A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
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.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
The mucous lining of the NASAL CAVITY, including lining of the nostril (vestibule) and the OLFACTORY MUCOSA. Nasal mucosa consists of ciliated cells, GOBLET CELLS, brush cells, small granule cells, basal cells (STEM CELLS) and glands containing both mucous and serous cells.
Inorganic compounds that contain gold as an integral part of the molecule.
Inorganic binary compounds of iodine or the I- ion.
Established cell cultures that have the potential to propagate indefinitely.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
The mucous membrane lining the RESPIRATORY TRACT, including the NASAL CAVITY; the LARYNX; the TRACHEA; and the BRONCHI tree. The respiratory mucosa consists of various types of epithelial cells ranging from ciliated columnar to simple squamous, mucous GOBLET CELLS, and glands containing both mucous and serous cells.
Benzoic acids, salts, or esters that contain an amino group attached to carbon number 2 or 6 of the benzene ring structure.
Phenols substituted in any position by an amino group.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
An inhibitor of anion conductance including band 3-mediated anion transport.
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.
A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching.
The fluid excreted by the SWEAT GLANDS. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
A red fluorescein dye used as a histologic stain. It may be cytotoxic, mutagenic, and inhibit certain mitochondrial functions.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Benzoic acid or benzoic acid esters substituted with one or more nitro groups.
The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI.
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.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation.
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.
The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
Organic salts or esters of methanesulfonic acid.
Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.
Incorporation of biotinyl groups into molecules.
A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.
Reduced (protonated) form of THIAZOLES. They can be oxidized to THIAZOLIDINEDIONES.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
A plasma membrane exchange glycoprotein transporter that functions in intracellular pH regulation, cell volume regulation, and cellular response to many different hormones and mitogens.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
The ability of a substrate to allow the passage of ELECTRONS.
Proteins prepared by recombinant DNA technology.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct.
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)
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Deletion of sequences of nucleic acids from the genetic material of an individual.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Electroneutral chloride bicarbonate exchangers that allow the exchange of BICARBONATE IONS exchange for CHLORIDE IONS across the cellular membrane. The action of specific antiporters in this class serve important functions such as allowing the efficient exchange of bicarbonate across red blood cell membranes as they passage through capillaries and the reabsorption of bicarbonate ions by the kidney.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The rate dynamics in chemical or physical systems.
Ducts that collect PANCREATIC JUICE from the PANCREAS and supply it to the DUODENUM.
Sweat-producing structures that are embedded in the DERMIS. Each gland consists of a single tube, a coiled body, and a superficial duct.
A constitutively expressed subfamily of the HSP70 heat-shock proteins. They preferentially bind and release hydrophobic peptides by an ATP-dependent process and are involved in post-translational PROTEIN TRANSLOCATION.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
Infections with bacteria of the genus PSEUDOMONAS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Organic salts of cyanic acid containing the -OCN radical.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Membrane transporters that co-transport two or more dissimilar molecules in the opposite direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A non-specific host defense mechanism that removes MUCUS and other material from the LUNGS by ciliary and secretory activity of the tracheobronchial submucosal glands. It is measured in vivo as mucus transfer, ciliary beat frequency, and clearance of radioactive tracers.
Glands of external secretion that release its secretions to the body's cavities, organs, or surface, through a duct.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
A subclass of symporters that specifically transport SODIUM CHLORIDE and/or POTASSIUM CHLORIDE across cellular membranes in a tightly coupled process.
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.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.
A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.
Inorganic salts of phosphoric acid that contain two phosphate groups.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Family of small, surface-dwelling fish that inhabit fresh and brackish waters, and coastal marine areas.
Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)
The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells.
Na-K-Cl transporter ubiquitously expressed. It plays a key role in salt secretion in epithelial cells and cell volume regulation in nonepithelial cells.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.
Organic derivatives of thiocyanic acid which contain the general formula R-SCN.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
An individual in which both alleles at a given locus are identical.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The process of cleaving a chemical compound by the addition of a molecule of water.
An individual having different alleles at one or more loci regarding a specific character.
A lectin found in ENDOPLASMIC RETICULUM membranes that binds to specific N-linked OLIGOSACCHARIDES found on newly synthesized proteins. It may play role in PROTEIN FOLDING or retention and degradation of misfolded proteins in the endoplasmic reticulum.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Drugs used for their effects on the respiratory system.
Elements of limited time intervals, contributing to particular results or situations.
Proteins produced from GENES that have acquired MUTATIONS.
The inactive proenzyme of trypsin secreted by the pancreas, activated in the duodenum via cleavage by enteropeptidase. (Stedman, 25th ed)
Congenital structural abnormalities of the UROGENITAL SYSTEM in either the male or the female.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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).
Peptides that regulate the WATER-ELECTROLYTE BALANCE in the body, also known as natriuretic peptide hormones. Several have been sequenced (ATRIAL NATRIURETIC FACTOR; BRAIN NATRIURETIC PEPTIDE; C-TYPE NATRIURETIC PEPTIDE).
Organic or inorganic compounds that contain the -N3 group.
Focal accumulations of EDEMA fluid in the NASAL MUCOSA accompanied by HYPERPLASIA of the associated submucosal connective tissue. Polyps may be NEOPLASMS, foci of INFLAMMATION, degenerative lesions, or malformations.
Paired respiratory organs of fishes and some amphibians that are analogous to lungs. They are richly supplied with blood vessels by which oxygen and carbon dioxide are exchanged directly with the environment.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A sulfamyl diuretic.
Biochemical identification of mutational changes in a nucleotide sequence.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Proteins that cotransport sodium ions and bicarbonate ions across cellular membranes.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Green dyes containing ammonium and aryl sulfonate moieties that facilitate the visualization of tissues, if given intravenously. They have mostly been used in the study of kidney physiology.
High molecular weight insoluble polymers which contain functional anionic groups that are capable of undergoing exchange reactions with cations.
The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.
Liquid components of living organisms.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Transport proteins that carry specific substances in the blood or across cell membranes.
A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.
A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
Miscellaneous agents found useful in the symptomatic treatment of diarrhea. They have no effect on the agent(s) that cause diarrhea, but merely alleviate the condition.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.
Uricosuric that acts by increasing uric acid clearance. It is used in the treatment of gout.
Membrane proteins whose primary function is to facilitate the transport of negatively charged molecules (anions) across a biological membrane.
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Devices used in a technique by which cells or tissues are grown in vitro or, by implantation, in vivo within chambers permeable to diffusion of solutes across the chamber walls. The chambers are used for studies of drug effects, osmotic responses, cytogenic and immunologic phenomena, metabolism, etc., and include tissue cages.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
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.
Phenols substituted with one or more chlorine atoms in any position.
The balance of fluid in the BODY FLUID COMPARTMENTS; total BODY WATER; BLOOD VOLUME; EXTRACELLULAR SPACE; INTRACELLULAR SPACE, maintained by processes in the body that regulate the intake and excretion of WATER and ELECTROLYTES, particularly SODIUM and POTASSIUM.
A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.
A genus of owlet moths of the family Noctuidae. These insects are used in molecular biology studies during all stages of their life cycle.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.
An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3.

Cystic fibrosis transmembrane conductance regulator-mediated corneal epithelial cell ingestion of Pseudomonas aeruginosa is a key component in the pathogenesis of experimental murine keratitis. (1/2621)

Previous findings indicate that the cystic fibrosis transmembrane conductance regulator (CFTR) is a ligand for Pseudomonas aeruginosa ingestion into respiratory epithelial cells. In experimental murine keratitis, P. aeruginosa enters corneal epithelial cells. We determined the importance of CFTR-mediated uptake of P. aeruginosa by corneal cells in experimental eye infections. Entry of noncytotoxic (exoU) P. aeruginosa into human and rabbit corneal cell cultures was inhibited with monoclonal antibodies and peptides specific to CFTR amino acids 108 to 117. Immunofluorescence microscopy and flow cytometry demonstrated CFTR in the intact murine corneal epithelium, and electron microscopy showed that CFTR binds to P. aeruginosa following corneal cell ingestion. In experimental murine eye infections, multiple additions of 5 nM CFTR peptide 103-117 to inocula of either cytotoxic (exoU+) or noncytotoxic P. aeruginosa resulted in large reductions in bacteria in the eye and markedly lessened eye pathology. Compared with wild-type C57BL/6 mice, heterozygous DeltaF508 Cftr mice infected with P. aeruginosa had an approximately 10-fold reduction in bacterial levels in the eye and consequent reductions in eye pathology. Homozygous DeltaF508 Cftr mice were nearly completely resistant to P. aeruginosa corneal infection. CFTR-mediated internalization of P. aeruginosa by buried corneal epithelial cells is critical to the pathogenesis of experimental eye infection, while in the lung, P. aeruginosa uptake by surface epithelial cells enhances P. aeruginosa clearance from this tissue.  (+info)

Cystic fibrosis-associated mutations at arginine 347 alter the pore architecture of CFTR. Evidence for disruption of a salt bridge. (2/2621)

Arginine 347 in the sixth transmembrane domain of cystic fibrosis transmembrane conductance regulator (CFTR) is a site of four cystic fibrosis-associated mutations. To better understand the function of Arg-347 and to learn how mutations at this site disrupt channel activity, we mutated Arg-347 to Asp, Cys, Glu, His, Leu, or Lys and examined single-channel function. Every Arg-347 mutation examined, except R347K, had a destabilizing effect on the pore, causing the channel to flutter between two conductance states. Chloride flow through the larger conductance state was similar to that of wild-type CFTR, suggesting that the residue at position 347 does not interact directly with permeating anions. We hypothesized that Arg-347 stabilizes the channel through an electrostatic interaction with an anionic residue in another transmembrane domain. To test this, we mutated anionic residues (Asp-924, Asp-993, and Glu-1104) to Arg in the context of either R347E or R347D mutations. Interestingly, the D924R mutation complemented R347D, yielding a channel that behaved like wild-type CFTR. These data suggest that Arg-347 plays an important structural role in CFTR, at least in part by forming a salt bridge with Asp-924; cystic fibrosis-associated mutations disrupt this interaction.  (+info)

CFTR channel insertion to the apical surface in rat duodenal villus epithelial cells is upregulated by VIP in vivo. (3/2621)

cAMP activated insertion of the cystic fibrosis transmembrane conductance regulator (CFTR) channels from endosomes to the apical plasma membrane has been hypothesized to regulate surface expression and CFTR function although the physiologic relevance of this remains unclear. We previously identified a subpopulation of small intestinal villus epithelial cells or CFTR high expressor (CHE) cells possessing very high levels of apical membrane CFTR in association with a prominent subapical vesicular pool of CFTR. We have examined the subcellular redistribution of CFTR in duodenal CHE cells in vivo in response to the cAMP activated secretagogue vasoactive intestinal peptide (VIP). Using anti-CFTR antibodies against the C terminus of rodent CFTR and indirect immunofluorescence, we show by quantitative confocal microscopy that CFTR rapidly redistributes from the cytoplasm to the apical surface upon cAMP stimulation by VIP and returns to the cytoplasm upon removal of VIP stimulation of intracellular cAMP levels. Using ultrastructural and confocal immunofluorescence examination in the presence or absence of cycloheximide, we also show that redistribution was not dependent on new protein synthesis, changes in endocytosis, or rearrangement of the apical cytoskeleton. These observations suggest that physiologic cAMP activated apical membrane insertion and recycling of CFTR channels in normal CFTR expressing epithelia contributes to the in vivo regulation of CFTR mediated anion transport.  (+info)

beta3-adrenoceptor control the cystic fibrosis transmembrane conductance regulator through a cAMP/protein kinase A-independent pathway. (4/2621)

In human cardiac myocytes, we have previously identified a functional beta3-adrenoceptor in which stimulation reduces action potential duration. Surprisingly, in cardiac biopsies obtained from cystic fibrosis patients, beta3-adrenoceptor agonists produced no effects on action potential duration. This result suggests the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) chloride current in the electrophysiological effects of beta3-adrenoceptor stimulation in non-cystic fibrosis tissues. We therefore investigated the control of CFTR activity by human beta3-adrenoceptors in a recombinant system: A549 human cells were intranuclearly injected with plasmids encoding CFTR and beta3-adrenoceptors. CFTR activity was functionally assayed using the 6-methoxy-N-(3-sulfopropyl)quinolinium fluorescent probe and the patch-clamp technique. Injection of CFTR-cDNA alone led to the expression of a functional CFTR protein activated by cAMP or cGMP. Co-expression of CFTR (but not of mutated DeltaF508-CFTR) with high levels of beta3-adrenoceptor produced an increased halide permeability under base-line conditions that was not further sensitive to cAMP or beta3-adrenoceptor stimulation. Patch-clamp experiments confirmed that CFTR channels were permanently activated in cells co-expressing CFTR and a high level of beta3-adrenoceptor. Permanent CFTR activation was not associated with elevated intracellular cAMP or cGMP levels. When the expression level of beta3-adrenoceptor was lowered, CFTR was not activated under base-line conditions but became sensitive to beta3-adrenoceptor stimulation (isoproterenol plus nadolol, SR 58611, or CGP 12177). This later effect was not prevented by protein kinase A inhibitors. Our results provide molecular evidence that CFTR but not mutated DeltaF508-CFTR is regulated by beta3-adrenoceptors expression through a protein kinase A-independent pathway.  (+info)

