in unbalanced (i.e., relatively unopposed) rapid breakdown of proteins (protease activity), especially in the supporting elastic structures of the lungs. (rarediseases.org)
- Alpha-1 antitrypsin (AAT) is a protein normally found in the lungs and the bloodstream. (northshore.org)
- 1 When AAT is functioning abnormally it cannot be released from the liver to reach the lungs, which creates a buildup. (businesswire.com)
- Treatment for alpha-1 antitrypsin deficiency involves avoiding substances-especially cigarette smoke-that could harm your lungs. (lmh.org)
- Alpha-1 antitrypsin (AAT) deficiency is a condition in which the body does not make enough of AAT, a protein that protects the lungs and liver from damage. (mountsinai.org)
- In normal lungs, alpha-1 antitrypsin protects lung tissue by trapping and destroying neutrophil elastase before it has a chance to outlive its usefulness and cause damage. (chp.edu)
- Alpha-1 antitrypsin deficiency (AADT) is an inherited disease of the liver and lungs. (chp.edu)
- Alpha-1 antitrypsin is a neutrophil elastase inhibitor (an antiprotease), the major function of which is to protect the lungs from protease-mediated tissue destruction. (merckmanuals.com)
- In its absence (such as in alpha 1-anti-trypsin deficiency), neutrophil elastase is free to break down elastin, which contributes to the elasticity of the lungs. (medindia.net)
- In both the skin and the lungs of Alphas, there is a lack of Alpha-1 Antitrypsin, which normally balances the action of proteases - enzymes that break down proteins as part of normal body functioning. (alpha1canada.ca)
- We reviewed the benefits and harms of treating patients who have the form of the disease that affects the lungs with alpha-1 antitrypsin extracted from blood donations. (cochrane.org)
Serum10
- Alpha 1 -antitrypsin - serum. (ucsfhealth.org)
- The laboratory evaluation includes serum alpha-1-antitrypsin level measurement (normal 100 to 190 mg/dL). (mayoclinic.org)
- Alpha-1-antitrypsin phenotypes of umbilical cord serum from 741 Polish newborns were studied by isoelectric focusing. (biomedsearch.com)
- This project is designed to examine the interaction between the microflora in the lower airway and the concentration of a serum protein called alpha-1 antitrypsin. (clinicaltrials.gov)
- Alpha-1 antitrypsin (AAT) is the most abundant serum and lung antiprotease and has a variety of biologic activities that influence lung homeostasis. (clinicaltrials.gov)
- The electrophoretic alpha-1-globin pattern of serum alpha-1-antitrypsin deficiency. (thefreedictionary.com)
- The cartridges use affinity-purified polyclonal antibodies to remove more than 98 percent of the six most abundant proteins (albumin, immunoglobulin G, immunoglobulin A, alpha-1-antitrypsin , transferrin and haptoglobin) in human serum and the three most abundant proteins (albumin, immunoglobulin G and transferrin) in mouse serum, with minimal non-specific removal of other proteins. (thefreedictionary.com)
- Serum alpha 1-antitrypsin deficiency associated with the common S-type (glu264--val) mutation results from intracellular degradation of alpha 1-antitrypsin prior to secretion. (thefreedictionary.com)
- The α-1AT, 52KD glycoprotein, is the most abundant inhibitory human serum proteases [ 1 ] has significant anti-inflammatory properties (blocked cytotoxicity conducted by neutrophils and stimulating síntetis IL-8, IL-6, IL1β, TNF α- and other cytokines), increasing their activity in inflammatory, tumoral or infectious processes [ 2 ]. (omicsonline.org)
- Samples of human serum obtained immediately after smoking also show decreased elastase inhibitory capacity per milligram of alpha 1-antitrypsin. (sciencemag.org)
Protein alpha-1 antitryps1
- Prolastin C replaces the naturally-occurring protein alpha 1-antitrypsin with alpha 1-proteinase inhibitor to treat alpha 1-antitrypsin deficiency. (sharecare.com)
Abnormal9
- Abnormal alpha-1 antitrypsin can also accumulate in the liver and damage this organ. (medlineplus.gov)
- Alpha-1 may also appear in late childhood or adulthood and be detected because of fatigue, poor appetite, swelling of the abdomen and legs or abnormal liver tests. (liverfoundation.org)
- If your AAT level is lower than normal, the blood sample can be tested to look for abnormal types of alpha-1 antitrypsin. (lmh.org)
