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)

*Alpha-1 antitrypsin

DeMeo DL, Silverman EK (March 2004). "Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: ... Recombinant alpha-1 antitrypsin is not yet available for use as a drug but is under investigation as a therapy for alpha-1 ... Alpha-1-antitrypsin or α1-antitrypsin (A1AT, A1A, or AAT) is a protein belonging to the serpin superfamily. It is encoded in ... The alpha region can be further divided into two sub-regions, termed "1" and "2". Alpha-1 antitrypsin is the main protein of ...

*Pancreatic elastase

Alpha 1-antitrypsin and alpha-2-macroglobulin are human serum protease inhibitors that completely inhibit the general ... Pancreatic elastase 1 is a serine endopeptidase, a specific type of protease that has the amino acid serine at its active site ... Elastase 1 is slightly inhibited above 150 mM NaCl Mutations of the CELA1 gene were suspected to be associated with diffuse ... 12 (1): 170-6. doi:10.1111/j.1432-1033.1970.tb00835.x. PMID 5461547. "CELA1 Gene". GeneCards. Davies RL, Yoon SJ, Weissenbach J ...

*Alpha 1-antitrypsin deficiency

Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease. Onset of ... Alpha 1-antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted ... Alpha-1 antitrypsin deficiency was first described in the 1960s. Play media Symptoms of alpha-1 antitrypsin deficiency include ... A1AD is due to a mutation in the SERPINA1 gene that results in not enough alpha-1 antitrypsin (A1AT). Risk factors for lung ...

*DMOZ - Health: Conditions and Diseases: Nutritional and Metabolic Disorders: Inherited: Alpha-1 Antitrypsin Deficiency

A deficiency of the enzyme alpha 1-antitrypsin results in low levels or a lack of an essential blood protein that protects ... "Health ... Alpha-1 Antitrypsin Deficiency" search on: AOL - Ask - Bing - DuckDuckGo - Gigablast - Google - ixquick - Yahoo - ... Understanding Alpha-1 Antitrypsin Deficiency Information on signs and symptoms of this disorder, as well as risk factors and ... Canadian Liver Foundation: Alpha-1 Antitrypsin Deficiency Reviews the cause, symptoms, risk of lung and liver disease, and ...

*Cirrhosis

Alpha 1-antitrypsin deficiency (A1AD). Autosomal recessive disorder of decreased levels of the enzyme alpha 1-antitrypsin. ... but may help in distinguishing various causes Cholesterol and glucose Alpha 1-antitrypsin Ultrasound is routinely used in the ... 35 (1): 201-19. doi:10.1016/j.gtc.2005.12.007. PMID 16530121. Poonja, Z; Brisebois, A; van Zanten, SV; Tandon, P; Meeberg, G; ... 5 (1): 35-45. doi:10.1055/s-2008-1041756. PMID 3983651. van Thiel, DH; Gavaler, JS; Spero, JA; Egler, KM; Wright, C; Sanghvi, ...

*Lung transplantation

... alpha 1-antitrypsin deficiency; 2% replacing previously transplanted lungs that have since failed; 24% other causes, including ... 109 (1): 49-59. doi:10.1016/S0022-5223(95)70419-1. Merck Manual 18th ed. p. 1377 "2008 OPTN/SRTR Annual Report". US Scientific ... 1 May 2008. Archived from the original on 5 June 2010. Retrieved 28 July 2010. Arcasoy, Selim M.; Kotloff, Robert M. (1999). " ...

*Liver disease

"Alpha-1 Antitrypsin Deficiency: MedlinePlus". www.nlm.nih.gov. Retrieved 2015-06-20. Leslie, Nancy; Tinkle, Brad T. (1993). ... Liver damage is also a clinical feature of alpha 1-antitrypsin deficiency and glycogen storage disease type II. In ... 327 (1-2): 26-47. doi:10.1016/j.canlet.2012.01.016. PMID 22293091. Nishida N, Kudo M (2013). "Oxidative stress and epigenetic ... 25 (1): 142-163. doi:10.1128/CMR.00018-11. PMC 3255968 . PMID 22232374. Suk KT, Kim MY, Baik SK (September 2014). "Alcoholic ...

*Bronchiectasis

People with alpha 1-antitrypsin deficiency have been found to be particularly susceptible to bronchiectasis, due to the loss of ... Shin MS, Ho KJ (1993). "Bronchiectasis in patients with alpha 1-antitrypsin deficiency. A rare occurrence?". Chest. 104 (5): ... The disease affects between 1 per 1000 and 1 per 250,000 adults. The disease is more common in women and increases as people ... The disease affects between 1 per 1000 and 1 per 250,000 adults. The disease is more common in women and increases as people ...

*Hepcidin

Pandur E, Nagy J, Poór VS, Sarnyai A, Huszár A, Miseta A, Sipos K (April 2009). "Alpha-1 antitrypsin binds preprohepcidin ... This conversion may be regulated by alpha-1 antitrypsin. Hepcidin is a tightly folded polypeptide with 32% beta sheet character ... 93 (1): 90-7. doi:10.3324/haematol.11705. PMID 18166790. Bregman DB, Morris D, Koch TA, He A, Goodnough LT (February 2013). " ... Krause A, Neitz S, Mägert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K (September 2000). "LEAP-1, a novel highly ...

*Panniculitis

Alpha 1-antitrypsin deficiency, also, is a major cause of Panniculitis. Lipoatrophy or lipodystrophy (the loss of subcutaneous ... Alpha-1 antitrypsin deficiency panniculitis is a panniculitis associated with a deficiency of the α1-antitrypsin enzyme. ... ISBN 1-4160-2999-0. Epstein, Ervin and Oren, Mark, "Popsicle Panniculitis" "The New England Journal of Medicine", 282 (17) : ... ISBN 1-4160-2999-0. Gilchrist, H; Patterson, JW (Jul-Aug 2010). "Erythema nodosum and erythema induratum (nodular vasculitis): ...

*Chronic obstructive pulmonary disease

The effectiveness of alpha-1 antitrypsin augmentation treatment for people who have alpha-1 antitrypsin deficiency is unclear. ... In areas of the world where alpha-1 antitrypsin deficiency is common, people with COPD (particularly those below the age of 45 ... Currently, the only clearly inherited risk factor is alpha 1-antitrypsin deficiency (AAT). This risk is particularly high if ... Brode SK, Ling SC, Chapman KR (September 2012). "Alpha-1 antitrypsin deficiency: a commonly overlooked cause of lung disease". ...

*Weber-Christian disease

Alpha-1 antitrypsin deficiency panniculitis List of cutaneous conditions Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph ... ISBN 1-4160-2999-0. "Weber-Christian disease" at Dorland's Medical Dictionary Weber-Christian disease at Who Named It? Weber, F ... doi:10.1111/j.1365-2133.1925.tb10003.x. Christian, Henry Asbury (1 September 1928). "Relapsing febrile nodular nonsuppurative ...

*Health of Frédéric Chopin

A hypothesis of alpha 1-antitrypsin deficiency was proposed by Kuzemko in 1994. According to this hypothesis, Emilia's fatal ... Kubba and Young pointed out a number of other conceivable, if unlikely, diagnoses, besides cystic fibrosis and alpha 1- ... secondary to liver cirrhosis in the course of alpha 1-antitrypsin deficiency. Frédéric's symptoms of liver insufficiency would ... 44 (1): 77-84. PMID 12590184. Kubba, AK; Young, M (1998). "The long suffering of Frederic Chopin". Chest. 113 (1): 210-6. doi: ...

*Hepatitis

In alpha-1-antitrypsin deficiency, a co-dominant mutation in the gene for alpha-1-antitrypsin results in the abnormal ... Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis. Similar to hepatitis A, ... When the liver is involved, alpha-1-antitrypsin deficiency and Wilson's disease tend to present as hepatitis in the neonatal ... There have been 7 drug treatments approved to date in the United States: Injectable interferon alpha was the first therapy ...

*Haptoglobin

... comparison of complementary DNA encoding Hp alpha 1S and Hp alpha 2FS". Nucleic Acids Res. 12 (11): 4531-8. doi:10.1093/nar/ ... "Characterization of human haptoglobin cDNAs coding for alpha 2FS beta and alpha 1S beta variants". FEBS Lett. 168 (1): 103-7. ... This gene encodes a preproprotein that is processed to yield both alpha and beta chains, which subsequently combines as a ... van der Straten A, Falque JC, Loriau R, Bollen A, Cabezón T (1986). "Expression of cloned human haptoglobin and alpha 1- ...

*Reference ranges for blood tests

"Alpha-1 antitrypsin deficiency: an overlooked cause of late hemorrhagic disease of the newborn". Journal of Pediatric ... Last revised 1/15/2013 Derived from mass values using molar mass of 90.08 g/mol Derived from mass values using molar mass of ... 1, 1999 (stating 1.9-3.3 g/L) Derived by dividing mass values with molar mass Ferritin by: Mark Levin, MD, Hematologist and ... Derived from molar values using molar mass of 22.99 g•mol−1 Derived from molar values using molar mass of 39.10 g•mol−1 MERCK ...