Molecular analysis of the cystic fibrosis gene reveals a high frequency of the intron 8 splice variant 5T in Egyptian males with congenital bilateral absence of the vas deferens. (5/2621)

It has previously been shown that defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are largely responsible for the condition of congenital bilateral absence of the vas deferens (CBAVD), without associated renal abnormalities, in Caucasian populations. To assess the involvement of the CFTR in CBAVD in a population with presumed low cystic fibrosis (CF) frequency, we have analysed 20 CBAVD males from Egypt for the presence of 12 common Caucasian CFTR mutations and the intron 8 5T splice variant, IVS-5T, known to be a major cause of CBAVD in Caucasian patients. In 16 of the males without associated renal abnormalities only one deltaF508 carrier was identified, but an exceptionally high frequency of the IVS-5T variant was found (14 of 32 alleles or 43.7%), confirming that this variant is involved in many cases of CBAVD, even in populations where CF is rare. CFTR mutations or the IVS-5T variant were found neither in the remaining four patients with associated renal abnormalities nor in the spouses of the 20 CBAVD patients. However, one patient was homozygous for a leucine to proline substitution at amino acid position 541 (L541P) of the CFTR. It is as yet not clear whether this change is involved in CBAVD in this male.  (+info)

Functional dissection of the R domain of cystic fibrosis transmembrane conductance regulator. (6/2621)

Exogenously expressed unphosphorylated sub-domains of the R domain block CFTR Cl- channels in the planar lipid bilayer, though the block differs from block with full length R domain. Full length R domain peptide (aa 588-855) blocks CFTR Cl- channels quickly, completely and permanently. Two sub-domains, RD1RD2 (aa 588-805) and RD2TM (aa 672-855), also inhibit CFTR Cl- channels, but the block takes longer to effect and is not complete. Shorter sequences, RD1 (aa 588-746) and RD2 (aa 672-805), fail to effect any block. These data suggest that either the amino-terminal or carboxy-terminal portions of the R domain protein or its stabilized secondary structure are critical to functional regulation.  (+info)

Chemokine expression in CF epithelia: implications for the role of CFTR in RANTES expression. (7/2621)

To delineate the mechanisms that facilitate leukocyte migration into the cystic fibrosis (CF) lung, expression of chemokines, including interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and RANTES, was compared between CF and non-CF airway epithelia. The findings presented herein demonstrate that, under either basal conditions or tumor necrosis factor-alpha (TNF-alpha)- and/or interferon-gamma (IFN-gamma)-stimulated conditions, a consistent pattern of differences in the secretion of IL-8 and MCP-1 between CF and non-CF epithelial cells was not observed. In contrast, CF epithelial cells expressed no detectable RANTES protein or mRNA under basal conditions or when stimulated with TNF-alpha and/or IFN-gamma (P +info)

A single conductance pore for chloride ions formed by two cystic fibrosis transmembrane conductance regulator molecules. (8/2621)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent protein kinase (PKA)- and ATP-regulated chloride channel, whose gating process involves intra- or intermolecular interactions among the cytosolic domains of the CFTR protein. Tandem linkage of two CFTR molecules produces a functional chloride channel with properties that are similar to those of the native CFTR channel, including trafficking to the plasma membrane, ATP- and PKA-dependent gating, and a unitary conductance of 8 picosiemens (pS). A heterodimer, consisting of a wild type and a mutant CFTR, also forms an 8-pS chloride channel with mixed gating properties of the wild type and mutant CFTR channels. The data suggest that two CFTR molecules interact together to form a single conductance pore for chloride ions.  (+info)