- In addition, the abnormal alpha-1 is often defective, so that the small amount released cannot effectively "trap" the neutrophil elastase in time. (chp.edu)
- Hepatic accumulation of abnormal alpha-1 antitrypsin can cause liver disease in both children and adults. (merckmanuals.com)
- When the Alpha-1 protein is missing or abnormal and not functioning, this balance breaks down. (alpha1canada.ca)
- Most Alpha-1 liver research suggests that the abnormal Alpha-1 Antitrypsin protein cannot move from the liver cells (where it is made) out into the bloodstream because the protein does not fold normally. (alpha1canada.ca)
- The buildup of abnormal Alpha-1 protein inside the liver cells can cause stress and irritation in the liver, which may eventually lead to scarring (or fibrosis) in the liver. (alpha1canada.ca)
- When a liver biopsy from an individual with Alpha-1 is examined under a microscope the liver cells appear filled with granules, which are actually abnormal Alpha-1 Antitrypsin protein that can't be cleared from the liver. (alpha1canada.ca)
Augmentation Therapy6
- A stage 1, prospective, randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of Alpha 1-proteinase Inhibitor (A1P1) augmentation therapy in subjects with A1P1 Deficiency and chronic obstructive pulmonary disease (COPD). (centerwatch.com)
- 2012). Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: A Canadian Thoracic Society clinical practice guideline. (alberta.ca)
- Various therapies have been tried for panniculitis, including panniculitis due to Alpha-1, among them corticosteroids, antibiotics (including doxycycline and dapsone), the complete exchange of the body's blood plasma, and augmentation therapy - intravenous infusions of donated Alpha-1 protein. (alpha1canada.ca)
- In panniculitis due to Alpha-1, augmentation therapy has been the most dramatically successful of these therapies. (alpha1canada.ca)
- Therefore, it is our opinion that augmentation therapy with alpha-1 antitrypsin cannot be recommended. (cochrane.org)
- We included randomised trials of augmentation therapy with alpha-1 antitrypsin compared with placebo or no treatment. (cochrane.org)
Lung disease12
- Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. (medlineplus.gov)
- People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. (medlineplus.gov)
- Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys alveoli and causes lung disease. (medlineplus.gov)
- The gastrointestinal bleeding may be unrelated to alpha-1 antitrypsin deficiency, but to the extent that the deficiency is associated with liver and lung disease, one could develop stomach bleeding. (scientificamerican.com)
- Alpha-1 Antitrypsin Deficiency is a genetic (inherited) condition that may result in serious lung disease in adults and/or liver disease at any age. (centerwatch.com)
- The Alpha-1 Foundation announced today that it has awarded two research grants to investigators whose research will contribute to our understanding of the causes and mechanisms that give rise to lung disease. (news-medical.net)
- Those lacking alpha-1 antitrypsin are vulnerable to infections or irritants in the air, such as cigarette smoke, and often develop life-threatening lung disease. (news-medical.net)
- EXPERT ANALYSIS FROM THE INTERNATIONAL CONFERENCE OF THE AMERICAN THORACIC SOCIETY DENVER - Screening for alpha-1 antitrypsin deficiency has benefits in appropriately selected patients with lung disease and their family members, according to Dr. (acronymfinder.com)
- The pathophysiology (functional changes associated with or resulting from disease or injury) of liver disease in alpha-1 antitrypsin deficiency is less understood than that of the associated lung disease. (chp.edu)
- Lung disease is much more severe in smokers than in non-smokers with alpha-1 antitrypsin deficiency. (dermnetnz.org)
- Brebner JA, Stockley RA (2013) Recent advances in α-1-antitrypsin deficiency-related lung disease. (springer.com)
- The causes of liver disease in Alpha-1 are less understood than the causes of lung disease in this condition. (alpha1canada.ca)
Symptoms9
- Play media Symptoms of alpha-1 antitrypsin deficiency include shortness of breath, wheezing, rhonchi, and rales. (wikipedia.org)
- Currently, the only limitedly effective treatment for patients with serious breathing symptoms involves weekly intravenous injections of alpha-1 protein derived from human plasma. (news-medical.net)