*Myeong-Hee Yu

Much of Yu's work has focused on unlocking the structure and folding of the protein alpha-1 antitrypsin, which is a serpin ... Yu, Myeong-Hee; Lee, Kee Nyung; Kim, Jeongho (1995-05-01). "The Z type variation of human α1-antitrypsin causes a protein ... She has also patented the alpha-1 antritrypsin mutein with a disulfide bond and the method for preparing it along with her ... "Single amino acid substitutions of alpha 1-antitrypsin that confer enhancement in thermal stability". The Journal of Biological ...

*Progressive disease

Lungs: Emphysema due to alpha-1 antitrypsin deficiency is a slowly progressive pulmonary disease. Kidneys: Goodpasture's ... Pancreas: Type 1 diabetes mellitus involves rapidly progressive loss of insulin secretory capacity compared to type 2 diabetes ...

*Serpin

Owen MC, Brennan SO, Lewis JH, Carrell RW (September 1983). "Mutation of antitrypsin to antithrombin. alpha 1-antitrypsin ... Well-characterised serpinopathies include α1-antitrypsin deficiency (alpha-1), which may cause familial emphysema and sometimes ... For example, the Antitrypsin-Pittsburgh mutation (M358R) causes the α1-antitrypsin serpin to inhibit thrombin, causing a ... Antitrypsin augmentation therapy is approved for severe antitrypsin deficiency-related pulmonary emphysema. In this therapy, ...

*Granulomatous mastitis

Alpha 1-antitrypsin deficiency was documented in one case, interferon-alpha therapy in another case. Similar cases of ... Shaaban, H.; Slim, J.; Choo, H. (2012). "Idiopathic granulomatous mastitis as a complication of interferon-alpha therapy". ... 18 (1): 27-36. PMID 9157401. Lai, E. C. H.; Chan, W. C.; Ma, T. K. F.; Tang, A. P. Y.; Poon, C. S. P.; Leong, H. T. (2005). " ... 11 (1): 73. doi:10.1111/j.1075-122X.2005.21404.x. PMID 15647084. Goldberg, J.; Baute, L.; Storey, L.; Park, P. (2000). " ...

*Heparin cofactor II

This protein shares homology with antithrombin and other members of the alpha 1-antitrypsin superfamily. Mutations in this gene ... 88 (1): 89-97. PMID 12152684. Hayakawa Y, Hirashima Y, Kurimoto M, et al. (2002). "Contribution of basic residues of the A ... 61 (1): 111-118. Pizzo SV (1989). "Serpin receptor 1: a hepatic receptor that mediates the clearance of antithrombin III- ... 522 (1-3): 147-50. doi:10.1016/S0014-5793(02)02930-7. PMID 12095635. Mitchell JW, Church FC (2002). "Aspartic acid residues 72 ...

*SERPINB10

Serpins are characterized by a well-conserved tertiary structure that consists of 3 beta sheets and 8 or 9 alpha helices. A ... Schleef RR, Chuang TL (August 2000). "Protease inhibitor 10 inhibits tumor necrosis factor alpha -induced cell death. Evidence ... "Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins". Biochemistry. 28 ... doi:10.1007/s10038-005-0285-1. PMID 16172807. Riewald M, Schleef RR (November 1995). "Molecular cloning of bomapin (protease ...

*CDIPT

2005). "Alpha-1 antitrypsin deficiency in Italy: regional differences of the PIS and PIZ deficiency alleles". Monaldi Archives ... 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97 ... 138 (1-2): 171-4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). " ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). " ...

*AMFR

"Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of alpha-1-antitrypsin". Biochem. ... 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Registre M, Goetz JG, St Pierre P, et al. (2004). "The gene product of the ... Song BL, Sever N, DeBose-Boyd RA (2005). "Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples ...

*SERPINA2

Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2 is a protein that in humans is encoded by ... antitrypsin like gene it was discovered that SERPINA2 did not have any promoter but did contain substantial homology to ... Rollini P, Fournier RE (December 1997). "Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin ... antitrypsin), member 2". Retrieved 2017-09-21. Hofker MH, Nelen M, Klasen EC, Nukiwa T, Curiel D, Crystal RG, Frants RR ( ...

*Dutch hypothesis

... involving alpha 1-antitrypsin overexpression and consequent alpha-1 proteinase deficiency), the British hypothesis (regarding a ... ISBN 978-1-119-96373-8. Retrieved 15 November 2012. Richard A. King; Jerome I. Rotter; Arno G. Motulsky (17 October 2002). The ...