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Provided herein are bioactive agents comprising a compound that inhibits the ion transport activity of a cystic fibrosis transmembrane conductance regulator (CFTR) and that is linked to a macromolecule that interacts with a cell that expresses CFTR. The bioactive agents described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, secretory diarrhea.
TY - JOUR. T1 - Intracellular cysteines of the cystic fibrosis transmembrane conductance regulator (CFTR) modulate channel gating. AU - Ketchum, Christian. AU - Yue, Hongwen. AU - Alessi, Karen. AU - Devidas, Shreenivas. AU - Guggino, William. AU - Maloney, Peter. PY - 2002/1/1. Y1 - 2002/1/1. N2 - The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette superfamily, is a cAMP-activated chloride channel. CFTR contains two transmembrane domains (TMDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain. We found that whole-cell CFTR-dependent Cl - currents in Xenopus laevis oocytes were sensitive to HgCl 2 , suggesting that modification of endogenous cysteines alters channel activity. To understand better this phenomenon, site-directed mutagenesis was employed to generate both individual cysteine replacements and a version of the molecule with no cysteines in the hydrophobic sector. Each mutant displayed a forskolin/IBMX-activated ...
Read Interactions between Impermeant Blocking Ions in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore: Evidence for Anion-Induced Conformational Changes, The Journal of Membrane Biology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
We wish to construct a mouse model for the human inherited disease cystic fibrosis. We describe here the successful targeting in embryonal stem cells of the murine homologue (Cftr) of the cystic fibrosis transmembrane conductance regulator gene, as the first critical step towards this end. The targeting event precisely disrupts exon 10, the site of the major mutation in patients with cystic fibrosis. The targeted cells are pluripotent and competent to form chimaeras.
TY - JOUR. T1 - Cystic fibrosis transmembrane conductance regulator. T2 - The NBF1 + R (nucleotide-binding fold 1 and regulatory domain) segment acting alone catalyses a Co2+/Mn2+/Mg2+-ATPase activity markedly inhibited by both Cd2+ and the transition-state analogue orthovanadate. AU - Annereau, Jean Philippe. AU - Ko, Young Hee. AU - Pedersen, Peter L.. PY - 2003/4/15. Y1 - 2003/4/15. N2 - Cystic fibrosis (CF) is caused by mutations in the gene encoding CFTR (cystic fibrosis transmembrane conductance regulator), a regulated anion channel and member of the ATP-binding-cassette transporter (ABC transporter) superfamily. Of CFTRs five domains, the first nucleotide-binding fold (NBF1) has been of greatest interest both because it is the major hotspot for mutations that cause CF, and because it is connected to a unique regulatory domain (R). However, attempts have failed to obtain a catalytically active NBF1 + R protein in the absence of a fusion partner. Here, we report that such a protein can ...
TY - JOUR. T1 - The cystic fibrosis transmembrane conductance regulator as a marker of human pancreatic duct development. AU - Hyde, K.. AU - Reid, C. J.. AU - Tebbutt, S. J.. AU - Weide, L.. AU - Hollingsworth, M. A.. AU - Harris, A.. PY - 1997. Y1 - 1997. N2 - Background and Aims: The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a small conductance adenosine 3,5-cyclic monophosphate (cAMP)activated chloride ion channel found in the apical membranes of epithelia within the pancreas, airway, intestine, bile duct, sweat gland, and male genital ducts. Pancreatic insufficiency is a feature of about 85% of patients with cystic fibrosis and is believed to be caused by pancreatic autolysis after pancreatic duct obstruction. The aim of this study was to investigate the expression of CFTR in the pancreas from early development to postnatal life to establish whether the CFTR plays a key role in development of the pancreatic duct epithelium. Methods: Expression of CFTR from the ...
We developed molecular models for the cystic fibrosis transmembrane conductance regulator chloride channel based on the prokaryotic ABC transporter, Sav1866. Here we analyze predicted pore geometry and side-chain orientations for TM3, TM6, TM9, and TM12, with particular attention being paid to the location of the rate-limiting barrier for anion conduction. Side-chain orientations assayed by cysteine scanning were found to be from 77 to 90% in accord with model predictions. The predicted geometry of the anion conduction path was defined by a space-filling model of the pore and confirmed by visualizing the distribution of water molecules from a molecular dynamics simulation. The pore shape is that of an asymmetric hourglass, comprising a shallow outward-facing vestibule that tapers rapidly toward a narrow bottleneck linking the outer vestibule to a large inner cavity extending toward the cytoplasmic extent of the lipid bilayer. The junction between the outer vestibule and the bottleneck features an
Cystic fibrosis transmembrane conductance regulator (CFTR) has been considered to be involved in the regulatory pathway of biliary mucin secretion. We investigated expression of CFTR protein and mRNA in 24 livers with hepatolithiasis, in 6 with cholangiocarcinoma, and in 12 histologically normal livers. According to the histologic features of chronic proliferative cholangitis, hepatolithiasis was subdivided into inflammatory cell infiltration predominant (N = 14) and fibrosis predominant (N = 10). The mean signal density of CFTR in overall hepatolithiasis and in histologically normal livers was 1.23 ± 0.15 and 1.01 ± 0.13, respectively (P | 0.05). The CFTR protein (1.60 ± 0.18) and mRNA (1.09 ± 0.15) in inflammatory cell infiltration predominant patients were significantly higher (CFTR protein, 1.01 ± 0.13; mRNA, 0.75 ± 0.11) than in control subjects (P | 0.05), whereas those in fibrosis-predominant patients (CFTR protein, 0.72 ± 0.15; mRNA, 0.55 ± 0.13) were less than in control subjects (P | 0
Cystic Fibrosis (CF) represents the most common life-threatening recessive genetic trait among the caucasian population, especially those of northern European descent. The disease is caused by the functional absence of a plasma membrane chloride channel, designated as the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). We are interested in investigating which proteins associate with CFTR during its biosynthesis in a manner that may determine whether or not the CFTR protein would mature into a functional plasma membrane channel. Co-immunoprecipitation procedures have been previously applied in detecting such protein-protein interactions. In these experiments, antibodies to known chaperone proteins were assessed for their ability to co-immunoprecipitate newly synthesized CFTR. While such trials successfully identified interactions co-immunoprecipitate newly synthesized CFTR. While such trials successfully identified interactions with Hsp70, calnexin and Hsp90, they do not assess the ...
Bone loss is an important clinical issue in patients with cystic fibrosis (CF). Whether the cystic fibrosis transmembrane conductance regulator (CFTR) plays a direct role in bone cell function is yet unknown. In this study, we provide evidence that inhibition of CFTR-Cl(-) channel function results in a significant decrease of osteoprotegerin (OPG) secretion accompanied with a concomitant increase of prostaglandin (PG) E(2) secretion of primary human osteoblast cultures (n=5). Our data therefore suggest that in bone cells of CF patients, the loss of CFTR activity may result in an increased inflammation-driven bone resorption (through both the reduced OPG and increased PGE(2) production), and thus might contribute to the early bone loss reported in young children with CF.
The olfactory epithelium (OE) of mice deficient in cystic fibrosis transmembrane conductance regulator (CFTR) exhibits ion transport deficiencies reported in human CF airways, as well as progressive neuronal loss, suggesting defects in olfactory neuron homeostasis. Microvillar cells, a specialized OE cell-subtype, have been implicated in maintaining tissue homeostasis. These cells are endowed with a PLCβ2/IP3 R3/TRPC6 signal transduction pathway modulating release of neuropeptide Y (NPY), which stimulates OE stem cell activity. It is unknown, however, whether microvillar cells also mediate the deficits observed in CFTR-null mice. Here we show that Cftr mRNA in mouse OE is exclusively localized in microvillar cells and CFTR immunofluorescence is coassociated with the scaffolding protein NHERF-1 and PLCβ2 in microvilli. In CFTR-null mice, PLCβ2 was undetectable, NHERF-1 mislocalized, and IP3 R3 more intensely stained, along with increased levels of NPY, suggesting profound alteration of the ...
Deletion of phenylalanine 508 (delta Phe-508) in the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes approximately 70% of all cases of cystic fibrosis. This residue lies in a region of the protein that we have synthesized chemically and shown to bind adenine nucleotides (Th …
Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis Academic Article ...
Structural information is required to define the molecular basis for chloride conduction through CFTR (cystic fibrosis transmembrane conductance regulator). Towards this goal, we expressed MSD2, the second of the two MSDs (membrane-spanning domains) of CFTR, encompassing residues 857-1158 in Sf9 cells using the baculovirus system. In Sf9 plasma membranes, MSD2 migrates as expected for a dimer in non-dissociative PAGE, and confers the appearance of an anion permeation pathway suggesting that dimeric MSD2 mediates anion flux. To assess directly the function and quaternary structure of MSD2, we purified it from Sf9 cells by virtue of its polyhistidine tag and nickel affinity. Reconstitution of MSD2 into liposomes conferred a 4,4′-di-isothiocyanostilbene-2,2′-disulphonate-inhibitable, chloride-selective electrodiffusion pathway. Further, this activity is probably mediated directly by MSD2 as reaction of its single cysteine residue (Cys866) with the thiol modifying reagent, ...
The level of the mature native 170 kDa form of CFTR (cystic fibrosis transmembrane conductance regulator) at the plasma membrane is under the control of a selective proteolysis catalysed by calpain. The product of this limited digestion, consisting of discrete fragments still associated by strong interactions, is removed from the plasma membrane and internalized in vesicles and subject to an additional degradation. This process can be monitored by visualizing the accumulation of a 100 kDa fragment in a proliferating human leukaemic T-cell line and in human circulating lymphocytes. In reconstructed systems, and in intact cells, the conversion of native CFTR into the 100 kDa fragment linearly correlated with calpain activation and was prevented by addition of synthetic calpain inhibitors. A reduction in Ca2+ influx, by blocking the NMDA (N-methyl-D-aspartate) receptor Ca2+ channel, inhibited the conversion of the native 170 kDa fragment into the 100 kDa fragment, whereas an endosome acidification ...
cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle during Low pH or Contractions. . 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.
Function and Expression of Cystic Fibrosis Transmembrane Conductance Regulator after Small Intestinal Transplantation in Mice. . 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.
Cystic fibrosis (CF) is the most common autosomal, recessive, life-span shortening disease in Caucasians. Since discovery of the gene for CF (cystic fibrosis transmembrane conductance regulator [CFTR]) in 1989, knowledge of the molecular function of this gene and its interactions has offered new the …
Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help of newer therapies, the microbiome in the lung becomes less diverse along with increased occurrences for noninfectious causes of airway diseases ...
Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasian populations. CF affects multiple organ systems including pancreas, liver, intestines, sweat glands, and male reproductive organs, however the leading cause of morbidity and mortality in CF patients is chronic lung disease. CF is caused by a mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene which leads to chloride (Cl-) and bicarbonate (HCO3-) anion dysregulation at the airway surface. Without adequate anion exchange, thick, viscous mucus accumulates at the airway surface allowing bacterial colonization to occur. Complementing CFTR in the appropriate airway cells restores the anion channel activity in CFTR-deficient cells. The ultimate goal for CF gene therapy is to design an integrating vector that would lead to persistent and efficient expression of CFTR in the airways. Performing gene therapy experiments is dependent upon a relevant animal model. The CF pig is a large animal model similar in
A cAMP-inducible chloride permeability has been detected in mouse fibroblast (L cell) lines upon stable integration of a full-length cDNA encoding the human cystic fibrosis transmembrane conductance regulator (CFTR). As indicated by a Cl--indicator dye, the Cl- permeability of the plasma membrane increases by 10- to 30-fold within 2 min after treatment of the cells with forskolin, an activator of adenylyl cyclase. The properties of the conductance are similar to those described in secretory epithelial cells; the whole-cell current-voltage relationship is linear and there is no evidence of voltage-dependent inactivation or activation. In contrast, this cAMP-dependent Cl- flux is undetectable in the untransfected cells or cells harboring defective cDNA constructs, including one with a phenylalanine deletion at amino acid position 508 (ΔF508), the most common mutation causing cystic fibrosis. These observations are consistent with the hypothesis that the CFTR is a cAMP-dependent Cl- channel. The ...
Cystic fibrosis (CF) is a genetic defect in the cystic fibrosis transmembrane conductance regulator protein and is the most common life-limiting genetic condition affecting the Caucasian population. It is an autosomal recessive, monogenic inherited disorder characterized by failure of airway host defense against bacterial infection, which results in bronchiectasis, the breakdown of airway wall extracellular matrix (ECM). In this study, we show that the in vitro models consisting of human tracheo-bronchial-epithelial (hBE) cells grown on porous supports with embedded magnetic nanoparticles (MNPs) at an air-liquid interface are suitable for long term, non-invasive assessment of ECM remodeling using magnetomotive optical coherence elastography (MMOCE). The morphology of ex vivo CF and normal lung tissues using OCT and correlative study with histology is also examined. We also demonstrate a quantitative measure of normal and CF airway elasticity using MMOCE. The improved understanding of pathologic ...
TY - JOUR. T1 - The cystic fibrosis mutation (ΔF508) does not influence the chloride channel activity of CFTR. AU - Li, Canhui. AU - Ramjeesingh, Mohabir. AU - Reyes, Evangelica. AU - Jensen, Tim. AU - Chang, Xiubao. AU - Rommens, Johanna M.. AU - Bear, Christine E.. PY - 1993/4. Y1 - 1993/4. N2 - The cystic fibrosis transmembrane conductance regulator (CFTR) is a phosphorylation-regulated Ch− channel. In most mammalian cells, the functional consequences of the most common CF mutation, ΔF508-CFTR, cannot be assessed as the mutant protein undergoes biosynthetic arrest. However, function can be studied in the baculovirus-insect cell expression system where ΔF508-CFTR does not appear to undergo such arrest. Our results show that phosphorylation-regulated Cl− channel activity of ΔF508-CFTR is similar to that of wild-type CFTR. This observation was confirmed in comparative studies of purified ΔF508-CFTR and CFTR reconstituted in planar lipid bilayers. Therefore, we suggest that this Common ...
TY - JOUR. T1 - CFTR activation. T2 - Additive effects of stimulatory and inhibitory phosphorylation sites in the R domain. AU - Wilkinson, Daniel J.. AU - Strong, Theresa V.. AU - Mansoura, Monique K.. AU - Wood, Deborah L.. AU - Smith, Stephen S.. AU - Collins, Francis S.. AU - Dawson, David C.. PY - 1997/7. Y1 - 1997/7. N2 - To investigate the functional significance of individual consensus phosphorylation sites within the R domain of cystic fibrosis transmembrane conductance regulator (CFTR), serines were eliminated by substituting them with alanine. Included in this analysis were serine-660, -670, -686, -700, - 712, -737, -768, -795, and -813, which lie within protein kinase A consensus sequences, and serine-641, which does not. Elimination of single potential phosphorylation sites altered the sensitivity of CFTR (expressed in Xenopus oocytes) to activating conditions in a manner that was highly site dependent. Substitution at serine-660, -670, -700, -795, or -813 significantly increased ...