- Symptoms that can be present with alpha-1 antitrypsin include shortness of breath, chronic respiratory infections with or without mucous, low oxygen saturation levels, a large decrease in lung function in a small amount of time, as well as others. (medium.com)
- Alpha-1 affects approximately 1 in 2,000 to 1 in 5,000 individuals but it is often misdiagnosed or underdiagnosed because the initial symptoms may mimic other conditions, such as asthma or chronic obstructive pulmonary disease (COPD). (businesswire.com)
- What are the symptoms of Alpha-1 Antitrypsin Deficiency? (liverfoundation.org)
- In newborns, the typical symptoms of Alpha-1 are jaundice, swelling of the abdomen, and poor feeding. (liverfoundation.org)
- For many people with rare illnesses such as lysosomal storage disease, hemophilia, Guillain-Barre syndrome, and Alpha-1-antitrypsin deficiency disease, specialty pharmaceuticals represent their standard of care, keeping symptoms stable and helping to reclaim quality of life. (thefreedictionary.com)
- Providing a value-added level of insight from the analysis team at Black Swan, several of the main symptoms and co-morbidities of Alpha-1 Anti-Trypsin have been quantified and presented alongside the overall prevalence figures. (medindia.net)
- Respiratory symptoms and lung function in 30-year-old individuals with alpha-1-antitrypsin deficiency. (lu.se)
Phenotypes3
- Please see alpha 1-antitrypsin for a discussion of the various genotypes and phenotypes associated with A1AD. (bionity.com)
- After getting each patient Alpha 1 Antitrypsin phenotype by means of Isoelectrofocusing with polyacrylamyde plates (pH 4-5), it was verified that the group without Atopic Dermatitis had more MS phenotypes in statistically significant quantities (p less than 0.005) and those with Atopic Dermatitis showed more variety of MZ phenotypes (p less than 0,025). (eurekamag.com)
- Fev\(_1\) percent of predicted and Fev\(_1\)/FVC ratio were analyzed as quantitative phenotypes. (harvard.edu)
COPD9
- Many individuals with alpha-1 antitrypsin deficiency are likely undiagnosed, particularly people with a lung condition called chronic obstructive pulmonary disease (COPD). (medlineplus.gov)
- If you have Chronic Obstructive Pulmonary Disease (COPD), you need to know about Alpha-1 Antitrypsin Deficiency. (centerwatch.com)
- In this episode of Big Ideas Theater, Robert Sandhaus, PhD, MD, FCCP, discusses Alpha-1 Antitrypsin Deficiency and the importance of testing it as a cause for COPD. (aarc.org)
- Some 5,000 COPD patients will be tested to determine the prevalence of Alpha-1 Antitrypsin Deficiency (Alpha-1) in a study marking a major cooperative effort between the Alpha-1 Foundation and the American Association for Respiratory Care (AARC). (acronymfinder.com)
- This study investigated the role of alpha 1 -antitrypsin deficiency (α 1 ATD), chronic obstructive pulmonary disease (COPD) and tobacco smoke exposure in lung cancer development in 1856 patients with lung cancer. (bmj.com)
- The findings suggest that α 1 ATD carriers are at a 70-100% increased risk of lung cancer, particularly adenocarcinoma and squamous cell subtypes (adjusted for the effects of tobacco smoke exposure and COPD). (bmj.com)
- Alpha-1 Antitrypsin Deficiency - A Genetic Risk Factor for COPD, Chronic Obstructive Pulmonary Disease Kian-Chung Ong, IntechOpen, DOI: 10.5772/28286. (intechopen.com)
- Alpha-1 antitrypsin deficiency accounts for 1 to 2% of all cases of chronic obstructive pulmonary disease (COPD). (merckmanuals.com)
- Background: The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. (harvard.edu)
Abstract1
- phdthesis{a13a8c55-510f-4fb9-a532-a58534436a33, abstract = {Alpha-1-antitrypsin (AAT) is a glycoprotein synthesised in the liver. (lu.se)
Panniculitis8
- In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. (medlineplus.gov)
- Panniculitis due to alpha-1 antitrypsin deficiency is rare. (dermnetnz.org)
- Males and females of any age are equally affected by the panniculitis associated with alpha-1 antitrypsin deficiency, and it can rarely arise in children. (dermnetnz.org)
- As alpha-1-antitrypsin deficiency is under-diagnosed, the true prevalence of panniculitis due to alpha-1-antitrypsin deficiency is difficult to ascertain. (dermnetnz.org)
- One study reported panniculitis affected 0.9% of ZZ homozygotes for alpha-1-antitrypsin deficiency. (dermnetnz.org)