*Variegate porphyria

July 1988). "Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14". Hum. ... ISBN 1-4160-2999-0. This article incorporates public domain text from The U.S. National Library of Medicine Variegate porphyria ... In Finland, the prevalence is approximately 1 in 75.000. When it does occur in other populations (such as Switzerland), it can ... ISBN 978-1-4051-3400-2. Mustajoki, P. (1980). "Variegate porphyria. Twelve years' experience in Finland". The Quarterly journal ...
Alpha-1 antitrypsin - MedHelps Alpha-1 antitrypsin Center for Information, Symptoms, Resources, Treatments and Tools for Alpha-1 antitrypsin. Find Alpha-1 antitrypsin information, treatments for Alpha-1 antitrypsin and Alpha-1 antitrypsin symptoms.
116 161. Aldonyte R, Jansson L, Ljungberg O, Larsson S, Janciauskiene S. Polymerized alpha(1) antitrypsin is present on lung vascular endothelium. New insights int o the biological significance of alpha(1) antitrypsin polymerization. Histopathology 2004;45:587592. 162. Wang RL, McLaughlin T, Cossette T, Tang Q, Foust K, Campbell Thompson M, Martino A, et al. Recombinant AAV Serotype and Capsid Mutant Comparison for Pulmonary Gene Transfer of alpha1 Antitrypsin Using Invasive and Noninvasive Delivery. Molecular Therapy 2009;17:8187. 163. Carlson JA, Rogers BB, Sifers RN, Finegold MJ, Clift SM, DeMayo FJ, Bullock DW, et al. Accumulation of PiZ alpha 1antitrypsin causes liver damage in transgenic mice. J Clin Invest 1989;83:11831190. 164. Sifers RN, Rogers BB, Hawkins HK, Finegold MJ, Woo SL. Elevated synthesis of human alpha 1antitrypsin hinders the secretion of murine alpha 1antitrypsin from hepatocytes of transg enic mice. J Biol Chem 1989;264:1569615700. 165. Kang Y, Stein CS, Heth JA, Sinn PL, ...
QIU-LING, Li et al. Association of polymorphism of the alpha 1-antitrypsin gene with milk production traits in Chinese Holstein. S. Afr. j. anim. sci. [online]. 2010, vol.40, n.2. ISSN 2221-4062.. Protein degradation in bovine milk affects the quality of dairy products. Alpha 1-antitrypsin (AAT) can protect vulnerable elastic tissues from degradation by neutrophil elastase. The aim of this study was to assess the association of polymorphisms in bovine AAT gene with milk yield and milk composition in Chinese Holstein. Traits analyzed were fat percentage, protein percentage, 305-day milk yield and somatic cell score (SCS). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-polymerase chain reaction (CRS-PCR) and allele specific-polymerase chain reaction (AS-PCR) methods were used to genotype five loci in coding regions of the sequence, including position 5504, 5609, 5624, 5747 and 8178 in Chinese Holstein. The five mutations were all silent ...
Alpha-1-antitrypsin or α1-antitrypsin (A1AT, A1A, or AAT) is a protein belonging to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. A protease inhibitor, it is also known as alpha1-proteinase inhibitor (A1PI) or alpha1-antiproteinase (A1AP) because it inhibits various proteases (not just trypsin). In older biomedical literature it was sometimes called serum trypsin inhibitor (STI, dated terminology), because its capability as a trypsin inhibitor was a salient feature of its early study. As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase, and has a reference range in blood of 0.9-2.3 g/L (in the US the reference range is expressed as mg/dL or micromoles), but the concentration can rise manyfold upon acute inflammation. 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, ...
TY - JOUR. T1 - Intrapleural administration of a serotype 5 adeno-associated virus coding for α1-antitrypsin mediates persistent, high lung and serum levels of α1-antitrypsin. AU - De, Bishnu. AU - Heguy, Adriana. AU - Leopold, Philip L.. AU - Wasif, Nabil. AU - Korst, Robert J.. AU - Hackett, Neil R.. AU - Crystal, Ronald. PY - 2004/12/1. Y1 - 2004/12/1. N2 - α1-Antitrypsin (α1AT) is a serine proteinase inhibitor that protects the lung from degradation by neutrophil proteases. In α1AT deficiency, an autosomal recessive disorder resulting from mutations in the α1AT (approved symbol SERPINA1) gene, serum α1AT levels of ,570 μg/ml are associated with development of emphysema. Adeno-associated virus (AAV) serotype 2 (AAV2) vectors expressing α1AT administered intramuscularly or intravenously mediate sustained serum levels of α1AT in experimental animals. Since the lung is only 2% of the body weight, AAV vector delivery to the muscle or liver is inefficient, as most of the α1AT does not ...
Black Swan Analysis Epiomic Epidemiology Series Forecast Report on Alpha-1 Anti-Trypsin in 9 Major Markets Alpha-1 Anti-Trypsin (AAT) is an enzyme belonging to the serpin super
Alpha-1 antitrypsin (AAT) is a protein that protects the lungs from damage caused by activated enzymes. Alpha-1 antitrypsin tests help diagnose alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin (AAT) is a protein that protects the lungs from damage caused by activated enzymes. Alpha-1 antitrypsin tests help diagnose alpha-1 antitrypsin deficiency.
alpha 1 Antitrypsin antibody (HRP) (serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1) for ELISA. Anti-alpha 1 Antitrypsin pAb (GTX74131) is tested in Human samples. 100% Ab-Assurance.
alpha 1 Antitrypsin antibody [8C7] (serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1) for WB. Anti-alpha 1 Antitrypsin mAb (GTX52992) is tested in Human samples. 100% Ab-Assurance.
The Alpha-1-Antitrypsin (α1-AT) IEF gel kit is intended for the identification of genetic variants in human serum by a combination of iso-electric focusing and immunofixation. The Alpha-1- Antitrypsin variants are separated according to iso- electric point in an agarose IEF gel.. ...
Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase in serum AAT levels with the same dose of AAV gene therapy vector and allow for increased volume and thereby dose of vector. In macaques, similar serum myc-tagged rhAAT was produced using regional venous infusion when compared to direct IM delivery at the same total vg dose with either rAAV1 or
Alpha1-antitrypsin molecule. Computer model showing the structure of alpha1-antitrypsin (blue-green) with its reactive loop (pink). This protein, also known as alpha-1 proteinase inhibitor, is a type of serine protease inhibitor (serpin) and is named after its ability to covalently bind and irreversibly inactivate serine proteases, including the digestive enzyme trypsin. It plays a key role in mediating inflammation and a deficiency results in the lung disease emphysema. - Stock Image C035/5538
A protease/anti-protease imbalance is a characteristic feature of inflammatory lung diseases such as cystic fibrosis (CF) and COPD. However, alpha-1-antitrypsin (AAT) enzyme replace- ment therapy (ERT) trials have not shown conclusive evidence of therapeutic benefit. Here, we assessed whether transduction of murine lungs with a pseudotyped SIV vector, rSIV.F/HN-hCEF-AAT, generates therapeutic levels of AAT. Mice were transduced with rSIV.F/HN-hCEF-AAT (1.4e8 TU/mouse) by nasal instillation and culled 10 days post-trans- duction. AAT levels in lung homogenate and epithelial lining fluid (ELF) were 3 logs above controls (p | 0.05), and hAAT concentration in ELF was 92-28lg/ml, similar to the thera- peutic AAT level in ELF of 70lg/ml. For comparison trans- fection of mouse lung with cationic lipid GL67A complexed to hCEFI-AAT only led to 0.4-0.1lg/ml AAT in ELF. A neutrophil elastase (NE) activity assay showed that the recombinant AAT successfully neutralised NE activity (p | 0.05). In a separate
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α1-antitrypsin (AAT) is one of the major serine proteinase inhibitors in human plasma, synthesised primarily in the liver, but also in extra-hepatic tissues and cells, including neutrophils, monocytes and alveolar macrophages [1-4]. Under normal conditions the daily production of AAT is 34 mg per kg body weight. The average concentration of AAT in plasma in healthy individuals is estimated to be 1.3 mg/ml, with a half-life of 3 to 5 days [5]. The concentration of AAT during acute phase processes rises by three- to fourfold above normal while, for example, local levels of AAT are shown to increase up to 11-fold [4]. The concentration of AAT in plasma also increases during oral contraceptive therapy and pregnancy [6]. A large number of studies has proven the importance of this rapid and high magnitude increase in AAT concentrations for the local regulation of serine proteinase activity and tissue protection against proteolytic destruction [7, 8]. AAT/proteinase complex formation and inhibitor ...
Press Release issued Jul 9, 2014: The present Competitive Intelligence Report about alpha1-proteinase inhibitors (alpha1-PI), alpha1-antitrypsin (AAT) and elastase inhibitors provides a competitor evaluation in the field of human plasma-derived, recombinant, transgenic, synthetic and gene therapeutic approaches for treatment of lung emphysema caused by congenital deficiency and of other diseaes by synthetic elastase inhibitors or RNA approaches as of July 2014. Purchase of the downloadable pdf report includes a 6-month online access to the data of the report and any updates since the publication date. Credentials to access the database will be sent by e-mail and allow online work with the project data to print or export an individual report.
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The AAT gene contains at least two enhancer elements , one at the 5 end of the gene and the other at the 3 end. The 5 enhancer is dominant under basal conditions and, following stimulation with IL-6 and related cytokines, both enhancers are essential and the 3 enhancer plays a major role.. Interferon γ and transforming growth factor β also modulate the hepatocyte response to IL-6. In addition to cytokines having an effect on AAT gene regulation, dexamethasone and oestrogen may have a stimulatory effect on gene regulation.. Monocyte AAT production appears to be primarily under the control of IL-6, although lipopolysaccharide , interleukin-1β (IL-1β) and tumour necrosis factor α (TNFα) all cause a 2±3-fold increase in AAT production by peripheral blood monocytes.. ...
The study was a Phase 1B/2A, uncontrolled, open-label, single-center study in individuals with congenital AAT (alpha 1-antitrypsin) deficiency. A baseline bronchoscopy with bronchoalveolar lavage (BAL) was performed 3 to a maximum of 4 weeks prior to the first administration of study drug. Fifteen eligible subjects were randomized to receive 1 of 3 dosing regimens of rAAT (100 mg daily, 100 mg twice daily, or 200 mg daily) administered via nebulization for 7 consecutive days. A post-treatment nadir BAL was obtained on study Day 8 (12 hours after last dose for subjects who receive drug therapy twice daily and 24 hours after the last dose for subjects who receive study product daily). BALs were conducted in the same lung lobe/segment. Follow-up visits took place on Day 15 and Day 36 ...
Recent research and the current scenario as well as future market potential of Global Alpha 1-Antitrypsin (AAT) Replacement Therapy Market: Size, Trends...
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This trial is investigating the efficacy of alpha 1-antitrypsin [Zemaira] in patients with steroid refractory graft-versus-host disease.
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Alpha-1-Antitrypsin Antibody 16382-1-AP has been identified with ELISA, FC, IHC, IP, WB. 16382-1-AP detected 47 kDa band in mouse kidney tissue with 1:500-1:2000 dilution...