Cystic fibrosis (CF) lung disease is characterized by an inflammatory response that can lead to terminal respiratory failure. The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunctional CFTR in platelets, which are key participants in immune responses, is a central determinant of CF inflammation. We found that deletion of CFTR in platelets produced exaggerated acute lung inflammation and platelet activation after intratracheal LPS or Pseudomonas aeruginosa challenge. CFTR loss of function in mouse or human platelets resulted in agonist-induced hyperactivation and increased calcium entry into platelets. Inhibition of the transient receptor potential cation channel 6 (TRPC6) reduced platelet activation and calcium flux, and reduced lung injury in CF mice after intratracheal LPS or Pseudomonas aeruginosa challenge. CF subjects receiving CFTR modulator therapy showed partial restoration of CFTR function in platelets, which may be a ...
The effects of a thiazolidinone derivative, 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (or CFTRinh-172), on cystic fibrosis transmembrane conductance regulator (CFTR) gating were studied in excised inside-out membrane patches from Chinese hamster ovary cells transiently expressing wild-type and mutant CFTR. We found that the application of CFTRinh-172 results in an increase of the mean closed time and a decrease of the mean open time of the channel. A hyperbolic relationship between the closing rate and [CFTRinh-172] suggests that CFTRinh-172 does not act as a simple pore blocker. Interestingly, the potency of inhibition increases as the open time of the channel is increased with an IC50 in the low nanomolar range for CFTR channels locked in an open state for tens of seconds. Our studies also provide evidence that CFTRinh-172 can bind to both the open state and the closed state. However, at least one additional step, presumably reflecting ...
Author summary Synonymous single nucleotide polymorphisms (sSNPs) occur at high frequency in the human genome and are associated with ~50 diseases in humans; the responsible molecular mechanisms remain enigmatic. Here, we investigate the impact of the common sSNP, T2562G, on cystic fibrosis transmembrane conductance regulator (CFTR). Although this sSNP, by itself, does not cause cystic fibrosis (CF), it is prevalent in patients with CFTR-related disorders. T2562G sSNP modifies the local translation speed at the Thr854 codon, leading to changes in CFTR stability and channel function. This sSNP introduces a codon pairing to a low-abundance tRNA, which is particularly rare in human bronchial epithelia, but not in other human tissues, suggesting a tissue-specific effect of this sSNP. Enhancement of the cellular concentration of the tRNA cognate to the mutant ACG codon rescues the stability and conduction defects of T2562G-CFTR. These findings reveal an unanticipated mechanism-inverting the programmed local
臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。. To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of NTU Repository with Academic Hub to form NTU Scholars.. ...
Трансмембранный регулятор муковисцидоза (англ. CFTR - Cystic Fibrosis Transmembrane conductance Regulator) - белок, участвующий в транспорте ионов хлора через мембрану клетки, а также название гена, кодирующего этот белок. Ген CFTR находится на длинном плече 7-й хромосомы. Мутации в гене CFTR приводят к возникновению заболевания муковисцидоз, а также могут быть причиной мужского бесплодия. Наиболее часто встречается мутация ΔF508 (более 50 % из всех выявляемых мутаций гена), при которой происходит делеция остатка фенилаланина-508 из полипептидной цепочки, что приводит к нарушению ...
J Biol Chem. 1995 Jan 27;270(4):1711-7. Comparative Study; Research Support, Non-U.S. Govt; Research Support, U.S. Govt, P.H.S.
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Teerapuncharoen K; Michael Wells J; Vamsee Raju S; Raraigh KS; Aksit MA; Cutting GR; Rasmussen L; Hrudaya Nath P; Bhatt SP; Solomon GM ...
1CKY: Cystic fibrosis transmembrane conductance regulator: solution structures of peptides based on the Phe508 region, the most common site of disease-causing DeltaF508 mutation.
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EDITOR,-Cystic fibrosis is the most common serious autosomal recessive condition in white populations, affecting about 1 in 2500 live births, and until recently life expectancy rarely exceeded 30 years. The most common cystic fibrosis mutation (δF508, accounting for about 80% of two million British carriers), is a 3-bp deletion in a transmembrane protein cystic fibrosis transmembrane regulator gene. The next most common three or four mutations account for a further 5% of carriers.. One in 25 white people carries cystic fibrosis. As carriers are unaffected, individuals are often unaware until … ...
Many people with cystic fibrosis are counting on cystic fibrosis transmembrane conductance regulator modulators to improve their overall health. Im learning that they have effects I hadnt counted on.
Cystic fibrosis (CF) lung disease is characterized by chronic bacterial colonization and recurrent infection of the airways. Disruption of the cystic fibrosis transmembrane conductance regulator chloride channels in subjects with CF results in altered fluid and electrolyte transport across the airway epithelium thereby initiating infections.. These infections eventually destroy the lungs and contribute to significant morbidity and mortality in patients with CF. It is well known that antibacterial activity of innate immune mediators such as lysozyme and beta defensins in human airway surface liquid (ASL) is salt-sensitive; an increase in salt concentration inhibits their activity.. Conversely, their activity is increased by low ionic strength. Lowering the ASL salt concentration and increasing the ASL volume might therefore potentiate innate immunity and therefore decrease or prevent airway infections in subjects with CF.. Xylitol, a five-carbon sugar with low transepithelial permeability, which ...
Frédéric Velard, Martial Delion, Carole Le Henaff, Christine Guillaume, Sophie Gangloff, et al.. Cystic fibrosis and bone disease: defective osteoblast maturation with the f508del mutation in cystic fibrosis transmembrane conductance regulator.. American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 2014, 189 (6), pp.746-8. ⟨10.1164/rccm.201312-2144LE⟩. ⟨inserm-00965536⟩ ...
Complex alleles in monogenic disease pose a challenge for clinicians because they are often associated with uncommon diagnostic and clinical features. Here we report on the 30 year course of a basic defect and disease in an individual with cystic fibrosis (CF) who was compound heterozygous for the cystic fibrosis transmembrane conductance regulator (CFTR) mutations R553X1 and the complex allele F508del-R553Q.2. The amino acid substitution R553Q resides within the ABC signature motif of CFTR.3 R553Q has been shown in heterologous model systems to partially correct the defective processing and anomalous ion channel gating of mutant F508del CFTR.4 Hence R553Q has been classified as a disease reverting suppressor mutation. Investigation of the affected subject, however, revealed a more complex manifestation of the basic defect of anomalous epithelial chloride conductance.. The sweat test is still the gold standard to diagnose CF5 whereby elevated sweat chloride concentrations of more than 60 mmol/l ...
Cystic Fibrosis (CF) is a progressive autosomal recessive disorder caused by defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR mutations cause loss or impairment of CFTR-mediated ion transport across epithelial cell membranes. CF affects many organs including the respiratory tract, pancreas, intestine, liver and the male reproductive tract. Liver disease occurs less frequently than pulmonary disease. CFTR is expressed in the bile duct epithelial cells and is responsible for the hydration of biliary secretions.. CF was until recently, thought to be a multi-organ disease. However, there are now recognized non-classical presentations of CF involving a few organs only and now there is well established data on single -organ involvement including Congenital Absence of the Vas Deferens and recurrent pancreatitis.. CF and PSC have several features in common. They both affect intrahepatic bile ducts by inspisated biliary secretions, chronic inflammation and fibrosis. Is ...
Ataluren (PTC 124; PTC Therapeutics),18 currently recognized as an orphan drug by the FDA, is a more appealing therapeutic option for class I CFTR defects. In a mechanism similar to the pleiotropic effects of aminoglycosides, ataluren allows ribosomes to read through the mRNA premature stop codons, resulting in the translation of complete CFTR proteins.19,20 Several phase II and III studies19-21 have evaluated this drugs efficacy and demonstrated improvements in nasal transepithelial potential differences, forced expiratory volume in 1 second (FEV1), and weight gain in both adult and pediatric patient populations.20 Adverse effects were generally mild, with gastrointestinal upset, headache, and dizziness most commonly reported (Table 2). Because of its efficacy in targeting the underlying cause of CF and favorable adverse effect profile, ataluren is considered the more appropriate initial approach compared with aminoglycosides in patients with CF who have class I mutations.10,21 Several phase ...
Cystic fibrosis (CF) is a multiorgan progressive genetic disease caused by loss of functional cystic fibrosis transmembrane conductance regulator (CFTR) channel. Previously, we identified a significant dysfunction in CF cells and model mice of the transcription factor nuclear factor E2-related factor-2 (Nrf2), a major regulator of redox balance and inflammatory signaling. Here we report that the approved F508del CFTR correctors VX809 and VX661 recover diminished Nrf2 function and colocalization with CFTR in CF human primary bronchial epithelia by proximity ligation assay, immunoprecipitation, and immunofluorescence, concordant with CFTR correction. F508del CFTR correctors induced Nrf2 nuclear translocation, Nrf2-dependent luciferase activity, and transcriptional activation of target genes. Rescue of Nrf2 function by VX809/VX661 was dependent on significant correction of F508del and was blocked by inhibition of corrected channel function, or high-level shRNA knockdown of CFTR or F508del CFTR. ...
Despite therapeutic advancement, pulmonary disease still remains a major cause of morbidity and mortality around the world. Opportunities to study human lung disease either in vivo or in vitro are currently limited. Using induced pluripotent stem cells (iPSCs), we generated mature multiciliated cells in a functional airway epithelium. Robust multiciliogenesis occurred when notch signaling was inhibited and was confirmed by (i) the assembly of multiple pericentrin-stained centrioles at the apical surface, (ii) expression of transcription factor forkhead box protein J1, and (iii) presence of multiple acetylated tubulin-labeled cilia projections in individual cells. Clara, goblet, and basal cells were all present, confirming the generation of a complete polarized epithelial-cell layer. Additionally, cAMP-activated and cystic fibrosis transmembrane regulator inhibitor 172-sensitive cystic fibrosis transmembrane regulator currents were recorded in isolated epithelial cells. Our report demonstrating ...
Over 1,900 mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein are implicated in causing Cystic Fibrosis (CF). Potential therapies that directly target defective CFTR are being evaluated in important clinical trials, but most target the most common CFTR mutation F508del. Many patients with rare CF mutations are not able to participate in those studies. The RARE study is specifically designed for people with CF caused by rare mutations. Eligible rare mutations are listed below: - CF patients who are homozygous for pre-mature stop codons - CF patients with two mutations in the CFTR gene: i. One allele must be a F508del ii. The other allele must be a pre-mature stop codon mutation - CF patients with two mutations in the CFTR gene: i. At least one allele must be a pre-mature stop codon mutation ii. The second allele can be any of the following: G85E, N1303K, R334W, 3849+10kb C->T, 621+1G->T - CF patients who are homozygous for: G85E, N1303K, R334W, ...
TY - JOUR. T1 - Impaired cardiac and peripheral hemodynamic responses to inhaled β2-agonist in cystic fibrosis. AU - Van Iterson, Erik H.. AU - Karpen, Stephen R.. AU - Baker, Sarah E.. AU - Wheatley, Courtney M.. AU - Morgan, Wayne J.. AU - Snyder, Eric M.. N1 - Publisher Copyright: © 2015 Van Iterson et al. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.. PY - 2015/9/5. Y1 - 2015/9/5. N2 - Background: Pulmonary system dysfunction is a hallmark of cystic fibrosis (CF) disease. In addition to impaired cystic fibrosis transmembrane conductance regulator protein, dysfunctional β2-adrenergic receptors (β2AR) contribute to low airway function in CF. Recent observations suggest CF may also be associated with impaired cardiac function that is demonstrated by attenuated cardiac output (Q), stroke volume (SV), and cardiac power (CP) at both rest and during exercise. However, β2AR regulation of cardiac and peripheral vascular tissue, in-vivo, is unknown in CF. We have previously ...
Plasma membrane Cl- channels perform a variety of functions, including control of excitability in neurons and muscle, cell volume regulation and transepithelial transport. Structurally, three classes of Cl- channels have been identified: ligand-gated, postsynaptic Cl- channels (e.g. GABA and glycine receptors); the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels (which belong to the traffic ATPase superfamily); and the CLC family of Cl- channels. Recent developments of note include further characterization of the expanding CLC Cl- channel family, advances in understanding the regulation of the CFTR Cl- channel and its emergent role as a regulator of other channels, clarification of issues related to swelling-activated Cl- channels, and the discovery that several co-transporter molecules are now known to induce Cl- currents in Xenopus oocytes.. ...
English: What is cystic fibrosis? Cystic fibrosis is an autosomal recessive disorder involving the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which causes complications in the lungs, pancreas, and other organs. This video covers the pathophysiology, signs and symptoms, and treatment for cystic fibrosis. Sources: - Cutting, G. Cystic Fibrosis. In: Emery and Rimoins Principles and Practice of Medical Genetics (Sixth Edition); 2013. - First Aid - ...
Triplet CFTR modulators: future prospects for treatment of cystic fibrosis Nauman Chaudary Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA Abstract: Cystic fibrosis (CF) is an autosomal recessive genetic disease characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a chloride channel responsible for ion flow across epithelial surfaces of lung, sinuses, pancreas, intestine, and liver. Researchers have grouped CFTR genetic mutations into various protein defects: reduced protein synthesis (class 1 mutations), abnormal protein folding and maturation (class 2 mutation), and abnormal gating (class 3 mutation). These mutations usually present as severe forms of CF due to complete absence of CFTR at cell surfaces. Milder forms (eg, protein maturation and conductance defects, classes 4–6) present as less severe forms of CF related to the presence of CFTR at the cell
BACKGROUND Polymorphisms in transforming growth factor (TGF)-β1 associated with variations in cytokine levels are linked to fibrosis in a number of tissues. However, the contribution of this cytokine to organ fibrosis in patients with cystic fibrosis is presently unclear. This study was undertaken to examine the association between TGF-β1 gene polymorphisms and the development of pulmonary dysfunction in patients with cystic fibrosis.. METHODS Polymorphisms in the TGF-β1 gene defining amino acids of codons 10 and 25 were determined by ARMS-PCR using DNA stored on 171 Caucasian patients who were homozygous for the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical information on the patients was obtained from medical records.. RESULTS Patients with cystic fibrosis of a TGF-β1 high producer genotype for codon 10 had more rapid deterioration in lung function than those with a TGF-β1 low producer genotype. The relative risk of accelerated decline in ...
TY - JOUR. T1 - Light and alcohol evoked electro-oculograms in cystic fibrosis. AU - Constable, Paul. AU - Lawrenson, John. AU - Arden, Geoffrey. PY - 2006. Y1 - 2006. N2 - Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) which is a chloride channel. CFTR is expressed in the retinal pigment epithelium (RPE) where it is believed to be important in generating the fast oscillations (FOs) and potentially contributing to the light-electrooculogram (EOG). The role of CFTR in the alcohol-EOG is unknown. We recruited six individuals with CF (three homozygotes for δ508 and three heterozygous for δ508) and recorded the light- and alcohol-EOGs as well as the FOs and compared them to a control group. The results showed that in the CF group the amplitude of the alcohol- and light-EOGs were normal. However, the time to peak of the light- and alcohol-rises were significantly faster than in the control group. We conclude that CFTR is not primarily ...