- Physicians in France first described Panniculitis due to Alpha-1 in 1972. (alpha1canada.ca)
- Since that original report, fewer than 100 cases of panniculitis in those with Alpha-1 have been reported in the medical literature. (alpha1canada.ca)
- Undoubtedly, treatment choices for panniculitis will grow as research continues on new therapies for Alpha-1. (alpha1canada.ca)
Associated with Alpha-1 antitryp1
- It is generally thought that the liver disease associated with alpha-1 antitrypsin deficiency is not caused by the alpha-1 deficiency in the bloodstream, but by excessive amounts of alpha-1 stuck in the liver cells. (chp.edu)
Chronic obstruc1
- Inherited chronic obstructive pulmonary disease: new selective-sequencing workup for alpha-1 antitrypsin deficiency identifies 2 previously unidentified null alleles. (acronymfinder.com)
Cirrhosis1
- Some alpha-1 antitrypsin deficiency patients have cirrhosis of the liver. (chp.edu)
Mutations5
- Previous studies on stabilizing mutations of alpha(1)-antitrypsin, a prototype of serpins, indicated that cavities provide a structural basis for the native strain of the molecule. (nih.gov)
- We have systematically mapped the cavities of alpha(1)-antitrypsin that play such structural and functional roles by designing cavity-filling mutations at residues that line the walls of the cavities. (nih.gov)
- Results show that energetically unfavorable cavities are distributed throughout the alpha(1)-antitrypsin molecule, and the cavity-filling mutations stabilized the native conformation at 8 out of 10 target sites. (nih.gov)
- The stabilization effect of the individual cavity-filling mutations of alpha(1)-antitrypsin varied (0.2-1.9 kcal/mol for each additional methylene group) and appeared to depend largely on the structural flexibility of the cavity environment. (nih.gov)
- Cavity-filling mutations that decreased inhibitory activity of alpha(1)-antitrypsin were localized in the loop regions that interact with beta-sheet A distal from the reactive center loop. (nih.gov)
A1AD3
- In the United States, Canada, and several European countries, lung-affected A1AD patients may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. (bionity.com)
- Northwest Europeans are at the highest risk for A1AD, with 4% carrying the PiZ allele and - therefore - a risk of homozygosity in about 1:625 to 1:2000. (doctorslounge.com)
- Alpha-1 antitrypsin deficiency is abbreviated as A1AD. (dermnetnz.org)
Phenotype1
- Alpha-1 antitrypsin PI type of phenotype test, which determines the type of AAT protein that a person has. (genome.gov)
Patients18
- The trial established the safety of the adeno-associated virus used to 'infect' patients' cells with replacement genes, which then do the vital work of producing the alpha-1 protein. (news-medical.net)
- Data from patients with alpha 1 antitrypsin deficiency, who reported starting treatments within the last 5 years. (patientslikeme.com)
- ORLANDO, Fla.--( BUSINESS WIRE )--Today, The Assistance Fund, an independent charitable patient assistance foundation that helps patients and families facing high medical out-of-pocket costs, announced the launch of a new program for individuals with Alpha-1 Antitrypsin Deficiency (Alpha-1). (businesswire.com)
- The launch of the Alpha-1 Antitrypsin Deficiency Financial Assistance Program is an important milestone for patients living with this condition," said Mark P. McGreevy, President and CEO, The Assistance Fund. (businesswire.com)
- 1 There is no cure for Alpha-1, but once officially diagnosed by a blood test, there are a number of treatment courses patients can take. (businesswire.com)
- We look forward to the impact TAF's programs will have in reducing that burden for Alpha-1 patients and their families. (businesswire.com)
- The α 1 AT alleles were tested in 1443 patients, 797 unrelated controls and 902 full siblings. (bmj.com)
- This would expedite the process for Alpha-1 Patients that are applying for Social Security Disability Benefits. (change.org)
- 15 Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency (REDAAT), Spanish Society of Pneumology (SEPAR), Fundación Española de Pulmón (RESPIRA), Barcelona, Spain. (nih.gov)
- This affects very young alpha-1 antitrypsin deficiency children, as well as 12 - 15 percent of adult alpha-1 antitrypsin deficiency patients. (chp.edu)