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Rabbit polyclonal alpha 1 Antitrypsin antibody validated for IHC and tested in Human, Hrs, Mink, Mk and Bb. Immunogen corresponding to full length native…
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Serpina3n: latus, stain with aniline oil gential violet, steaming. serpina3n mouse (lus diseases, other than typhoid fever, in which he
More than 40 phenotypes of AAT exist. The inherited deficiency, seen most often as the ZZ, SS and SZ phenotypes, is associated with neonatal hepatitis and infantile cirrhosis. In adults, these phenotypes are associated with chronic lung disease, including emphysema and chronic bronchitis.
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Альфа-1-антитрипсин - белок (гликопротеин), синтезируемый в печени, моноцитах, макрофагах, клетках слизистой оболочки кишечника. Он служит ингибитором большинства протеолитических ферментов, имеющих в составе своего активного участка аминокислоту серин (трипсина, хемотрипсина, эластазы, калликреина, катепсинов и других ферментов тканевых протеаз). Важнейшая физиологическая роль альфа-1-антитрипсина по-видимому состоит в торможении протеаз, особенно эластаз, выделяющихся из лейкоцитов при фагоцитозе. Имея небольшой размер молекулы, он легко ...
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BioAssay record AID 36627 submitted by ChEMBL: Agonism of human alpha-1A adrenergic receptor expressed in rat 1 fibroblast cells.
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Health,New research shows a molecule that stops the growth of the AIDS virus in the blood may also inhibit the growth of other viruses.// Researchers say alpha-1 antitrypsin (AAT) -- a protein in the blood -- deactivates cells stopping viruses from multiplying. In order for cells to grow they must be in an active state. They say the concept is
Up-regulation of blood derived protein fragments in urine samples of the PREDICTIONS cohort.Displayed is the regulation of alpha-1-antitrypsin fragments, an alp
Representative macrographs (A, B) and light micrographs (C, D) of hearts from the diabetic rats. The diabetic rats kept under normoxia exhibited nearly normal m
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Browse drugs and medications alphabetically (Professional). Includes Aloxi, Aloxi Capsules, Alpha Pro Dental Gel, Alpha-hydroxy, Alpha1-Proteinase Inhibitor
Research Corridor has published a new research study titled "Alpha 1-Antitrypsin Deficiency Treatment Market - Growth, Share, Opportunities, Competitive Analysis and Forecast, 2017 - 2025". The Alpha 1-Antitrypsin Deficiency Treatment Market report studies current as well as future aspects of the Alpha 1-Antitrypsin Deficiency Treatment Market based upon factors such as market dynamics, key ongoing trends and segmentation analysis. Apart from the above elements, the Alpha 1-Antitrypsin Deficiency Treatment Market research report provides a 360-degree view of the Lipstick Packing industry with geographic segmentation, statistical forecast and the competitive landscape.. Browse the complete report at http://www.researchcorridor.com/alpha-1-antitrypsin-deficiency-treatment-market/. Geographically, the Alpha 1-Antitrypsin Deficiency Treatment Market report comprises dedicated sections centering on the regional market revenue and trends. The Alpha 1-Antitrypsin Deficiency Treatment Market has been ...
Global Markets Directs, Alpha- Antitrypsin Deficiency - Pipeline Review, H1 2012, provides an overview of the Alpha- Antitrypsin Deficiency therapeutic pipeline. This report provides information on the therapeutic development for Alpha- Antitrypsin Deficiency, complete with latest updates, and special features on late-stage and discontinued projects. It also reviews key players involved in the therapeutic development for Alpha- Antitrypsin Deficiency. Alpha- Antitrypsin Deficiency - Pipeline Review, H1 2012 is built using data and information sourced from Global Markets Directs proprietary databases, Company/University websites, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources, put together by Global Markets Directs team.
Background Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease (chronic obstructive pulmonary disease or COPD, which is a chronic lung condition that prevents the air supply from getting to the lungs). It affects about 1 in 1600 to 1 in 5000 people. Patients with lung disease suffer from shortness of breath, reduced ability to exercise and wheezing. People who smoke are more seriously affected and have a greater risk of dying from the disease.. Study characteristics 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. We found three randomised clinical trials (283 participants in the analyses) comparing treatment with alpha-1 antitrypsin with placebo (a pretend treatment) for two to three years. All participants were ex-smokers or had never smoked but had the genetic problem that carried a high risk of developing lung problems. The evidence is ...
TY - JOUR. T1 - Serum alpha-2-macroglobulin, antitrypsin and antichymotrypsin activities in patients receiving treatment with cyclosporine. AU - Roche, Maya. AU - Kusumanjali, G.. AU - Chinnapu Reddy, G.. AU - Kanagasabhapathy, A. S.. AU - Rao, Pragna. PY - 2006. Y1 - 2006. N2 - Cyclosporine has been reported to function as an inhibitor of the chymotrypsin like activity of proteasome. We hypothesized that the administration of an exogenous proteinase inhibitor may affect the activities of the naturally occurring serum anti proteinases. The aim of this study was to observe the pattern of alteration of serum alpha 2 macroglobulin (AMG), alpha 1- antitrypsin (AT) and alpha 1-antichymotrypsin (ACT) activities in renal transplant patients receiving the immunosuppressive drug, cyclosporine. Patients (97) who had received a single renal allograft were inducted into the study. Subjects were on a twice-daily dosage of cyclosporine capsules. Trough (Co) and two-hour post dose (C 2) cyclosporine levels ...
Blancos Overview of Alpha-1 Antitrypsin Deficiency: History, Biology, Pathophysiology, Related Diseases, Diagnosis, and Treatment is a robust introduction to topics associated with Alpha-1 Antitrypsin Deficiency (AATD). Included are topics ranging from the history of the disease, biology, pathophysiology, related diseases, including the two major manifestations of the disease (liver disease and lung disease), and diagnosis and treatment.. The book addresses the need for the amalgamation of current and novel concepts and practices in the field of AATD. AATD is under-recognized in the medical community and, as a result, it is underdiagnosed. The book provides increased awareness and understanding of the condition to improve diagnosis rates and enhance patient care. This book is an essential tool and reference, beneficial to clinicians who screen and treat AATD patients, as well as research scientists working in the AATD field at junior and senior levels.. ...
Please refer to the alpha 1-antitrypsin for the various protease inhibitor (Pi) genotypes and phenotypes. Normally, alpha 1-antitrypsin is produced in the liver and exists in levels of 1.5-3.5 gram/litre. When the levels are reduced (40-60%, in the PiSS, PiMZ and PiSZ phenotypes), most people will only suffer symptoms if they smoke, as the levels are still sufficient to counteract "normal" elastase activity in inflammation. Only in the PiZZ phenotype, when the levels are less than 15%, emphysema develops at a young age, and 50% will develop liver cirrhosis due to the accumulated protein, which is not secreted properly. On liver biopsy, they show as PAS-positive, diastase-negative granules. Apart from increasing the inflammatory reaction in the airways, cigarette smoke also directly inactivates alpha 1-antitrypsin by oxidizing essential methionine residues to sulfoxide forms, decreasing the enzyme activity by a rate of 2000. ...
Alpha 1-antitrypsin deficiency is a genetic disorder caused by defective production of alpha 1-antitrypsin (AAT). Gene therapy approaches have been conducted in patients with AAT deficiency with successful AAT expression, but not to the therapeutic levels required to reduce the risk of emphysema. Codon optimization, a somewhat new and evolving technique, is used by many scientists to maximize protein expression in living organisms by altering translational and transcriptional efficiency as well as protein refolding. The purpose of this study was to develop single stranded and double stranded AAT gene constructs, test their protein expression in vitro, and compare with those levels expressed by the AAT construct that is currently in clinical trials. Three constructs were to be developed, yet only one construct was successfully cloned. This clone, optimized ds-CB-AAT, illustrated increased AAT protein expression as the transfection time increased. However, protein levels were appreciably lower in
... Grifols Canada has partnered with Innomar Strategies Inc to provide the Prolastin Direct® Program, a confidential service specially created to assist Canadian physicians and their patients who may be candidates for augmentation therapy with Prolastin®-C (Alpha1-Proteinase Inhibitor [Human]).. When a physician makes a referral to the Prolastin Direct program, a trained reimbursement specialist will conduct a thorough review of all public and private reimbursement options for Prolastin-C on behalf of each patient. Once the review is complete, the patient and the referring physician will be provided with options available for reimbursement.. If a decision is made to begin augmentation therapy with Prolastin-C, Prolastin Direct will work with the patient, the physician, the pharmacy and the Innomar network of clinics and nurses to initiate therapy. Prolastin Direct staff can help coordinate schedules and other arrangements with all parties so the patient can receive his or her ...
Alpha 1-antitrypsin deficiency is an inherited disorder that can cause lung disease in adults and liver disease in adults and children. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs. The liver usually makes the protein, and releases it into the bloodstream. Because of a mutation in the SERPINA1 gene, some people have little or no AAT. Not having enough AAT may lead to emphysema or liver problems. Smoking increases the risk. A deficiency of AAT can be treated but not cured. One treatment involves adding to or replacing the missing protein. More severe cases may require a lung transplant. This condition is caused by mutations in the SERPINA1 gene and inherited in an autosomal co-dominant fashion ...
PASADENA, Calif.-(BUSINESS WIRE)- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that it has initiated dosing in a Phase 1 clinical trial of ARC-AAT, the companys candidate for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disorder that severely damages the liver and lungs of affected individuals. Trial initiation followed successful completion of the Clinical Trial Notification (CTN) regulatory process in Australia. The study will be conducted in two parts, with Part A in healthy volunteers and Part B in patients with AATD. The primary objectives of the study are to determine the safety and tolerability of escalating doses of ARC-AAT, evaluate the pharmacokinetics, and determine the effect on circulating levels of alpha-1 antitrypsin. Initial data from this study is expected in late 2015.. Click here to read the full release. ...