This antibody recognizes a protein of 165-170 kDa, identified as cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is composed of two membrane-spanning domains (MSD), two nucleotide-binding domains (NBD), and an R domain. It is structurally similar to multidrug resistance (Mdr1) protein and both are members of the superfamily of ATP-binding cassette (ABC) transporters, also known as traffic ATPases, which are implicated in the movement of various substrates. The CFTR protein is a small conductance adenosine 3′,5′-cyclic monophosphate (cAMP)-activated chloride ion channel found in the apical membranes of epithelia within the pancreas, airway, intestine, bile duct, sweat gland, and male genital ducts. CFTR is a valuable marker of human pancreatic duct cell development and differentiation.. Primary antibodies are available purified, or with a selection of fluorescent CF® dyes and other labels. CF® dyes offer exceptional brightness and photostability. See the CF® Dye Brochure ...
The deletion of phenylalanine 508 in the first nucleotide binding site from the cystic fibrosis transmembrane conductance regulator is directly connected with >90% of cystic fibrosis cases. some misfolding and suppressor mutations in the nucleotide binding and transmembrane domains had been evaluated for results for the folding and maturation from the proteins. The outcomes indicate how the isolated NBD1 responds to both ΔF508 mutation and intradomain suppressors of the mutation. Furthermore identification of the book second site suppressor from the defect within the next transmembrane site shows that ΔF508 also results interdomain interactions crucial for later on measures in the biosynthesis of CFTR. folding stability or efficiency. Alternatively they could alter the discussion of CFTR domains while departing the biochemical and biophysical properties from the isolated NBD unaltered. The suppressors may also possess little influence for the properties from the CFTR polypeptide in but may ...
AIM To determine whether pancreatitis associated protein (PAP) is a marker for cystic fibrosis which could be used in neonatal screening for the disease.. METHODS PAP was assayed on screening cards from 202 807 neonates. Babies with PAP ⩾ 15 ng/ml, or ⩾ 11.5 ng/ml and immunoreactive trypsinogen (IRT) ⩾ 700 ng/ml were recalled for clinical examination, sweat testing, and cystic fibrosis transmembrane regulator (CFTR) gene analysis.. RESULTS Median PAP value was 2.8 ng/ml. Forty four cases of cystic fibrosis were recorded. Recalled neonates (n=398) included only 11 carriers. A receiver operating characteristic curve analysis showed that PAP above 8.0 ng/ml would select 0.76% of babies, including all those with cystic fibrosis, except for one with meconium ileus and two with mild CFTR mutations. Screening 27 146 babies with both PAP and IRT showed that only 0.12% had PAP , 8.0 ng/ml and IRT , 700 ng/ml, including all cases of cystic fibrosis.. CONCLUSION PAP is increased in most neonates with ...
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Most diagnoses of CF are made during infancy or childhood, and are based on respiratory or digestive involvement. Initial extracellular dehydration leading to the diagnosis of CF is usual in infants but has only exceptionally been reported in adults. We describe three new adult cases of CF initially presenting with depletive hyponatremia and hypochloremia following exposure to heat. At first consultation, these patients had no symptoms suggestive of CF. One patient presented with a seizure induced by hyponatremia. The two other patients were siblings carrying a novel c.4434insA mutation in exon 24 of CFTR. Acute dehydration is a very rare initial manifestation of CF but may be life-threatening. The possibility of CF should not be ignored in cases of depletive hyponatremia, hypochloremia or hypokalemic metabolic alkalosis, even in otherwise healthy patients.
Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by ...
Approximately 30,000 people in the United States have been diagnosed with CF, which affects both males and females. Its not contagious, so you cant catch CF from another person.. Cystic fibrosis is an inherited disease caused by mutations (changes) in a gene on chromosome 7, one of the 23 pairs of chromosomes that children inherit from their parents. CF occurs because of mutations in the gene that makes a protein called CFTR (cystic fibrosis transmembrane regulator). A person with CF produces abnormal CFTR protein - or no CFTR protein at all, which causes the body to make thick, sticky mucus instead of the thin, watery kind.. People who are born with CF have two copies of the CF gene. In almost all people born with CF, one gene is received from each parent. This means that the parents of kids with CF are usually both CF carriers - that is, they have one normal and one defective gene - but the parents may not have CF themselves because their normal gene is able to take over and make the ...
Background: Nasal potential difference (NPD) test has long been used to assist in the diagnosis of Cystic Fibrosis (CF) and more recently as an outcome measure in clinical trials of new CF therapies. This test has also been adapted to the mouse nose. Objectives: We aimed at evaluating variability of the NPD measurements in CF patients displaying two severe CFTR mutations and in sex-matched healthy controls. NPD recorded from F508del-CF and normal wild-type mice were also compared. Methods and results: In each setting, tests were performed by a single qualified operator. In the clinical setting, the latest standardized operation protocol of the CF foundation was followed. A total of 80 tracings were obtained from 10 patients (23.2 y; range 14 to 32) and 10 healthy subjects (34 y; range 24 to 53), each tested twice, in both nostrils. Two CF and two controls were excluded from the statistical data analysis due to the presence of a single non interpretable NPD tracing (4/80, 5%). To achieve equal sample
Cystic fibrosis is one of the more common life-limiting genetic diseases in South Africa. It is caused by the inheritance of at least two mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is found in all of South Africas diverse population groups.
Cystic Fibrosis Overview What is cystic fibrosis? Cystic fibrosis (CF) is an inherited disease characterized by an abnormality in the bodys salt, water- and mucus-making cells. It is chronic, progressive, and is usually fatal. In general, children with CF live into their 30s. Children with CF have an abnormality in the function of a cell protein called the cystic fibrosis transmembrane regulator (CFTR). CFTR controls the flow of water and certain salts in and out of the bodys cells. As the movement of...
Title:Rescuing Mutant CFTR: A Multi-task Approach to a Better Outcome in Treating Cystic Fibrosis. VOLUME: 19 ISSUE: 19. Author(s):Margarida D. Amaral and Carlos M. Farinha. Affiliation:BioFiG - Center for Biodiversity, Functional and Integrative Genomics, Department of Chemistry & Biochemistry, Faculty of Sciences, University of Lisboa, Campo Grande, C8 bdg, 1749-016 Lisboa, Portugal.. Keywords:Cystic fibrosis, F508del-CFTR, rescue, correctors, potentiators, endoplasmic reticulum retention, traffic mutant, misfolding protein.. Abstract:Correcting multiple defects of mutant CFTR with small molecule compounds has been the goal of an increasing number of recent Cystic Fibrosis (CF) drug discovery programmes. However, the mechanism of action (MoA) by which these molecules restore mutant CFTR is still poorly understood, in particular of CFTR correctors, i.e., compounds rescuing to the cells surface the most prevalent mutant in CF patients - F508del-CFTR. However, there is increasing evidence that to ...
Mature three-spined stickleback males use spiggin threads secreted from their kidney to glue together nest material. This requires strongly hypertrophied renal proximal tubular cells, which compromises renal osmoregulatory function during the breeding period. Experimental evidence suggests that the intestine takes over hypotonic fluid secretion at that stage but the mechanism is unexplored. To unravel the molecular mechanism we analyzed and compared transcript levels of several membrane proteins involved in water and salt transport in intestinal and renal tissues, in non-mature males (NM), mature males (MM), and mature females (MF). Aquaporin paralogs aqp1a, -30, -8aa, -8ab, -10a, and -10b, two Na+,K+-ATPase alpha-1 subunit isoforms (nka547, nka976), Na+,K+,2C1(-)-, and Na+,CI--cotransporters (nkcc1a, nkcc2,ncc), the cystic fibrosis transmembrane conductance regulator (cftr) and two claudin isoforms (cldn2, cldn15a) were expressed in the intestine and kidney in all groups. There were no ...
TY - JOUR. T1 - A cluster of cystic fibrosis mutations in exon 17b of the CFTR gene. T2 - A site for rare mutations. AU - Mercier, B.. AU - Lissens, W.. AU - Novelli, G.. AU - Kalaydjieva, L.. AU - De Arce, M.. AU - Kapranov, N.. AU - Canki Klain, N.. AU - Estivill, Xavier P.. AU - Palacio, Ana. AU - Cashman, S.. AU - Savov, A.. AU - Audrézet, M. P.. AU - Dallapicolla, B.. AU - Liebaers, I.. AU - Quéré, I.. AU - Raguénès, O.. AU - Verlingue, C.. AU - Férec, C.. PY - 1994/9. Y1 - 1994/9. N2 - Intensive screening has improved our understanding of the profile of mutations in the CFTR gene in which more than 400 mutations have been detected to date. In collaboration with several European laboratories we are involved in such analysis. We have identified 14 new mutations in exon 17b of CFTR, having analysed 780 CF chromosomes, and have compared the frequency of mutations in this exon with that of other regions of the CFTR gene. The results obtained indicate an accumulation of mutations, not only ...
Welcome to the Cystic Fibrosis Mutation Database (CFTR1), devoted to the collection of mutations in the CFTR gene for the international cystic fibrosis genetics research community. It was initiated by the Cystic Fibrosis Genetic Analysis Consortium in 1989 to increase and facilitate communications among CF researchers, and is maintained by the Cystic Fibrosis Centre at the Hospital for Sick Children in Toronto. The specific aim of the database is to provide up to date information about individual mutations in the CFTR gene. In a major upgrade in 2010, all known CFTR mutations and sequence variants have been converted to the standard nomenclature recommended by the Human Genome Variation Society. In addition, an on-line process for the submission of new mutations has been added. While we will continue to ensure the quality of the data, we urge the international community to give us feedback and suggestions. Please send email to cftr.admin ...
The Cystic Fibrosis Foundation estimates there are over 30,000 Americans with cystic fibrosis. This disease affects mostly Caucasians whose ancestors came from northern Europe. It affects all racial and ethnic groups but white Caucasians are more at risk for developing or being a carrier of the defective gene that carries cystic fibrosis.. Average lifespan of a patient diagnosed with cystic fibrosis is 30 years. New technology and scientific advances are making life better and improving predictions of life spans for cystic fibrosis patients.. Cystic fibrosis has the following signs and symptoms but will be different for each individual patient. Patients with cystic fibrosis are often diagnosed before the age of three but diagnoses have been given to teens and adults also. One of the symptoms of cystic fibrosis is a delay in the onset of puberty.. Your teen may experience frequent stomach pain, excessive gas, and be late in entering puberty. Other signs and symptoms of cystic fibrosis are ...
Proteins encoded by best1 to -3 genes are implicated as molecular correlates of calcium-activated chloride channels in epithelia. In this issue of Circulation Research, Matchkov et al present compelling evidence that best-3 expression is essential for the generation of calcium-sensitive cGMP-dependent chloride channels in rat mesenteric artery.1. Chloride channels are enigmatic beasts. Numerous phenotypes exist, as determined by their mode of activation, channel kinetics, and pore properties, but the molecular identity has only really been identified for the voltage-dependent Cl− channels (CLCs) and the cAMP-dependent, cystic fibrosis transmembrane regulator (CFTR) channels. For the other types of Cl− channels, there is far less certainty about the molecular identity. Many candidates for the swelling-activated Cl− channel have been promulgated that ultimately have been repudiated.2 Similarly, the molecular identity of the Ca2+-gated Cl− channel, common to vascular smooth muscle cells, ...
A clinical program to assess whether lipid GL67A-mediated gene transfer can ameliorate cystic fibrosis (CF) lung disease is currently being undertaken by the UK CF Gene Therapy Consortium. We have evaluated GL67A gene transfer to the murine nasal epithelium of wild-type and CF knockout mice to assess this tissue as a test site for gene transfer agents. The plasmids used were regulated by either (1) the commonly used short-acting cytomegalovirus promoter/enhancer or (2) the ubiquitin C promoter. In a study of approximately 400 mice with CF, vector-specific CF transmembrane conductance regulator (CFTR) mRNA was detected in nasal epithelial cells of 82% of mice treated with a cytomegalovirus-plasmid (pCF1-CFTR), and 62% of mice treated with an ubiquitin C-plasmid. We then assessed whether CFTR gene transfer corrected a panel of CFTR-specific endpoint assays in the murine nose, including ion transport, periciliary liquid height, and ex vivo bacterial adherence. Importantly, even with the comparatively large
Toronto, ON, Feb. 27, 2019 (GLOBE NEWSWIRE) - MaRS Innovation announced today the concurrent launch of two new LAB150 projects. These projects build on breakthroughs in disease-focused scientific research by prominent teams at The Hospital for Sick Children (SickKids) and the University of Toronto, both of which are Members of MaRS Innovation. LAB150 is a partnership between MaRS Innovation and Evotec AG with the goal of accelerating academic research towards commercial outcomes by providing funding and access to pharmaceutically validated platforms and expertise.. The SickKids project aims to develop novel therapeutics to treat cystic fibrosis (CF), a debilitating and life-shortening rare disorder caused by mutations in a single gene, termed the CF Transmembrane Conductance Regulator (CFTR). The project arose from the extensive decade-long research program at SickKids involving Canadian and international CF patient populations. Led by SickKids senior scientists, Drs. Lisa Strug, Johanna Rommens ...
According to previous reports, flavonoids and nutraceuticals correct defective electrolyte transport in cystic fibrosis (CF) airways. Traditional medicinal plants from China and Thailand contain phytoflavonoids and other bioactive compounds. We examined herbal extracts of the common Thai medicinal euphorbiaceous plant Phyllanthus acidus for their potential effects on epithelial transport. Functional assays by Ussing chamber, patch-clamping, double-electrode voltage-clamp and Ca2+ imaging demonstrate activation of Cl- secretion and inhibition of Na+ absorption by P. acidus. No cytotoxic effects of P. acidus could be detected. Mucosal application of P. acidus to native mouse trachea suggested transient and steady-state activation of Cl- secretion by increasing both intracellular Ca2+ and cAMP. These effects were mimicked by a mix of the isolated components adenosine, kaempferol, and hypogallic acid. Additional experiments in human airway cells and CF transmembrane conductance regulator ...
The findings in Figure 6C are the first to show regulation of native CFTR activity by any transporter and the combined results show that deletion of slc26a6 resulted in dis-regulation of CFTR in the pancreatic duct. Slc26a6 inhibits the activity of CFTR in the resting state, which likely prevents unnecessary fluid and HCO3− secretion. This is evident from the increased HCO3− permeability and fluid secretion in slc26a6−/− ducts that is eliminated by knock-down of CFTR. In addition, we showed previously that the pancreatic (Ahn et al, 2001) and salivary ducts (Luo et al, 2001; Park et al, 2002) express the HCO3− salvage mechanisms NHE3 and NBC3 that are active in the resting state and are inhibited by CFTR at the stimulated state (Ahn et al, 2001; Luo et al, 2001; Park et al, 2002). On the other hand, CFTR does not seem to regulate slc26a6 activity in the resting state because CFTRinh-172 and knock-down of CFTR did not reduce Cl−/HCO3− exchange activity of the unstimulated duct ...
Congenital Absence of Thigh and Lower Leg with Foot Present (Congenital Bilateral Absence of Thigh and Lower Leg with Foot Present): Read more about Symptoms, Diagnosis, Treatment, Complications, Causes and Prognosis.