- Patients with two 'ZZ' genes (homozygotes) are 85% deficient in alpha-1-antitrypsin. (dermnetnz.org)
- Effect of liver transplant on pulmonary functions in adult patients with alpha 1 antitrypsin deficiency: 7 cases. (nih.gov)
- Some patients with bronchiectasis have alpha-1 antitrypsin deficiency. (merckmanuals.com)
- Gain an understanding of the specific markets that have the largest number of Alpha-1 Anti-Trypsin patients. (medindia.net)
- The randomized control SEQUOIA study will comprise 120 patients who will receive ARO-AAT on day 1, day 29, and approximately every 12 weeks thereafter to determine safety, pharmacodynamic dose response, and efficacy during the full two-part study. (healio.com)
- Alpha-1 Canada's mission is to advocate for Canadians affected by Alpha-1 Antitrypsin Deficiency and to provide education to patients and the healthcare community to increase awareness and testing for this genetic disease. (alpha1canada.ca)
- La mission d'Alpha-1 Canada est de militer pour les canadiens qui souffrent d'un déficit en alpha 1-antitrypsine et d'offrir de la formation aux patients et à la communauté médicale afin d'augmenter la sensibilisation à cette maladie génétique et aux examens possibles. (alpha1canada.ca)
- Likewise, we identified possible biomarkers to screening of PTB patients eligible to adjuvants therapies, as anti-inflammatories and alpha-1-antitrypsin. (frontiersin.org)
Diagnosis4
- American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1-antitrypsin deficiency. (thefreedictionary.com)
- The diagnosis of alpha-1 antitrypsin deficiency liver disease can be established with the results of a simple blood test . (chp.edu)
- According to the report, one driver influencing this market is the improving diagnosis of alpha-1 antitrypsin deficiency. (benzinga.com)
- Specific medical advice will not be provided and Alpha-1 Canada urges you to consult with a qualified physician for diagnosis and for answers to your personal questions. (alpha1canada.ca)
Hepatocytes6
- As published in the March issue of Cell Transplantation, Geron scientists describe protocols that differentiate hESCs into human hepatocytes that express albumin, alpha-1-antitrypsin , glycogen and toxicity studies to be performed earlier in the drug discovery process, enabling the elimination of toxic compounds before undertaking costly human trials. (thefreedictionary.com)
- Human α 1-antitrypsin (AAT) is a serine proteinase inhibitor produced primarily by hepatocytes, macrophages, and bronchial epithelial cells [ 1 ]. (hindawi.com)
- Inheritance of some variant alleles causes a change in conformation of the alpha-1 antitrypsin molecule, leading to polymerization and retention within hepatocytes. (merckmanuals.com)
- Accumulation of altered alpha-1-antitrypsin in hepatocytes incites an inflammatory response and chronic liver disease. (radiopaedia.org)
- Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice. (jimmunol.org)
- We found that both bovine alpha 1-AGP and human alpha 1-AT also inhibited specifically the induction of apoptosis of hepatocytes by TNF/ galactosamine in vivo. (jimmunol.org)
Approximately 1 in 2,500 individuals1
- Worldwide, approximately 1 in 2,500 individuals has Alpha-1 Antitrypsin Deficiency. (liverfoundation.org)
Genotype2
- Alpha-1 genotyping, which examines a person's genes and determines their genotype. (genome.gov)
- The normal genotype is 'MM' has a normal level of alpha-1-antitrypsin. (dermnetnz.org)
Inflammation3
- Alpha-1 antitrypsin is ordinarily released by specialized, granules within a type of white blood cells (called neutrophils or polymorphonuclear leukocytes) in response to infection or inflammation. (rarediseases.org)
- As α 1 -antitrypsin is an acute phase reactant, its transcription is markedly increased during inflammation elsewhere in response to increased interleukin-1 and 6 and TNFα production. (bionity.com)
- Deficiency of alpha one antitrypsin leads to inflammation and necrosis in various organs. (dermnetnz.org)
Studied alpha-1 antitryp1
- To find out more about the condition, we spoke with James Stoller , a pulmonary critical care doctor at the Cleveland Clinic who has studied alpha-1 antitrypsin deficiency for more than 20 years. (scientificamerican.com)
Newborns2
- In newborns, alpha-1 antitrypsin deficiency has indicators that include early onset jaundice followed by prolonged jaundice. (wikipedia.org)