The AATD is a metabolic disorder that predisposes the affected individual to chronic pulmonary disease, in addition to chronic liver disease, cirrhosis, and hepatocellular carcinoma. Clinical manifestations are always present in patients with complete absence of serum alpha-1 antitrypsin (null variants). The majority of patients with ZZ or SZ genotypes, and some others with the SS genotype, have pulmonary or hepatic symptoms. Severe lung and liver disease are rarely observed in the same person. Heterozygous individuals, with both a normal and a variant allele (MZ or MS), rarely develop clinical symptoms. In most patients with symptomatic AATD, the dominant manifestation is lung disease: the symptoms appear earlier and may proceed faster if additional risk factors are present, like smoke or air pollutants. The mean life expectancy of homozygous patients (ZZ and SS variant) is from 48 to 52 years for smokers and from 60 to 68 years for nonsmokers. Severe pulmonary impairment, manifesting as COPD ...
Anti-neutrophil-elastase defenses of the lower respiratory tract in α1-antitrypsin deficiency directly augmented with an aerosol of α1-antitrypsin Academic Article ...
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. METHODS: We present data from the first 3,000 individuals screened following ATS/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. RESULTS: The Irish National
article{28d5c2ad-b244-4d8a-b7d9-b8f6b4fb3b95, abstract = {,p,Severe alpha-1-antitrypsin (AAT) deficiency (PiZZ) is a risk factor for liver disease, but the prevalence of liver cirrhosis and hepatocellular cancer in PiZZ adults is unknown. The risk of liver disease in adults with moderate AAT deficiency (PiSZ) is also unknown. A cohort of 127 PiZZ, 2 PiZnull, 54 PiSZ, and 1 PiSnull individuals were identified by the Swedish national neonatal AAT screening program between 1972 and 1974, when all 200, 000 newborn infants in Sweden were screened for AAT deficiency. The cohort has been followed up since birth. Our aim was to study liver function and signs of liver disease in this cohort at 37 to 40 years of age in comparison with a matched, random sample of control subjects identified from the population registry. Eighty seven PiZZ, 32 PiSZ, and 92 control subjects (PiMM) answered a questionnaire on medication and alcohol consumption and provided blood samples. Liver stiffness was assessed by ...
article{23bc97b5-44c3-44d9-8ce7-616d5254f6f0, abstract = {Background: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT) might be superior to pulmonary function tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of 32 years. Methods: A subgroup of PiZZ and PiSZ individuals identified during the Swedish newborn screening programme in 1972-74 underwent multi-slice CT and PFT at the age of 32 years. From the CT scans the percentile density at 15% (PD15) and the relative area below -910 Hounsfield Units (RA(-910) HU) were calculated. The results of PFT and CT were compared between the AAT-deficient individuals and an age-matched control group. Results: Twenty-five PiZZ, 11 PiSZ and 17 PiMM individuals participated in the study. All Pi subgroups had normal lung function. The mean PD15 was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in ...
article{8610527, abstract = {Despite recent improvements, α1-antitrypsin deficiency (AATD) remains a rarely diagnosed and treated condition. To assess the variability of AATD diagnosis/treatment in Europe, and to evaluate clinicians views on methods to optimise management, specialist AATD clinicians were invited to complete a web-based survey. Surveys were completed by 15 physicians from 14 centres in 13 European countries. All respondents perceived the AATD diagnosis rate to be low in their country; 77% of physicians believed that ∼15% of cases were diagnosed. Low awareness was perceived as the greatest barrier to diagnosis. Spirometry was considered more practical than quantitative computed tomography (QCT) for monitoring AATD patients in clinical practice; QCT was considered more useful in trials. AAT therapy provision was reported to be highly variable: France and Germany were reported to treat the highest proportion (∼60%) of diagnosed patients, in contrast to the UK and Hungary, ...
Introduction Alpha-1 antitrypsin deficiency (AATD) is a genetic condition associated with COPD; patients homozygous for the mutant Z allele (PiZZ) are predisposed to severe, early-onset emphysema of the lung, and also progressive fibrosis and cirrhosis of the liver. There is a well-known association between COPD and cardiovascular disease, with around 1 in 3 COPD deaths attributed to a cardiac cause.1 We hypothesised that cardiovascular risk in AATD may be independently modified by the severity of lung and liver disease, through common or related pathophysiological processes. ...
Alpha1-antitrypsin deficiency (AATD) was first described by Laurell and Eriksson in 1963. Laurell noted the absence of the band of alpha1- protein in 5 of 1500 serum protein electrophoreses (SPEP) submitted to his laboratory in Sweden.
Alpha-1 antitrypsin (A1AT) deficiency is a common inherited condition caused by a lack of a protease inhibitor (Pi) normally produced by the liver. The role of A1AT is to protect cells from enzymes such as neutrophil elastase.. ...
Alpha 1 Antitrypsin Deficiency Clinical Research Trial Listings in Gastroenterology Pulmonary/Respiratory Diseases Hepatology (Liver, Pancreatic, Gall Bladder) on CenterWatch
OBJECTIVE: To investigate the severity of bronchiectasis and associated emphysema and the correlation with phenotype in patients with Alpha-1 antitrypsin deficiency. METHODS: The scoring system of Ooi and his colleagues for bronchiectasis was modifie
Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The measurement of forced expiratory volume in 1 second (FEV1) and its decline over time are prognostic indicators of early chronic airflow obstruction. Although alpha1-antitrypsin (AAT) deficiency (Z allele) was shown to be a risk factor for rapid decline in lung function, individuals with the same AAT genotype may differ in their phenotypes suggesting the presence of other genetic modifiers. Mat
References for Abcams Anti-Trypsin Inhibitor antibody (ab34819). Please let us know if you have used this product in your publication
In Response:. We appreciate the comments raised by Dahl et al in the letter above. However, there are a number of differences in the study design reported in our article published in Arteriosclerosis, Thrombosis, and Vascular Biology1 and that of both Dahl et al2 and Elzouki et al,3 which could have led to discrepancies in the concluded role for alpha-1-antitrypsin (AAT). While our study examined the association of common and rare AAT variants with progression of atherosclerosis in individuals with well defined atherosclerotic disease, the others looked at the occurrence of ischemic heart disease (IHD) or ischemic cerebrovascular disease (ICVD) in individuals who carried rare AAT deficiency genotypes compared with controls. Atherosclerosis progression, IHD, and ICVD are very different disease endpoints, and furthermore, the causes of ischemia are multiple.4 In addition, while our study is a prospective analysis of angiographically defined disease, the other two are case:control analyses. So the ...
TY - JOUR. T1 - Amyloid-β peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor. AU - Joslin, Gregg. AU - Krause, James E.. AU - Hershey, Andrew D.. AU - Adams, Steven P.. AU - Fallon, Robert. AU - Perlmutter, David H.. PY - 1991. Y1 - 1991. N2 - During the formation of an inhibitory complex with neutrophil elastase, α1 antitrypsin (α1 AT) undergoes a structural rearrangement and the resulting α1 AT-elastase complex becomes endowed with chemoattractant activities, mediates an increase in synthesis of α1 AT, and is rapidly cleared from the circulation. In previous studies we have provided evidence that these biological activities involve the recognition of a conformation-specific domain in the α1 AT molecule by a cell surface receptor on human hepatoma HepG2 cells and human monocytes. The receptor has been termed the serpin-enzyme complex (SEC) receptor because it also recognizes complexes of serpins antithrombin III, α1 anti-chymotrypsin, and C1 inhibitor with ...
A deficiency of the enzyme alpha 1-antitrypsin results in low levels or a lack of an essential blood protein that protects tissues in the lungs from being destroyed by enzymes released from the bodys own white blood cells.
GAINESVILLE, Fla. and CAMBRIDGE, Mass. and PHILADELPHIA, Jan. 20, 2016-- Applied Genetic Technologies Corporation, a biotechnology company conducting human clinical trials of adeno-associated virus- based gene therapies for the treatment of rare diseases, today announced data evaluating the use of recombinant AAV-AAT vector gene delivery to muscle in...
Alpha‐1‐antitrypsin deficiency is one of the morecommon metabolic disorders, and is usually associated with one common gene mutation
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow limitation that is progressive and associated with an enhanced chronic inflammatory response in the lung to noxious particles or gases. Deficiency of alpha-1 antitrypsin (AAT) is the best-studied genetic risk factor for COPD and one of the most common genetic disorders among Caucasians. The availability of specific therapy for AATD makes it possible to improve outcomes, but however, AATD is underrecognized and undertreated. This program will discuss diagnosis and treatment options for patients with COPD and AATD, with the most recent recommendations from the GOLD 2017 report.. This webcast was recorded live and is being used with the permission of the presenters.. Learning Objective(s): ...
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Chemical chaperones and low growth temperature are often used as a first step to evaluate the feasibility of treatments using pharmacological chaperones for secretion-impaired mutations. In this context, the examples of the CFTR ΔF508 or α1-antitrypsin Z variants responsible for cystic fibrosis and α1-antitrypsin deficiency, respectively, are promising.16-18 In our transfected cell model we found that none of the chemical chaperones used (4-PBA, DMSO and TMAO) restored the secretion of the fibrinogen mutants studied. By contrast, low-temperature incubation (27°C) allowed partial secretion of the Bβ p.G444S (p.G414S) and γ p.W253C (p.W227C) mutants. Low temperature may act kinetically by slowing down the folding process thus allowing a higher amount of mutant proteins to adopt a suitable conformation and reach their final destination.17 Interestingly, in this condition, the two nonsense mutants Bβ p.W467X (p.W437X) and Bβ p.R485X (p.W455X) were not secreted. This suggests a more severe ...
Alpha-1 antitrypsin (AAT) is an inhibitor of neutrophil elastase and a member of the serine proteinase inhibitor (serpin) superfamily, and little is known about its activity in sickle cell disease (SCD). We hypothesize that AAT may undergo changes in SCD because of the high oxidative stress and inflammation associated with the disease. We have found high AAT levels in SCD patients compared to controls, while mutant genotypes of SERPINA1 gene had decreased AAT levels, in both groups. AAT showed negative correlation with red blood cells, hemoglobin (Hb), hematocrit, high-density lipoprotein cholesterol, urea, creatinine, and albumin and was positively correlated with mean corpuscular Hb concentration, white blood cells, neutrophils, Hb S, bilirubin, lactate dehydrogenase, ferritin, and C-reactive protein ...