Congenital Bilateral Absence of Vas Deferens (Congenital Bilateral Agenesis of Vas Deferens): Read more about Symptoms, Diagnosis, Treatment, Complications, Causes and Prognosis.
Scientific experiments examining what happens to the faulty channel protein that causes cystic fibrosis during inflammation have yielded unexpected and exciting results. The study, conducted by Sara Bitam and her colleagues at INSERM in France, has just passed peer review on open science publishing platform F1000Research (http://f1000research.com/articles/4-218/v2).. Cystic fibrosis is a life-limiting auto. ...
Description of disease Cystic fibrosis. Treatment Cystic fibrosis. Symptoms and causes Cystic fibrosis Prophylaxis Cystic fibrosis
Presented to the AACT 2015 Conference. Cystic fibrosis (CF) is an inherited, fatal disease in which the cystic fibrosis transmembrane receptor (CFTR) gene is mutated, resulting in a defective CFTR sodium-chloride pump. Inefficient CFTR results in a dysregulated balance of sodium and chloride ions across membranes, causing an increase mucous viscosity and susceptibility to gastrointestinal obstruction, pancreatic insufficiency, ultimately leading to failure to thrive. Clinically, major strides have been made in caring for individuals with CF allowing management of many of the clinical issues associated with CF, extending life expectancy into the third trimester. However, despite new developments in small molecule correctors and CFTR expression enhancers, which work at the CFTR defect itself, pulmonary bronchiectasis, bacterial colonization and the ensuing inflammatory response continue to contribute to lung congestion, pulmonary failure, decreased quality of life and death in CF patients. Human ...
We would like to report to the consortium one novel mutation located in exon 20 of the CFTR gene and one novel sequence variation located in exon 2 of the CFTR gene. The missense mutation was detected by DGGE and identified by direct sequencing. The mutation S1255L (C-,T at 3896) is not found in 200 other non-[delta]F508 CF chromosomes and 200 non CF chromosomes tested. Two other CF mutations have been identified at the same codon ...
The study group consisted of five patients diagnosed with cystic fibrosis based on the presence of clinical symptoms characteristic for the disease.1 All patients were compound heterozygotic for ΔF508 (1652del3, exon 10) and R553X (1789C→T) mutations. Control samples were obtained from healthy individuals and did not carry CFTR mutations. The study was approved by the Human Subjects Review Board of The Hospital for Sick Children.. Total RNA was extracted from cultured lymphoblastoid cells treated with cycloheximide (100 μg/ml in DMSO) or DMSO only for 4 h before harvesting, using RNeasy extraction kit (Qiagen). First strand cDNA was synthesised from 2-3 μg of total RNA by oligo-dT-primed reverse transcription with superscript II reverse transcriptase (Invitrogen) according to the suppliers directions. A PCR was then performed to generate a fragment spanning exons 10, 11 and 12 of the CFTR transcript using primers X10-5, 5′-GAG GGT AAA ATT AAG CAC AG-3′ and X12-3s, 5′-AGG TAT CCA AAA ...
The goal of this cystic fibrosis continuing education module is to help nurses, physicians, and physical therapists gain a deeper understanding of cystic fibrosis and the treatments available, as well as to become informed about the latest research. After studying the information presented here, you will be able to: Describe the basic defect that causes cystic fibrosis and how it affects different organ systems Identify three therapies for the management of pulmonary and GI disease in patients with cystic fibrosis Explain teaching and support responsibilities Discuss research and the future of cystic fibrosis     Accreditation Information   This course is intended for multiple professions, including nurses, physicians and physical therapists.   Physical therapists: Take this version of the course to ensure you receive appropriate credit.   For the version accredited or approved for another profession, go to your specific profession at
Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people worldwide. CF is a progressive, multi-system disease that affects the lungs, liver, GI tract, sinuses, sweat glands, pancreas and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes - one from each parent - to have CF. While there are many different types of CFTR mutations that can cause the disease, the vast majority of all people with CF have at least one F508del mutation. These mutations, which can be determined by a genetic test or genotyping test, lead to CF by creating non-working and/or too few CFTR proteins at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung ...
MONDAY, Aug. 26 (HealthDay News) -- Researchers who identified 105 new genetic mutations that cause cystic fibrosis say their findings will improve diagnosis and could increase the number of patients who receive individualized drug treatment.. Cystic fibrosis is a genetic disorder that causes a buildup of thick mucus in the lungs, resulting in frequent lung infections, breathing problems and decreased lung function. Eventually, the repeated infections destroy the lungs.. More than 1,900 mutations had already been identified in the gene responsible for cystic fibrosis, but it was unclear how many of them actually contribute to the disease.. In this study, researchers analyzed genetic information from nearly 40,000 cystic fibrosis patients in order to determine which of the 1,900 mutations are benign and which are harmful. Their findings increased the number of mutations known to cause cystic fibrosis from 22 to 127.. The study was published online Aug. 25 in the journal Nature ...
According to the Associated Press, Cystic Fibrosis treatment include inhaled medications and a chest - vibrating vest to clear airway clogs. The Cystic Fibrosis disease causes a mucus to build up in the lungs, clogging them and leading to life-threatening infections. That same mucus also clogs the pancreas so the body cant properly digest food. Cystic Fibrosis generally showed up in kids, who didnt make it to become adults. But whats happening now is that Cystic Fibrosis is showing up in people later in life. Whats found is that proper care leads to longer life, but theres something the AP article does not address. The impact of the non-smoking movement. Not discussed is the impact of the non-smoking movement on Cystic Fibrosis patients. Its wildly known that smoking can harm Cystic Fibrosis patients, but not talked about is the impact of the non-smoking movement and the attack on the spread of second-hand smoke. Also not considered is the impact of the diet and vitamins movement. Also, ...
This program explains Cystic Fibrosis. Cystic Fibrosis is also known as CF. The program includes the following sections: what is cystic fibrosis, what are the causes of cystic fibrosis, what are the symptoms of cystic fibrosis, how is cystic fibrosis diagnosed, what are treatment options for cystic fibrosis, and what are facts about cystic fibrosis.
Over 700 runners took part in the 16th annual Narberth Cystic Fibrosis Run on Saturday, April 21. The five-mile run followed a certified course around Narberth. The Narberth Cystic Fibrosis Run raises money to help make wishes come true for kids with cystic fibrosis. Cystic fibrosis is an inherited, chronic disease that wreaks havoc on the lungs and digestive system, and for which there is no cure. Organized by siblings Ame Austin, Molly McBryan and Matt McCloskey, who has cystic fibrosis, the mission of the Narberth Cystic Fibrosis Run is simple: to fulfill the wishes and dreams of children living with cystic fibrosis and give them respite from the daily turmoil inflicted by this disease. Since the Runs inception, it has fulfilled more than 80 wishes of children living with cystic fibrosis ...
New advances in cystic fibrosis medical research announced in June have been welcomed by the Cystic Fibrosis Trust as it stands to benefit up to half of all people living with cystic fibrosis in the UK.. The results, released by Vertex Pharmaceuticals Ltd, of a phase III trial for a new treatment for people with cystic fibrosis aged 12 and over with two copies of the F508del mutation, demonstrate that a combination of the drugs ivacaftor and lumacaftor could offer additional treatment to address the underlying cause of the disease and increase lung capacity.. Janet Allen, Director of Care and Research for the Cystic Fibrosis Trust said: We are pleased to see these promising results, which open up a new front in the fight against cystic fibrosis. This new combination therapy looks set to be an important additional treatment option that could improve the lives of many people with cystic fibrosis. As this leading edge of science continues to be explored and better understood, we are hopeful that a ...
The U.S. Food and Drug Administration approved a cystic fibrosis medication that is the first triple-combination therapy available to treat patients 12 and older who have the most common cystic fibrosis mutation, and medical professionals say it has the potential to treat up to 90 percent of all cystic fibrosis patients.
Ann Arbor-based NanoBio Corp. announced Thursday at a medical conference that it got encouraging data from preclinical studies that one of its products was able to kill highly drug-resistant forms of bacteria commonly found in cystic fibrosis patients. The results were presented at the annual North American Cystic Fibrosis Conference in Minneapolis. Cystic fibrosis patients are susceptible to respiratory failure after repeated bacterial infections of the lungs.
Acute myeloid leukemia (AML) accounts for approximately 15-20% of all childhood leukemias, and despite dramatic improvements in treatment outcome, only approximately 70% of children with AML are cured.1 AML results from collaborating genetic aberrations in at least 2 different classes; type-I aberrations, inducing uncontrolled cell proliferation and/or survival, and type-II aberrations inhibiting cell differentiation. However, certain aberrations found in AML do not completely fit into our current definition of type-I and type-II aberrations.2 These aberrations concern epigenetic modifier genes involved in DNA methylation and histone modification, such as Ten-Eleven Translocation 2 (TET2), Isocitrate Dehydrogenase 1 (IDH1), IDH2, Enhancer of Zeste Homolog 2 (EZH2), DNA (cytosine-5)-Methyltransferase 3 Alpha (DNMT3A) and Additional Sex Combs Like-1 (ASXL1). Most of these genes are frequently mutated in adult AML patients with a prevalence varying between 12% to 35% per gene.3-7 Reports on ...
19 % of the CFTR protein make up the twelve transmembrane domains (M1 - M12). These domains have been shown to be comprised of typical a-helical secondary structure. Many of the residues within these regions form the channel lining residues and have a major role in the regulation of pore function. Six positively charged residues within the transmembrane domains [K95 (M1), R134 (M2), R334 (M6), K335 (M6), R347 (M6) and R1030 (M10] that are well conserved across species. Two of these are associated with mutations causing CF, R334Q/W and R347C/H/L/P ...
"Phosphorylation of the cystic fibrosis transmembrane conductance regulator". The Journal of Biological Chemistry. 267 (18): ... "Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure". Nature Medicine. 9 (12): ... "cGMP-dependent protein kinase I beta physically and functionally interacts with the transcriptional regulator TFII-I". The ...
For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, and ... "The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability". Cellular and Molecular Life Sciences. 74 (1 ...
Discovery of the cystic fibrosis trans-membrane conductance regulator gene. The New Zealand Department of Conservation begins ... "Identification of the cystic fibrosis gene: chromosome walking and jumping". Science. 8 September 1989. Retrieved 30 October ...
Fischer H, Schwarzer C, Illek B (2004). "Vitamin C controls the cystic fibrosis transmembrane conductance regulator chloride ...
2006). "Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator". Cell. 126 ...
The gene responsible for the cystic fibrosis transmembrane conductance regulator was discovered. Mutations of the gene are ... considered causes of cystic fibrosis. The kakapo, a bird species of New Zealand, was termed a threatened species. The ...
"MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene". Biochemical Journal. 438 (1 ...
... channel 3 and cystic fibrosis transmembrane conductance regulator". J. Biol. Chem. 281 (48): 36960-8. doi:10.1074/jbc. ... 2 hydrophobic transmembrane (TM) regions, and a large extracellular loop, which has many cysteine residues with conserved ...
Linsdell P, Hanrahan JW (November 1996). "Disulphonic stilbene block of cystic fibrosis transmembrane conductance regulator Cl ... Linsdell P (February 2014). "Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, ... Cystic fibrosis is a progressive, genetic disease that is linked to CF transmembrane regulator (CFTR) dysfunction. Blockage of ... Cystic Fibrosis transmembrane regulators (CFTRs) function in chloride ion, bicarbonate anion, and fluid transport. They are ...
... has been shown to interact with the cystic fibrosis transmembrane conductance regulator. Mutations in this gene may ... 2006). "Cysteine string protein monitors late steps in cystic fibrosis transmembrane conductance regulator biogenesis". J. Biol ... "Cysteine string protein interacts with and modulates the maturation of the cystic fibrosis transmembrane conductance regulator ... It is known to play a role in cystic fibrosis and Huntington's disease. This protein has been proposed as a key element of the ...
"Regulation of the cystic fibrosis transmembrane conductance regulator ClK channel by its R domain". Journal of Biological ... aeruginosa to persist in the cystic fibrosis lung; it is often detected in the sputum from cystic fibrosis patients. Pyocyanin ... In the cystic fibrosis lung, intracellular pyocyanin converts molecular oxygen to the superoxide free radical by oxidizing ... Pseudomonas aeruginosa Cystic fibrosis Pyocyanin at Sigma-Aldrich Hassan H & Fridovich I (1980). "Mechanism of the antibiotic ...
CFTR (cystic fibrosis transmembrane conductance regulator) is a membrane protein and chloride channel in vertebrates. CFTR may ...
Cystic fibrosis caused by the G542X mutation in the cystic fibrosis transmembrane conductance regulator gene). rs6311 and ... β-thalassemia and cystic fibrosis result from SNPs. The severity of illness and the way our body responds to treatments are ... "Cystic fibrosis patients bearing both the common missense mutation Gly----Asp at codon 551 and the delta F508 mutation are ...
It is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The product of this gene ... The name cystic fibrosis refers to the characteristic 'fibrosis' (tissue scarring) and cyst formation within the pancreas, ... Cystic fibrosis, is a hereditary disease that affects the entire body, causing progressive disability and early death. ... EPI is found in humans afflicted with cystic fibrosis and Shwachman-Diamond syndrome. It is caused by a progressive loss of the ...
"Syntaxin 8 impairs trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits its channel activity ... "Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in ... McShea A, Samuel T, Eppel JT, Galloway DA, Funk JO (Jul 2000). "Identification of CIP-1-associated regulator of cyclin B (CARB ...
CO2 metabolism Enters through membrane-transporting proteins or cystic fibrosis transmembrane conductance regulators. Calcium ... sAC differentiates from the transmembrane adenylyl cyclase (tmACs) - an important source of cAMP; in that sAC is regulated by ... Bone density experiments in mouse calvaria cultured indicates that HCO−3-sensing sAC is a physiological appropriate regulator ... and regulators, reveal a generic Class III AC architecture with sAC-specific features. The structurally related domains C1 and ...
2005). "Interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) inhibits beta1-adrenergic ... Cystic fibrosis transmembrane conductance regulator and CSPG5. GRCh38: Ensembl release 89: ENSG00000047932 - Ensembl, May 2017 ... Cheng J, Wang H, Guggino WB (2004). "Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ domain ... chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator- ...
... such as the cystic fibrosis transmembrane conductance regulator (CFTR), and P-glycoprotein by interfering with the host ... "Crystal structure of the cystic fibrosis transmembrane conductance regulator inhibitory factor Cif reveals novel active-site ... Secreted Protein PA2934 Decreases Apical Membrane Expression of the Cystic Fibrosis Transmembrane Conductance Regulator". ... By promoting the ubiquitin-mediated degradation of CFTR, Cif is able to phenocopy cystic fibrosis at the cellular level. The ...