- Alpha-1-antitrypsin subtypes in Polish newborns. (biomedsearch.com)
Anti-trypsin7
- Alpha 1 anti-trypsin (AAT) deficiency is a rare genetic problem. (epnet.com)
- This report provides the current prevalent population for Alpha-1 Anti-Trypsin across 9 Major Markets ( USA , France , Germany , Italy , Spain , UK, Brazil , Japan and India ) split by gender and 5-year age cohort. (medindia.net)
- Reason to buy - Able to quantify patient populations in the global Alpha-1 Anti-Trypsin market to target the development of future products, pricing strategies and launch plans. (medindia.net)
- Gain further insight into the prevalence of the subdivided types of Alpha-1 Anti-Trypsin and identify patient segments with high potential. (medindia.net)
- Provide a level of understanding on the impact from specific co-morbid conditions on the Alpha-1 Anti-Trypsin prevalent population. (medindia.net)
- Identify sub-populations within Alpha-1 Anti-Trypsin which require treatment. (medindia.net)
- You have the appropriate genetic pattern of alpha 1 anti-trypsin deficiency obtained from a blood test. (alberta.ca)
Hereditary disorder1
- Disorders of this protein include alpha-1 antitrypsin deficiency, an autosomal codominant hereditary disorder in which a deficiency of alpha-1 antitrypsin leads to a chronic uninhibited tissue breakdown. (wikipedia.org)
Intravenous infusions1
- Alpha-1-antitrypsin replacement therapy, most often by weekly intravenous infusions of alpha-1-antitrypsin purified from human plasma, has been used in some situations to partially correct the biochemical defect 14,15 . (radiopaedia.org)
Serpin3
- Alpha-1-antitrypsin is a member of the Serpin family. (biocompare.com)
- Fusion protein corresponding to a region derived from 25-307 amino acids of human serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1. (acris-antibodies.com)
- A total of 245 serpin Peptidase Inhibitor, Clade A (Alpha-1 Antiproteinase, Antitrypsin), Member 7 products are currently listed. (antibodies-online.com)
Produced in the liver2
- Normally, alpha 1-antitrypsin is produced in the liver and exists in levels of 1.5-3.5 gram/litre. (doctorslounge.com)
- Alpha-1-antitrypsin is mostly produced in the liver and regulates several proteolytic enzymes including trypsin, elastase, chymotrypsin, factor VIII, collagenase and kallikrein. (dermnetnz.org)
Disorder9
- This disorder affects about 1 in 1,500 to 3,500 individuals with European ancestry. (medlineplus.gov)
- What Is Alpha-1 Antitrypsin Deficiency Disorder? (scientificamerican.com)
- According to Ian Halperin, an investigative journalist who is writing an unauthorized biography of the singer, Jackson, 50, has been fighting the genetically inherited disorder alpha-1 antitrypsin deficiency for several years. (scientificamerican.com)
- It helps find out if you have a genetic disorder called alpha-1 antitrypsin deficiency. (ahealthyme.com)
- This disorder is linked to abnormally low levels or a lack of alpha-1 antitrypsin (AAT) protein in the blood. (ahealthyme.com)
- Alpha-1 antitrypsin deficiency (Alpha-1) is a hereditary genetic disorder which may lead to the development of lung and/or liver disease. (liverfoundation.org)
- Individuals with Alpha-1 have a genetic disorder that prevents their body from creating enough of this protein. (liverfoundation.org)
- Alpha-1 antitrypsin deficiency disease is an inherited metabolic disorder in which this protein is absent or defective. (dermnetnz.org)
- It is not the intention of this website to provide specific medical advice but rather to provide the Canadian Alpha-1 Community with information to better understand their health and their diagnosed disorder. (alpha1canada.ca)
Allele2
- For example, the S allele produces moderately low levels of this protein, and the Z allele produces very little alpha-1 antitrypsin. (medlineplus.gov)
- Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency. (medlineplus.gov)
Jaundice1
- About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). (medlineplus.gov)
20183
- 2018. Retrieved from https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency . (businesswire.com)
- The Global Alpha-1 Antitrypsin Drugs Market to grow at a CAGR of 10.64% during the period 2018-2022. (benzinga.com)
- The report, Alpha-1 Antitrypsin Drugs Market 2018-2022 has been prepared based on an in-depth market analysis with inputs from industry experts. (benzinga.com)