My laboratory research to date has focused on using lentiviruses to develop a gene therapy for alpha-1 antitrypsin deficiency. I have approached this problem through the manipulation of two target cell populations: hematopoietic stem cells and alveolar macrophages. Both approaches have resulted in long-term expression of human alpha-1 antitrypsin in laboratory animals. In addition to the in-vivo overexpression of alpha-1 antitrypsin, I am interested in manipulating other genes which may play a role in the pathogenesis of COPD, such as NF-kB.. A second area of interest is embryonic stem cell biology. I am working with Darrell Kotton and others in our division to study the progression of definitive endoderm to lung epithelium.. ...
Deterioration of quality of life is associated with the exacerbation frequency in individuals with alpha-1-antitrypsin deficiency â analysis from the German Registry Nikolas Bernhard,1 Philipp M Lepper,1 Claus Vogelmeier,2 Martina Seibert,1 Stefan Wagenpfeil,3 Robert Bals,1 Sebastian Fähndrich1 1Department of Internal Medicine V â Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, 2Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), 3Faculty of Medicine, Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Campus Homburg, Germany Background: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary disease that is associated with a higher risk to develop chronic obstructive pulmonary disease and liver cirrhosis. Previous cross-sectional studies on AATD individuals have shown a
Abrasion: area where skin or other tissue is scraped away. Absorb: Take up fluids, take in. Absorption: the way a drug or other substance enters the body. Acidosis: Condition when blood contains more acid than normal. Acoumeter: tool used to measure hearing. Acuity: Clearness, keenness, especially of vision - airways. Acute: New, recent, sudden. Adenopathy: Swollen lymph nodes (glands). Adhesion: tissue stuck together. Adjuvant treatment: Added treatment. Adjuvant: Helpful, assisting, aiding. Adrenal gland: gland found over each kidney. Adverse Effect: Unwanted effect. Albuminuria: protein in the urine. Allergen: A substance that gets into the body and activates the immune system, which produces an allergic reaction.. Allergic Reaction: Rash, trouble breathing. Allergy: oversensitivity to a substance. Alpha1-antitrypsin deficiency: Alpha-1 antitrypsin is a protein that is made in the liver. The liver releases this protein into the bloodstream. Alpha-1 antitrypsin protects the lungs so they can ...
Damage to airways occurs as follows: Irritants cause inflammation of the alveoli (tiny air sacs of the lung). If such inflammation is long standing, permanent damage may result. As a result of the irritation, white blood cells collect in the inflamed alveoli and release enzymes called neutrophil elastase that damage connective tissue in the walls of the alveoli. Smoking further diminishes the lungs defenses by impairing the function of the tiny hair-like cells (cilia) that line the airways and normally carry mucus toward the mouth and thus expel bacteria and toxic substances from the lung. Alpha anti-trypsin is a protein produced by the body- it s role is to inhibit the activity of the enzyme neutrophil elastase and thereby preventing damage to the alveoli. In a rare hereditary condition, there is little or no alpha anti-trypsin produced in the body and in these people emphysema develops by early middle age, especially in smokers.. Prevention: Avoidance of smoking is the most important measure. ...
When testing doesnt find a mutation, there are two possible explanations - you may not have inherited either of the mutations that cause Alpha-1 in your family or the mutation that causes Alpha-1 in your family cant be found with the test that was done. In this situation, a normal result doesnt rule out the chance that you are an Alpha-1 carrier. However, it is very unlikely that you have Alpha-1 or are a carrier. Genetic testing finds about 95% of the mutations that cause Alpha-1 ...
Raise awareness of Alpha-1 Antitrypsin Deficiency Alpha-1 Antitrypsin Deficiency is considered a rare genetic disorder with only 100,000 diagnosed cases in the U. S. We believe it is just MISSED...
This page was last edited 13:27, 12 December 2017 by Mazia. Based on work by Anthony Gallo, Irfan Dotani, Kalsang Dolma, Raviteja Reddy Guddeti, Varun Kumar, Kristin Feeney, Varun Kumar, Scott Williams, Alexandra, Cafer Zorkun, [email protected] and Jacki Buros (bot) and wikidoc anonymous user Bobblehead ...
A multidisciplinary team at the University of Pittsburgh will be leading a national effort to explore the relationships between the bacteria that live in the lungs, gene activation patterns, and disease progression.
Looking for online definition of a1-antitrypsin deficiency panniculitis in the Medical Dictionary? a1-antitrypsin deficiency panniculitis explanation free. What is a1-antitrypsin deficiency panniculitis? Meaning of a1-antitrypsin deficiency panniculitis medical term. What does a1-antitrypsin deficiency panniculitis mean?
Oxidative stress in the brain is suggested to be involved in the pathophysiology of Alzheimers disease (AD). In this study, serum alpha- and gamma-tocopherol, the two major systemic antioxidants, were analyzed at two examinations of the ULSAM-study, a longitudinal, community-based study of elderly men (age 70, n = 616 and age 77, n = 761). In addition, urinary F2-isoprostane levels, as markers of systemic oxidative stress, were analyzed at the age of 77 in this cohort (n = 679). Cox regression analyses were used to examine associations between serum alpha-, gamma-tocopherol and urinary F2-isoprostane levels and AD, any type of dementia (all-cause dementia) and non-AD dementia. On follow-up (median, 12.3 years), 40 subjects developed AD and 86 subjects developed all-cause dementia. Serum alpha- and gamma-tocopherol or urinary F2-isoprostane levels were not associated with the future risk of AD or dementia. In conclusion, systemic serum alpha- and gamma-tocopherol and urinary F2-isoprostane ...
Governor of Virginia, Governor of Virginia Terry McAuliffe, Common Ground for Virginia, McAuliffe, Terence McAuliffe, Terry McAuliffe, governor, virginia, va, commonwealth, 72nd,Governor of Virginia, Governor, Alpha-1 Antitrypsin Deficiency Awareness Month
COPD is a term that refers to a large group of lung diseases that can interfere with normal breathing. According to the American Lung Association, more than 12 million Americans have COPD, and an additional 12 million may have impaired lung function, suggesting it may be significantly underreported. As many as 24 million people may be affected. The two most common conditions of COPD are chronic bronchitis and emphysema.. The causes of COPD are not fully understood. It is generally agreed that the most important cause of chronic bronchitis and emphysema is cigarette smoking. Causes such as air pollution and occupational exposures may play a role, especially when combined with cigarette smoking. Heredity also plays a contributing role in some patients emphysema, and is especially important in a rare form due to alpha 1 anti-trypsin deficiency.. Patients with chronic bronchitis usually have a cough and sputum production for many years before they develop shortness of breath.. Patients with ...
Introduction. Cystic fibrosis (CF) is the most common and lethal autosomal recessive genetic diseases and affects one in 2,500 Caucasians. The risk of its heterozygote in the general population is one to 25. More than 1,000 mutations have been identified to the CFTR gene1, which codes for a protein containing 1,489 amino acids. Cystic Fibrosis is characterized by abnormal chlorine flow at the apical membrane of epithelial cells, causing diverse clinical manifestations including pancreatic insufficiency, lung disease, meconium ileus, elevated sweat chlorine levels and obstruction of the vas deferens. The extreme diversity of CF phenotypes is probably influenced by other genetic areas, distant from the CFTR locus. Many of the genes that are studied nowadays as modifiers of CF, particularly among those that influence the severity of the lung disease, are involved in controlling infection, immunity and inflammation. Some of these include the class II HLA antigens, mannose-binding lectin and alpha 1 ...
Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterised by excessive neutrophil degranulation and a protease: anti-protease imbalance leading to premature emphysema. Current specialised treatment for AATD consists of once weekly infusion of plasma purified AAT. Neutrophil degranulation is under the control of small GTP-binding proteins, including Ras-related C3 botulinum toxin substrate 2 (Rac2). The molecular basis for aberrant neutrophil degranulation in AATD has not been elucidated to date. The aim of this study was to fully characterise neutrophil degranulation in AATD and to determine the effects of AAT augmentation therapy on the AATD neutrophil. In this study, we examined degranulation by AATD neutrophils by Western blotting. This revealed a 3-fold increase in levels of myeloperoxidase (MPO), human cathelicidin antimicrobial protein (hCAP-18) and matrix metalloprotease-9 (MMP-9), markers of primary, secondary and tertiary granules, respectively (p=0.023, p=0.036 and p=0.042, respectively).
A 58 year old white man presented with sudden painless loss of vision to the right eye. Vision was hand movements in the right eye and 6/6 in the left. Funduscopy revealed an acute right CRAO with macular oedema. There were no signs of uveitis or retinal vasculitis. Management consisted of intravenous acetazolamide (500 mg), ocular massage, and anterior chamber paracentesis. He was subsequently sent home with aspirin treatment, and referred to his family doctor for routine risk factors assessment.. The following morning, he returned to the eye casualty department with a left CRAO, which was treated in the same way. Vision was 6/60 in the right eye and hand movements in the left. Systemic inquiry revealed a 2 month history of general malaise, arthralgia, and myalgia. General examination revealed evidence of vasculitic rash (Fig 1) affecting the right elbow and nailfold infarcts (Fig 2). He was admitted for further investigation. His erythrocyte sedimentation rate in the first hour was 128 mm and ...
Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you. The results for both activity and antigen tests are given as percentages. Different labs use slightly different normal ranges, but in general, 80% to 120% is considered normal for adults. Newborns usually have about half as much antithrombin as adults. Thrombin levels in infants rise to adult levels by about 6 months of age. People with genetically inherited antithrombin deficiency typically have test results between 40% and 60%. In both type 1 and type 2 AT deficiency, the antithrombin activity test shows a low result because you dont have as much working antithrombin as you should have. When the AT activity test shows that levels are low, the antithrombin antigen test can then be used to find out whether the deficiency is type 1 or type 2. If the follow-up ...

Alpha-1 Antitrypsin Deficiency (AATD) | Boston Childrens HospitalAlpha-1 Antitrypsin Deficiency (AATD) | Boston Children's Hospital

Learn more about Alpha-1 Antitrypsin Deficiency (AATD) symptoms, diagnosis, and treatments from experts at Boston Childrens, ... Alpha-1 Antitrypsin Deficiency (AATD) in Children. Alpha-1 antitrypsin deficiency (AATD) is the lack of a protein made by the ... The alpha-1 protein is designed to protect tissues in the body from being attacked by its own enzymes. Children with AATD ... either dont produce enough of the alpha-1 protein or the protein produced is abnormal and, therefore, is not released into the ...
more infohttp://www.childrenshospital.org/conditions-and-treatments/conditions/a/alpha-1-antitrypsin-deficiency-aatd/overview

Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease...Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease...

Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease (chronic obstructive pulmonary disease or ... Alpha-1 antitrypsin deficiency is an inherited disorder that can cause chronic obstructive pulmonary disease (COPD). People who ... To review the benefits and harms of augmentation therapy with intravenous alpha-1 antitrypsin in patients with alpha-1 ... We reviewed the benefits and harms of treating patients who have the form of the disease that affects the lungs with alpha-1 ...
more infohttp://www.cochrane.org/CD007851/AIRWAYS_intravenous-alpha-1-antitrypsin-augmentation-therapy-treating-patients-alpha-1-antitrypsin

The incidence of alpha-1-antitrypsin (A1AT) deficiency alleles in population of Central Poland - preliminary results from...The incidence of alpha-1-antitrypsin (A1AT) deficiency alleles in population of Central Poland - preliminary results from...

alpha-1 antitrypsin deficiency. S allele. Z allele. genotyping. blood concentration. DBS. prevalence. newborns. Poland. ... Inherited alpha-1 antitrypsin deficiency (A1ATD) is listed among the three most common genetic disorders in Caucasians. It ... Inherited alpha-1 antitrypsin deficiency (A1ATD) is listed among the three most common genetic disorders in Caucasians. It ... The incidence of alpha-1-antitrypsin (A1AT) deficiency alleles in population of Central Poland - preliminary results from ...
more infohttps://journals.viamedica.pl/advances_in_respiratory_medicine/article/view/27565

Serum Elastase Activity, Serum Elastase Inhibitors, and Occurrence of Carotid Atherosclerotic Plaques | CirculationSerum Elastase Activity, Serum Elastase Inhibitors, and Occurrence of Carotid Atherosclerotic Plaques | Circulation

The role of alpha 1-antitrypsin deficiency in the pathogenesis of immune disorders. Clin Immunol Immunopathol. 1985; 35: 363- ... The age- and sex-adjusted ORs for quartile 1 (lowest values), quartiles 2 to 3, and quartile 4 (highest values) of serum ... The major source of the elastase inhibitors determined in this investigation was α1-proteinase inhibitor and, to a lesser ... The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the ...
more infohttp://circ.ahajournals.org/content/105/22/2638

Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency<...Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency<...

Serum proteins associated with emphysema progression in severe alpha-1 antitrypsin deficiency. ... 7. Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. The Alpha-1-Antitrypsin Deficiency ... Abbreviations: alpha-1 antitrypsin deficiency, AATD; chronic obstructive pulmonary disease, COPD; protease inhibitor ZZ, PiZZ; ... Running Head: Serum Proteins with Emphysema in Alpha-1. Funding Support: The QUANTUM-1 Study was supported by the National ...
more infohttps://journal.copdfoundation.org/jcopdf/id/1160/Serum-Proteins-Associated-with-Emphysema-Progression-in-Severe-Alpha-1-Antitrypsin-Deficiency

Diagnosis and management of α1-antitrypsin deficiency in Europe : an expert surveyDiagnosis and management of α1-antitrypsin deficiency in Europe : an expert survey

Diagnosis and management of alpha 1-antitrypsin deficiency in Europe : an expert survey ... I. Horvath et al., "Diagnosis and management of α1-antitrypsin deficiency in Europe : an expert survey," ERJ OPEN RESEARCH, vol ... Diagnosis and management of α1-antitrypsin deficiency in Europe : an expert survey. Ildikó Horvath, Maria Canotilho, Jan ... "Diagnosis and Management of Α1-antitrypsin Deficiency in Europe : an Expert Survey." ERJ OPEN RESEARCH 5.1 (2019): n. pag. ...
more infohttps://biblio.ugent.be/publication/8610527

Protein-losing Enteropathy. PLE information. What is PLE? | PatientProtein-losing Enteropathy. PLE information. What is PLE? | Patient

Alpha-1-antitrypsin (A1AT):. *A1AT is a protein synthesised in the liver that is neither actively secreted nor absorbed. ... Investigations[1]. The initial step in the evaluation of any patient with hypoproteinaemia and/or hypoalbuminaemia is to ... PLE is a common complication of Fontans operation.[1]This is a procedure carried out in children with severe congenital heart ... PLE is a common complication of Fontans operation.[1]Heparin produces benefits independent of its anticoagulant effect.[8] ...
more infohttps://patient.info/doctor/protein-losing-enteropathy

Physio And Health: PROTEIN-LOSING ENTEROPATHYPhysio And Health: PROTEIN-LOSING ENTEROPATHY

The diagnosis is confirmed by measurement of the faecal clearence of endogenous alpha 1-antitrypsin.. Management. Treatment is ...
more infohttps://physioandhealth.blogspot.com/2011/03/protein-losing-enteropathy.html

Neutrophil Elastase (Bone Marrow Serine Protease or Elastase 2 or Medullasin or PMN Elastase or Human Leukocyte Elastase or...Neutrophil Elastase (Bone Marrow Serine Protease or Elastase 2 or Medullasin or PMN Elastase or Human Leukocyte Elastase or...

Alpha- Antitrypsin Deficiency, Bronchiolitis Obliterans, Chronic Obstructive Pulmonary Disease (COPD), Ischemia Reperfusion ... Small Molecule 1 to Inhibit Neutrophil Elastase for Immunology, Oncology and Respiratory Disorders - Drug Profile. Product ... Currently, The molecules developed by companies in Phase II, Phase I, Preclinical, Discovery and Unknown stages are 3, 2, 1, 1 ... Dormant Products, H2 2017 (Contd..1), H2 2017. Dormant Products, H2 2017 (Contd..2), H2 2017. Discontinued Products, H2 2017. ...
more infohttp://www.reportsnreports.com/reports/1173538-neutrophil-elastase-bone-marrow-serine-protease-or-elastase-2-or-medullasin-or-pmn-elastase-or-human-leukocyte-elastase-or-elane-or-ec-342137-pipeline-review-h2-2017.html

Alpha-1 antitrypsin - WikipediaAlpha-1 antitrypsin - Wikipedia

DeMeo DL, Silverman EK (March 2004). "Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: ... Recombinant alpha-1 antitrypsin is not yet available for use as a drug but is under investigation as a therapy for alpha-1 ... Alpha-1-antitrypsin or α1-antitrypsin (A1AT, A1A, or AAT) is a protein belonging to the serpin superfamily. It is encoded in ... The alpha region can be further divided into two sub-regions, termed "1" and "2". Alpha-1 antitrypsin is the main protein of ...
more infohttps://en.wikipedia.org/wiki/Alpha-1_antitrypsin

Alpha-1 Antitrypsin | Lab Tests OnlineAlpha-1 Antitrypsin | Lab Tests Online

Alpha-1 antitrypsin tests help diagnose alpha-1 antitrypsin deficiency. ... Alpha-1 antitrypsin (AAT) is a protein that protects the lungs from damage caused by activated enzymes. ... Antitrypsin_Deficiency/article.htm.. Alpha-1-Antitrypsin and Alpha-1-Antitrypsin Phenotype. ARUPs Guide to Clinical Laboratory ... Alpha-1 antitrypsin testing may be ordered when:. *An infant has jaundice that lasts for more than a week or two, an enlarged ...
more infohttps://labtestsonline.org/tests/alpha-1-antitrypsin

What Is Alpha-1 Antitrypsin Deficiency Disorder? - Scientific AmericanWhat Is Alpha-1 Antitrypsin Deficiency Disorder? - Scientific American

What is alpha-1 antitrypsin deficiency?. It is a genetic defect in the production of a protective protein called alpha-1 ... If Jackson has alpha-1 antitrypsin deficiency, it means he cannot protect his lungs from his bodys own defenses against ... What Is Alpha-1 Antitrypsin Deficiency Disorder?. An unauthorized biographer claims that pop star Michael Jackson is suffering ... What Is Alpha-1 Antitrypsin Deficiency Disorder?An unauthorized biographer claims that pop star Michael Jackson is suffering ...
more infohttps://www.scientificamerican.com/article/michael-jackson-alpha-1-antitryps/

Therapeutic Strategies for Alpha-1 Antitrypsin Deficiency - RTITherapeutic Strategies for Alpha-1 Antitrypsin Deficiency - RTI

Alpha-1 antitrypsin (AAT) deficiency is a common genetic disease, with up to 4% of the population carrying an abnormal AAT gene ... Therapeutic Strategies for Alpha-1 Antitrypsin Deficiency. What is alpha-1 antitrypsin deficiency? Alpha-1 antitrypsin (AAT) ... It affects between 1:1500 and 1:3500 in people of European descent. It is the 2nd most common genetic disorder in Ireland, ... where 1:25 people carry the mutant gene. It is rare in Asians. ...
more infohttps://www.umassmed.edu/rti/technology/alpha-1-antitrypsin-deficiency/

Alpha 1 Anti-Trypsin Deficiency - HealthLibraryAlpha 1 Anti-Trypsin Deficiency - HealthLibrary

Alpha 1 anti-trypsin (AAT) deficiency is a rare genetic problem. It causes low levels of the enzyme AAT or stops it from ... Alpha-1 antitrypsin deficiency. National Jewish Health website. Available at: ...(Click grey area to select URL). Accessed ... Alpha-1 antitrypsin deficiency. The Merck Manual Professional Edition website. Available at: ...(Click grey area to select URL) ... Alpha 1 Anti-Trypsin Deficiency. (AAT Deficiency; Alpha-1 Antiprotease Deficiency). Pronounced: Al-fa-wun An-tee-TRIP-sin Dee- ...
more infohttp://healthlibrary.epnet.com/GetContent.aspx?token=ffe89542-7047-469b-aadd-ceea6d53cb65&chunkiid=608357

Alpha 1 Antitrypsin Deficiency Clinical Research Trials | CenterWatchAlpha 1 Antitrypsin Deficiency Clinical Research Trials | CenterWatch

Alpha 1 Antitrypsin Deficiency Clinical Research Trial Listings in Gastroenterology Pulmonary/Respiratory Diseases Hepatology ( ... Alpha 1 Antitrypsin Deficiency Clinical Trials. A listing of Alpha 1 Antitrypsin Deficiency medical research trials actively ... Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human) Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema ... double blind clinical study to assess the efficacy and safety of two separate dose regimens of Alpha-1 MP versus placebo for ...
more infohttps://www.centerwatch.com/clinical-trials/listings/condition/258/alpha-1-antitrypsin-deficiency/?&phase=3

Alpha 1 Antitrypsin Deficiency Clinical Research Trials | CenterWatchAlpha 1 Antitrypsin Deficiency Clinical Research Trials | CenterWatch

Alpha 1 Antitrypsin Deficiency Clinical Research Trial Listings in Gastroenterology Pulmonary/Respiratory Diseases Hepatology ( ... Alpha-1 Antitrypsin Deficiency occurs when there is a lack of a protein in the blood called alpha-1 antitrypsin, or AAT. AAT is ... Alpha-1 Foundation Research Registry The Registry was established in 1997 by the Alpha-1 Foundation to facilitate research ... Alpha-1 Coded Testing(ACT) Study Genetic testing for alpha-1 antitrypsin deficiency is sometimes delayed despite established ...
more infohttps://www.centerwatch.com/clinical-trials/listings/condition/258/alpha-1-antitrypsin-deficiency/?page=1

Alpha-1 antitrypsin deficiency - SNPediaAlpha-1 antitrypsin deficiency - SNPedia

Depending on the genetic variant, alpha-1 antitrypsin deficiency can lead to chronic obstructive pulmonary disease (COPD) or ... SNPs associated with reduced levels of the enzyme alpha-1 antitrypsin (encoded by the SERPINA1 gene): ... Retrieved from "https://www.SNPedia.com/index.php?title=Alpha-1_antitrypsin_deficiency&oldid=1298471" ...
more infohttps://www.snpedia.com/index.php/Alpha-1_antitrypsin_deficiency

Alpha-1 Antitrypsin Deficiency - Penn MedicineAlpha-1 Antitrypsin Deficiency - Penn Medicine

Alpha-1 antitrypsin (A1AT) deficiency is a condition in which the body does not make enough of a protein that protects the ... a1-Antitrypsin deficiency and emphysema. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics ... a1-antitrypsin deficiency. Clin Chest Med. 2016;37(3):487-504. PMID: 27514595 www.ncbi.nlm.nih.gov/pubmed/27514595. ... AAT deficiency; Alpha-1 protease deficiency; COPD - alpha-1 antitrypsin deficiency; Cirrhosis - alpha-1 antitrypsin deficiency ...
more infohttps://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/alpha-1-antitrypsin-deficiency

Alpha-1 Antitrypsin DeficiencyAlpha-1 Antitrypsin Deficiency

This program explains what alpha-1 antitrypsin deficiency is and what causes it. It also covers how AAT deficiency is diagnosed ... Alpha-1 Antitrypsin Deficiency. This program explains what alpha-1 antitrypsin deficiency is and what causes it. It also covers ...
more infohttp://www.patient-education.com/english/topic/alpha-1-antitrypsin-deficiency

Alpha 1-antitrypsin deficiency overview --Doctors LoungeAlpha 1-antitrypsin deficiency overview --Doctors Lounge

Normally, alpha 1-antitrypsin is produced in the liver and exists in levels of 1.5-3.5 gram/litre. When the levels are reduced ... Alpha 1-antitrypsin deficiency (A1AD) is a genetic disorder caused by reduced levels of alpha 1-antitrypsin in blood. It leads ... Apart from increasing the inflammatory reaction in the airways, cigarette smoke also directly inactivates alpha 1-antitrypsin ... Please refer to the alpha 1-antitrypsin for the various protease inhibitor (Pi) genotypes and phenotypes. ...
more infohttps://www.doctorslounge.com/index.php/reference/diseases/121

Anti-alpha 1 Antitrypsin antibody, prediluted (ab74664)Anti-alpha 1 Antitrypsin antibody, prediluted (ab74664)

Rabbit polyclonal alpha 1 Antitrypsin antibody validated for IHC and tested in Human, Hrs, Mink, Mk and Bb. Immunogen ... Anti-alpha 1 Antitrypsin antibody, prediluted. See all alpha 1 Antitrypsin primary antibodies. ... Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - alpha 1 Antitrypsin antibody, prediluted (ab74664) ...
more infohttp://www.abcam.com/alpha-1-antitrypsin-antibody-prediluted-ab74664.html

Alpha-1-antitrypsin subtypes in Polish newborns.Alpha-1-antitrypsin subtypes in Polish newborns.

Alpha-1-antitrypsin phenotypes of umbilical cord serum from 741 Polish newborns were studied by isoelectric focusing. The ... Alpha-1-antitrypsin phenotypes of umbilical cord serum from 741 Polish newborns were studied by isoelectric focusing. The ...
more infohttp://www.biomedsearch.com/nih/Alpha-1-antitrypsin-subtypes-in/8537083.html

alpha-1-antitrypsin ELISA Kits | Biocompare.comalpha-1-antitrypsin ELISA Kits | Biocompare.com

Compare alpha-1-antitrypsin ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, ... Bovine Alpha-1-antitrypsin, SERPINA1 ELISA Kit *Detection Target: serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, ... SERPINA2 (Putative alpha-1-antitrypsin-related protein) BioAssay™ ELISA Kit (Human) *Detection Target: SERPINA2 (Putative alpha ... Your search returned 339 alpha-1-antitrypsin ELISA ELISA Kit across 25 suppliers. ...
more infohttp://www.biocompare.com/pfu/110627/soids/2-36440/Assay_Kit/ELISA_alpha-1-antitrypsin

Alpha-1 Antitrypsin Deficiency | National Heart, Lung, and Blood Institute (NHLBI)Alpha-1 Antitrypsin Deficiency | National Heart, Lung, and Blood Institute (NHLBI)

Alpha-1 antitrypsin (AAT) deficiency is an inherited condition in which you do not have enough of a protein, AAT, causing a ... What Is - Alpha-1 Antitrypsin Deficiency. Alpha-1 antitrypsin (an-tee-TRIP-sin) deficiency, or AAT deficiency, is a condition ... Diagnosis - Alpha-1 Antitrypsin Deficiency. Alpha-1 antitrypsin (AAT) deficiency usually is diagnosed after you develop a lung ... Risk Factors - Alpha-1 Antitrypsin Deficiency. Alpha-1 antitrypsin (AAT) deficiency occurs in all ethnic groups. However, the ...
more infohttps://www.nhlbi.nih.gov/health-topics/alpha-1-antitrypsin-deficiency
  • 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 (AAT) is a protein in the blood that protects the lungs from damage caused by activated enzymes . (labtestsonline.org)
  • 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)
  • Alpha-1 antitrypsin (AAT) is a protein normally found in the lungs and the bloodstream. (northshore.org)
  • Available at: http://www.merckmanuals.com/professional/pulmonary%5Fdisorders/chronic%5Fobstructive%5Fpulmonary%5Fdisease%5Fand%5Frelated%5Fdisorders/alpha-1%5Fantitrypsin%5Fdeficiency.html. (winchesterhospital.org)
  • As ?1-antitrypsin is an acute phase reactant, its transcription is markedly increased during inflammation elsewhere in response to increased interleukin-1 and 6 and TNF? (doctorslounge.com)
  • 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)
  • The Registry was established in 1997 by the Alpha-1 Foundation to facilitate research initiatives and promote the development of improved treatments and a cure for Alpha-1. (centerwatch.com)