2007). "Molecular characterization of the cystic fibrosis transmembrane conductance regulator gene in congenital absence of the ... "The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel". J. Pediatr. 132 (4): 589- ... There are two main populations of CAVD; the larger group is associated with cystic fibrosis and occurs because of a mutation in ... Strikingly, CAVD is one of the most consistent features of cystic fibrosis as it affects 98-99% of individuals in this CF ...
... regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator". ...
"Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic ... October 2003). "Allergic bronchopulmonary aspergillosis in cystic fibrosis-state of the art: Cystic Fibrosis Foundation ... ABPA should be suspected in patients with a predisposing lung disease-most commonly asthma or cystic fibrosis- and is often ... In people with predisposing lung diseases-such as persistent asthma or cystic fibrosis (or rarer diseases such as chronic ...
CF is caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In ... The aminoglycoside gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory to induce them to grow full- ... Pai VB, Nahata MC (October 2001). "Efficacy and safety of aerosolized tobramycin in cystic fibrosis". Pediatr. Pulmonol. 32 (4 ... 2003). "Gentamicin-Induced Correction of CFTR Function in Patients with Cystic Fibrosis andCFTRStop Mutations". New England ...
... inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator". ...
2000). "Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP- ...
... is a specific mutation within the gene for a protein called the cystic fibrosis transmembrane conductance regulator (CFTR). The ... One gene for cystic fibrosis is sufficient to produce mild lung abnormalities even in the absence of infection. Cystic fibrosis ... "Molecular biology of cystic fibrosis: CFTR processing and functions, and classes of mutations". Cystic fibrosis (3rd ed.). ... Approximately 70% of cystic fibrosis cases in Europe are due to homozygous ΔF508 mutations (this varies widely by region). The ...
2007). "Derlin-1 promotes the efficient degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR ... a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 ...
... with cystic fibrosis who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator ( ... "VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane- ... people who have two copies of the F508del mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator ... "FDA approves new treatment for cystic fibrosis". United States Food and Drug Administration. July 2, 2015. Wasserman, Emily ( ...
... in the biogenesis of the cystic fibrosis transmembrane conductance regulator". The Journal of Biological Chemistry. 269 (17): ... a single transmembrane helix and a short (90 residues), acidic cytoplasmic tail. Calnexin is a chaperone, characterized by ...
... by cystic fibrosis transmembrane conductance regulator co-expression in Xenopus oocytes". J. Biol. Chem. 277 (10): 8395-405. ... 2 hydrophobic transmembrane (TM) regions, and a large extracellular loop, which has many cysteine residues with conserved ... "Malignant human gliomas express an amiloride-sensitive Na+ conductance". Am. J. Physiol. 276 (6 Pt 1): C1405-10. PMID 10362604 ...
P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory ... Cystic fibrosis transmembrane conductance regulator and PLCB3. Solute carrier family GRCh38: Ensembl release 89: ... "E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in ... "E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in ...
... "cystic fibrosis transmembrane conductance regulator"). Tento objav viedol k hypotéze, že nositelia génu pre cystickú fibrózu sú ... Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science, október 1994, roč. 266, ... The genetic advantage hypothesis in cystic fibrosis heterozygotes: a murine study. The Journal of Physiology, január 1995, roč ... Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that ...
Cystic fibrosis is an autosomal recessive disorder involving the cystic fibrosis transmembrane conductance regulator (CFTR) ... DescriptionCystic fibrosis.webm. English: What is cystic fibrosis? ... and treatment for cystic fibrosis. Sources: - Cutting, G. Cystic Fibrosis. In: Emery and Rimoin's Principles and Practice of ...
... specialized cells in the lung called pulmonary ionocytes that express the Cystic Fibrosis Transmembrane Conductance Regulator ...
... the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria ... The cystic fibrosis genetic mutation known as delta-F508 in humans has been said to maintain a selective heterozygous advantage ... Bertranpetit J, Calafell F (1996). "Genetic and geographical variability in cystic fibrosis: evolutionary considerations". Ciba ... who are thus not affected by cystic fibrosis) are more resistant to V. cholerae infections.[25] In this model, ...
"Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease 11 (11): ... "Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease". ... cystic fibrosis transmembrane conductance regulator mRNA ameliorates the severity of pulmonary disease in cystic fibrosis". Am ... "An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton". J. Biol. Chem. 273 ...
In the cystic fibrosis transmembrane regulator (CFTR) and in the sulfonylurea receptor (SUR), ATP hydrolysis is associated with ... 3.A.1.202 The Cystic Fibrosis Transmembrane Conductance Exporter (CFTR) Family (ABCC) 3.A.1.203 The Peroxysomal Fatty Acyl CoA ... CFTR, the transporter involved in the disease Cystic Fibrosis, is also considered part of this subfamily. Cystic fibrosis ... Some of these exporters in humans are involved in tumor resistance, cystic fibrosis and a range of other inherited human ...
... such as the cystic fibrosis transmembrane conductance regulator (CFTR).[8] Interactions[edit]. Farnesoid X receptor has been ... role for the bifunctional apoptosis regulator protein". The Journal of Biological Chemistry. 277 (6): 4351-60. doi:10.1074/jbc. ... "Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis". Acta Pharmacologica Sinica. 36 (1 ...
Cystic fibrosis transmembrane conductance regulator. ». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۸ اکتبر ۲۰۱۷. ... CFTR با عنوانِ کاملِ «تنظیم‌کنندهٔ هدایت تراغشایی فیبروز سیستیک» (انگلیسی: Cystic fibrosis transmembrane conductance regulator ... CFTR, ABC35, ABCC7, CF, CFTR/MRP, MRP7, TNR-dJ760C5.1, cystic fibrosis transmembrane conductance regulator. ... Cystic Fibrosis Mutation Database. "Genomic DNA sequence".. *↑ Kavic SM, Frehm EJ, Segal AS (1999). "Case studies in cholera: ...
Трансмембранный регулятор муковисцидоза (англ. CFTR - Cystic Fibrosis Transmembrane conductance Regulator) - белок, участвующий ... P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory ... The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3- salvage ... An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton (англ.) // Journal of ...
Secretin and VIP act to increase the opening of the cystic fibrosis transmembrane conductance regulator, which leads to more ... cotransporter that acts because of membrane depolarisation caused by the cystic fibrosis transmembrane conductance regulator. ... with other causes including recurrent acute episodes and cystic fibrosis. Abdominal pain, characteristically relieved by ... 1. Bile ducts: 2. Intrahepatic bile ducts, 3. Left and right hepatic ducts, 4. Common hepatic duct, 5. Cystic duct, 6. Common ...
... cystic fibrosis transmembrane conductance regulator) protein, then their children have a 25% of inheriting the disease.[23] If ... Cystic Fibrosis[edit]. Cystic Fibrosis is an autosomal recessive disorder that causes a variety of symptoms and complications, ... "Johns Hopkins Cystic Fibrosis Center. Retrieved 23 September 2018.. *^ a b c d e f Sander JD, Joung JK (April 2014). "CRISPR- ... "Cystic Fibrosis Canada". www.cysticfibrosis.ca. Retrieved 2017-11-30.. *^ O'Sullivan BP, Freedman SD (May 2009). "Cystic ...
Cystic fibrosis (caused by the G542X mutation in the cystic fibrosis transmembrane conductance regulator gene). ... Emily's Entourage, a cystic fibrosis nonprofit researching point-nonsense mutations. External links and references[edit]. *^ ... "Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial" ...
CF is caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In ... Pai VB, Nahata MC (October 2001). "Efficacy and safety of aerosolized tobramycin in cystic fibrosis". Pediatr. Pulmonol. 32 (4 ... 2003). "Gentamicin-Induced Correction of CFTR Function in Patients with Cystic Fibrosis andCFTRStop Mutations". New England ... The aminoglycoside gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory to induce them to grow full- ...
Cystic fibrosis transmembrane conductance regulator. *Cytochrome c. *DCTN1. *DOK1. *Dysferlin. *ETV6. *EZH2 ...
... consensus of the NHE-RF-PDZ1 domain matches the C-terminal sequence of cystic fibrosis transmembrane conductance regulator ( ... YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcriptional regulator by ... "Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β Pathways". Structure. 20 (10): ...
These active PKA then phosphorylate the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel proteins, ...
... acrónimo de Cystic fibrosis transmembrane conductance regulator (regulador de la conductancia transmembrana de la fibrosis ... causada por una proteína anormal CFTR (Cystic fibrosis transmembrane conductance regulator), la cual no permiten el ingreso y ... Hodgkin, A.L.; Huxley, A.F. (1952) The components of membrane conductance in the giant axon of Loligo. (6.9MB) J. of Physiology ... J Grassl Soc South Afr 9(2). Smith, S. E., et a. (2006). Epidermal conductance as a component of dehydration avoidance in ...
Molecular characterization of the cystic fibrosis transmembrane conductance regulator gene in congenital absence of the vas ... Childers M, Eckel G, Himmel A, Caldwell J (2007). „A new model of cystic fibrosis pathology: lack of transport of glutathione ... Gadsby DC, Vergani P, Csanády L (2006). „The ABC protein turned chloride channel whose failure causes cystic fibrosis". Nature ... Identification of the cystic fibrosis gene: chromosome walking and jumping". Science. 245 (4922): 1059-65. Bibcode:1989Sci... ...
Cystic fibrosis transmembrane conductance regulator)上的突變並不是導致瀰漫性泛細支氣管炎的因素,但是已知這個基因有一種特殊的多態性(變異),它會出現在不少沒有患上這兩種病的亞洲人身上。現時研究正在調查這 ... 鐵釩土纖維化(英语:Bauxite fibrosis). 鈹肺病(英语:Berylliosis). 類風濕塵肺綜合症(英语:Caplan's syndrome). 石末肺(英语:Chalicosis). 煤礦工人肺塵病(英语
"Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis". Curr Opin ... drug used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator ... cystic fibrosis in people having one of several specific mutations in the cystic fibrosis transmembrane conductance regulator ( ... "Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of ...
Cystic fibrosis-like syndrome with normal cystic fibrosis transmembrane conductance regulator (CFTR) protein levels 2) ... Thus, loss of the function of CAXII in sweat glands and lungs is the molecular basis for cystic fibrosis patients with normal ... Quinton, PM (December 2010). "Role of epithelial HCO3⁻ transport in mucin secretion: lessons from cystic fibrosis". American ... Ivanov SV, Kuzmin I, Wei MH, Pack S, Geil L, Johnson BE, Stanbridge EJ, Lerman MI (1998). "Down-regulation of transmembrane ...
1998). "The mechanism underlying cystic fibrosis transmembrane conductance regulator transport from the endoplasmic reticulum ...
... in patients with certain mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene (primarily the G551D ... Commissioner, Office of the (2020-03-24). "FDA approves new breakthrough therapy for cystic fibrosis". FDA. Retrieved 2020-07- ... "Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations". MDLinx. Retrieved 2020- ... "Ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation". European Respiratory Review. 22 (127): 66-71 ...
... mainly by way of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel activation. This results in increased ...
... is a medication that acts as cystic fibrosis transmembrane conductance regulator (CFTR) corrector. It is available ... "New medicine for cystic fibrosis patients". European Medicines Agency (EMA) (Press release). 26 June 2020. Retrieved 26 June ... "FDA approves new breakthrough therapy for cystic fibrosis". U.S. Food and Drug Administration (FDA) (Press release). October 21 ... is used to treat people with cystic fibrosis who are homozygous for the f508del mutation. This combination was approved for ...
... is essential to the proper folding of cystic fibrosis transmembrane conductance regulator (CFTR). Other examples of co- ... Co-chaperones may also play an important role in misfolding diseases such as cystic fibrosis. An interaction between Hsp90 and ... "Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis". Cell. 127 (4): 803-15. doi:10.1016/j.cell ...
Cystic fibrosis transmembrane conductance regulator (CFTR, also known as ABCC7) is an eukaryotic protein belonging to the ABC-C ... Dysfunction of the CFTR channel causes the life-threatening disease, cystic fibrosis, in which trans-epithelial ion transport ... and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters ( ... Cystic fibrosis transmembrane conductance regulator (IPR009147). Short name: CFTR/ABCC7 Family relationships None. ...
Cystic Fibrosis Transmembrane Conductance Regulator/genetics. *Cystic Fibrosis Transmembrane Conductance Regulator/metabolism* ... The cystic fibrosis transmembrane conductance regulator (CFTR) is the product of the gene mutated in patients with cystic ... Macromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners.. Li C1, Naren AP. ... Cystic Fibrosis/physiopathology. *Cystic Fibrosis Transmembrane Conductance Regulator/chemistry. * ...
The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunctional CFTR in ... Cystic fibrosis (CF) lung disease is characterized by an inflammatory response that can lead to terminal respiratory failure. ... Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation. Guadalupe Ortiz- ... Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation. *Text ...
Very recently, acute downregulation of ENaC by the cystic fibrosis transmembrane … ... conductance in parallel with an enhanced amiloride sensitive Na+ conductance (ENaC) of the respiratory epithelium. ... Cystic fibrosis is characterized by an impaired cyclic adenosine 3,5-monophosphate (cAMP) activated Cl- ... Cystic Fibrosis Transmembrane Conductance Regulator / chemistry * Cystic Fibrosis Transmembrane Conductance Regulator / ...
Cystic fibrosis transmembrane conductance regulator: solution structures of peptides based on the Phe508 region, the most ... Description: PROTEIN (CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR)) protein , Length: 26 No structure alignment ... CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR: SOLUTION STRUCTURES OF PEPTIDES BASED ON THE PHE508 REGION, THE MOST ...
... of all cases of cystic fibrosis. This residue lies in a region of the protein that we have synthesized chemically and shown to ... in the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes approximately 70% ... The cystic fibrosis transmembrane conductance regulator. Effects of the most common cystic fibrosis-causing mutation on the ... in the cystic fibrosis transmembrane conductance regulator (CFTR) protein causes approximately 70% of all cases of cystic ...
Novel action of the chalcone isoliquiritigenin as a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor: ... analysis of T84 cell monolayers indicated that ISLQ blocked mainly the cystic fibrosis transmembrane conductance regulator ( ...
... the ion transport activity of a cystic fibrosis transmembrane conductance regulator (CFTR) and that is linked to a ... Ma et al., "High-affinity Activators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Conductance ... Macromolecular conjugates of cystic fibrosis transmembrane conductance regulator protein inhibitors and uses therefor ... Macromolecular conjugates of cystic fibrosis transmembrane conductance regulator protein inhibitors and uses therefor ...
... cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; CMAC, 7-amino-4-chloromethylcoumarin; ECL, enhanced ... Role of calpain in the regulation of CFTR (cystic fibrosis transmembrane conductance regulator) turnover. Monica Averna, ... The level of the mature native 170 kDa form of CFTR (cystic fibrosis transmembrane conductance regulator) at the plasma ... Role of calpain in the regulation of CFTR (cystic fibrosis transmembrane conductance regulator) turnover ...
"Interactions between Impermeant Blocking Ions in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore ... Dynamic control of cystic fibrosis transmembrane conductance regulator Cl-/HCO 3 - selectivity by external Cl- ... Novel regulation of cystic fibrosis transmembrane conductance regulator (CFTR) channel gating by external chloride ... Heterologous expression systems for study of cystic fibrosis transmembrane conductance regulator. Chang, X.-B.; Kartner, N.; ...
Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal homeostasis ... The olfactory epithelium (OE) of mice deficient in cystic fibrosis transmembrane conductance regulator (CFTR) exhibits ion ... The olfactory epithelium (OE) of mice deficient in cystic fibrosis transmembrane conductance regulator (CFTR) exhibits ion ... Download PDF Novel role of cystic fibrosis transmembrane conductance regulator in maintaining adult mouse olfactory neuronal ...
Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ... Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ... Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ... Stable dimeric assembly of the second membrane-spanning domain of CFTR (cystic fibrosis transmembrane conductance regulator) ...
What is cystic fibrosis transmembrane conductance regulator gene? Meaning of cystic fibrosis transmembrane conductance ... What does cystic fibrosis transmembrane conductance regulator gene mean? ... cystic fibrosis transmembrane conductance regulator gene explanation free. ... Looking for online definition of cystic fibrosis transmembrane conductance regulator gene in the Medical Dictionary? ...
... defective osteoblast maturation with the f508del mutation in cystic fibrosis transmembrane conductance regulator. Frédéric ... defective osteoblast maturation with the f508del mutation in cystic fibrosis transmembrane conductance regulator.. American ... Frédéric Velard, Martial Delion, Carole Le Henaff, Christine Guillaume, Sophie Gangloff, et al.. Cystic fibrosis and bone ...
Whether the cystic fibrosis transmembrane conductance regulator (CFTR) plays a direct role in bone cell function is yet unknown ... Bone loss is an important clinical issue in patients with cystic fibrosis (CF). ... Cystic fibrosis transmembrane conductance regulator (CFTR) regulates the production of osteoprotegerin (OPG) and prostaglandin ... Whether the cystic fibrosis transmembrane conductance regulator (CFTR) plays a direct role in bone cell function is yet unknown ...
Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and ... 246 with nonsense mutations in each CF gene has no detectable cystic fibrosis transmembrane conductance regulator (CFTR) ... Cystic fibrosis (CF) is the most common, lethal inherited disorder in the Caucasian population. We have recently reported two ... W1316X in respiratory epithelial cells of patients with cystic fibrosis Academic Article Overview. MeSH Major * Bronchi ...
The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette superfamily, is a cAMP- ... N2 - The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette superfamily, is a ... AB - The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette superfamily, is a ... abstract = " The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette superfamily, ...
We developed molecular models for the cystic fibrosis transmembrane conductance regulator chloride channel based on the ... Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path ... Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path ... Animals, Anions, Cystic Fibrosis Transmembrane Conductance Regulator, Humans, Ion Transport, Models, Molecular, Molecular ...
"Cystic fibrosis transmembrane conductance regulator and the etiology and pathogenesis of cystic fibrosis". FASEB J. 6 (10): ... The Cystic Fibrosis Transmembrane Conductance Regulator Protein The Human Gene Mutation Database - CFTR Records Cystic Fibrosis ... "Relationships between cystic fibrosis transmembrane conductance regulator, extracellular nucleotides and cystic fibrosis". ... Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is ...
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.. Denning GM1, Anderson MP, ... Cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane Cl- channel regulated by cyclic AMP-dependent ... The most common mutation in cystic fibrosis is deletion of phenylalanine at residue 508 (CFTR delta F508) (ref. 10). Studies on ... Mutations in CFTR cause cystic fibrosis partly through loss of cAMP-regulated Cl- permeability from the plasma membrane of ...
A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype Message Subject (Your Name) has ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ...
Buy The Cystic Fibrosis Transmembrane Conductance Regulator by Kevin L. Kirk, David C. Dawson from Waterstones today! Click and ... The Cystic Fibrosis Transmembrane Conductance Regulator - Molecular Biology Intelligence Unit (Hardback). Kevin L. Kirk (editor ... The Cystic Fibrosis Transmembrane Conductance Regulator addresses a select series of `hot topics that relate to the function ... Given the general interest in CFTR, this collection will appeal to a broad readership with interests in CFTR, cystic fibrosis, ...
The most common cause of cystic fibrosis is deletion of Phe-508 (delta F508) from the cystic fibrosis transmembrane conductance ... The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi ... The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi ... The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi ...
A phenotypic high-throughput screen to identify modulators that improve mutant cystic fibrosis transmembrane conductance ... High-throughput screening Drug Discovery Drug Discovery And Development cystic fibrosis transmembrane conductance regulator ... High-Throughput Screen to Identify Modulators that Improve Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ... High-Throughput Screen to Identify Modulators that Improve Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ...
Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ ... Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ ... We have used in situ hybridization to localize expression of the cystic fibrosis transmembrane conductance regulator (CFTR) ...
X. Wang, J. Matteson, Y. An et al., "COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER ... "Impact of the ΔF508 mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on ... "Multiple membrane-cytoplasmic domain contacts in the cystic fibrosis transmembrane conductance regulator (CFTR) mediate ... Models of Mutations in the Nucleotide Binding Domain 1 of the Cystic Fibrosis Transmembrane Conductance Regulator. Debra J. ...
Mutations of the CFTR gene cause cystic fibrosis (CF), the most common recessive monogenic disease worldwide. These mutations ... Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives Béla Z Schmidt,1 Jérémy ... Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives. *Abstract ...
A phenotypic high-throughput screen to identify modulators that improve mutant cystic fibrosis transmembrane conductance ... regulator (CFTR) activity is described in the SLAS Discovery February 2018 front cover feature article by Giuliano and ... High-Throughput Screen to Identify Modulators that Improve Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ... High-Throughput Screen to Identify Modulators that Improve Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ...
Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have a Non-G551D CF Transmembrane Conductance Regulator (CFTR) ... who have a non-G551D cystic fibrosis transmembrane regulator (CFTR) gating mutation (any one of the following CFTR mutations: ... Fibrosis. Cystic Fibrosis. Pathologic Processes. Pancreatic Diseases. Digestive System Diseases. Lung Diseases. Respiratory ... The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) ...
Cystic fibrosis (CF) is caused by mutations in the CF gene, which encodes CF transmembrane conductance regulator protein (CFTR ... Aspirin and Some Other Nonsteroidal Anti-Inflammatory Drugs Inhibit Cystic Fibrosis Transmembrane Conductance Regulator Protein ... a transmembrane protein that acts as a cAMP-regulated chloride channel. The disease is characterized by inflammation but the ...
... which may be associated with endothelial cell expression of the cystic fibrosis transmembrane conductance regulator (CFTR). ... which may be associated with endothelial cell expression of the cystic fibrosis transmembrane conductance regulator (CFTR). ... BackgroundPerturbation of endothelial function in people with cystic fibrosis (CF) has been reported, ... Perturbation of endothelial function in people with cystic fibrosis (CF) has been reported, ...
Membrane trafficking of the cystic fibrosis gene product, cystic fibrosis transmembrane conductance regulator, tagged with ... The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein is an epithelial cell receptor for the outer core ... Localization of Cystic Fibrosis Transmembrane Conductance Regulator to Lipid Rafts of Epithelial Cells Is Required for ... Cystic fibrosis transmembrane conductance regulator is required for protein kinase A activation of an outwardly rectified anion ...
Pollock, N., Cant, N., Rimington, T., Ford, R. C. Purification of the Cystic Fibrosis Transmembrane Conductance Regulator ... A novel procedure for the efficient purification of the cystic fibrosis transmembrane conductance regulator (CFTR). Biochem J. ... Purification and crystallization of the cystic fibrosis transmembrane conductance regulator (CFTR). J Biol Chem. 279, 39051- ... a novel effective detergent for solubilizing and purifying the cystic fibrosis transmembrane conductance regulator. Anal ...
Deleterious impact of Pseudomonas aeruginosa on cystic fibrosis transmembrane conductance regulator function and rescue in ... Deleterious impact of Pseudomonas aeruginosa on cystic fibrosis transmembrane conductance regulator function and rescue in ... Deleterious impact of Pseudomonas aeruginosa on cystic fibrosis transmembrane conductance regulator function and rescue in ... Deleterious impact of Pseudomonas aeruginosa on cystic fibrosis transmembrane conductance regulator function and rescue in ...
... cystic fibrosis transmembrane conductance regulator) in rat was determined. ...
ATP-binding cassette (ABC), cystic fibrosis transmembrane conductance regulator (CFTR), crystallization, membrane protein, ... and nucleotide-bound forms of the cystic fibrosis transmembrane conductance regulator (CFTR) protein N.H. Awayn N.H. Awayn 1 ... Cystic fibrosis, one of the major human inherited diseases, is caused by defects in the CFTR (cystic fibrosis transmembrane ... and nucleotide-bound forms of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Biochem Soc Trans 26 ...
... cystic fibrosis; K18, keratin 18; CFTR, cystic fibrosis transmembrane conductance regulator; CFPAC, cystic fibrosis pancreatic ... Rescue of ΔF508-CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) by Curcumin: Involvement of the Keratin 18 Network. ... Rescue of ΔF508-CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) by Curcumin: Involvement of the Keratin 18 Network. ... Rescue of ΔF508-CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) by Curcumin: Involvement of the Keratin 18 Network. ...
ABBREVIATIONS: CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator(s); P2YR, P2Y nucleotide receptor ... The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a cAMP-dependent Cl- channel that is defective in CF ... Pharmacological and Signaling Properties of Endogenous P2Y1 Receptors in Cystic Fibrosis Transmembrane Conductance Regulator- ... Pharmacological and Signaling Properties of Endogenous P2Y1 Receptors in Cystic Fibrosis Transmembrane Conductance Regulator- ...
Evidence supporting the occurrence of oxidative stress in Cystic Fibrosis (CF) is well established and the literature suggests ... Characterization of mitochondrial function in cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) ... VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane- ... exchanger regulatory factor isoform 1 overexpression modulates cystic fibrosis transmembrane conductance regulator (CFTR) ...
  • Cystic fibrosis transmembrane conductance regulator (CFTR) play the main role in waterfulux in intestine, and it closely related with bacterial clearance. (tokushima-u.ac.jp)
  • The cystic fibrosis transmembrane conductance regulator (CFTR) epithelial anion channel is a large multi-domain membrane protein which matures inefficiently during biosynthesis. (biomarketx.net)
  • The company said the FDA granted a Breakthrough Therapy Designation for its PTI-428, a cystic fibrosis transmembrane conductance regulator (CFTR) amplifier. (benzinga.com)
  • 1 Genistein (GST), an inhibitor of protein tyrosine kinase (PTK), Na3VO4 (VO4), an inhibitor of phosphotyrosine phosphatase (PTPase), and forskolin (FSK), an activator of the cyclic AMP‐dependent, cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel, were applied to guinea‐pig ventricular myocytes to probe for a possible role of tyrosine phosphorylation in the regulation of cardiac Cl− channels. (semanticscholar.org)
  • In CF many of the adverse changes that result from the defective expression of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene may be preventable or reversible, owing to the fact that the misfolding of the CFTR gene product has been shown to undergo partial or full correction (in the rodent model) when exposed to phytochemicals found in turmeric , cayenne , and soybean . (greenmedinfo.com)
  • Moreover, nutritional deficiencies of seleniun, zinc, riboflavin, vitamin e, etc. in the womb or early in life, may "trigger" the faulty expression or folding patterns of the CFTR gene in Cystic Fibrosis which might otherwise have avoided epigenetic activation. (greenmedinfo.com)
  • Conformationally constrained bithiazoles were previously found to have improved efficacy over nonconstrained bithiazoles for correction of defective cellular processing of the δF508 mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. (elsevier.com)
  • Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis. (expasy.org)
  • Molecular characterization of cystic fibrosis: 16 novel mutations identified by analysis of the whole cystic fibrosis conductance transmembrane regulator (CFTR) coding regions and splice site junctions. (expasy.org)
  • Detection of five novel mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in Pakistani patients with cystic fibrosis: Y569D, Q98X, 296+12(T>C), 1161delC and 621+2(T>C). (expasy.org)
  • Cystic fibrosis is caused by an inherited mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. (medicalxpress.com)
  • Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. (expasy.org)
  • The disease results from mutations in the gene for the cystic fibrosis stransmembrane conductance regulator (CFTR), a cAMP-activated Cl - channel in the apical membrane of most secretory epithelia. (elsevier.com)
  • We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. (elsevier.com)
  • Major historical advances in cystic fibrosis (CF) respiratory clinical care, including mechanical airway clearance and inhaled medications, have aimed to address the consequences of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. (edu.au)
  • They are called cystic fibrosis transmembrane conductance regulator (CFTR) modulators. (nm.org)
  • In CF, a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator ( CFTR ) gene results in dehydration of the airway surface liquid (ASL) layer. (lsu.edu)
  • CF is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. (labmedicineblog.com)
  • Diagnosis is confirmed using genetic testing to look for mutations of the CFTR gene (Cystic Fibrosis Transmembrane conductance Regulator). (vallhebron.com)
  • Cystic fibrosis occurs when mutations in the CFTR gene hamper the function of the Cystic Fibrosis transmembrane conductance regulator. (netherlandsinnovation.nl)
  • The chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR) exists in the apical membrane of exocrine epithelial cells in the body. (asploro.com)
  • In order to define novel cis regulatory elements in the ∼2.7-kb promoter region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, we define its nucleosome occupancy. (ox.ac.uk)
  • The disease is caused by a mutation of the gene that produces the cystic fibrosis transmembrane conductance regulator (Cftr), whose malfunctioning affects multiple organs, especially the lungs. (worldfamousastro.com)
  • Cystic fibrosis TM conductance regulator (CFTR), regulator domain RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120 The following sections contain reference sequences that belong to a specific genome build. (paulbulteel.eu)
  • Abstract VX-770 (Ivacaftor) has been approved for clinical usage in cystic fibrosis patients with several CFTR mutations. (paulbulteel.eu)
  • Changes (mutations) in a gene called the CFTR (cystic fibrosis conductance transmembrane regulator) gene cause CF. The CFTR mutations cause changes in the body's electrolyte transport system. (munsonhealthcare.org)
  • Cystic fibrosis is a hereditary disease that could be caused by single-point mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that normally regulates chloride and bicarbonate transportation. (scienmag.com)
  • CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which results in either no CFTR protein or an abnormal CFTR protein that does not function properly. (algipharma.com)
  • BACKGROUND: Small interfering RNA (siRNA) against alphaENaC (alpha-subunit of the epithelial Na channel) and CFTR (cystic fibrosis transmembrane conductance regulator) was used to explore ENaC and CTFR function in newborn rat lungs. (omeka.net)
  • Genetics Lab Cystic Fibrosis Information source: http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/cftr.shtml Cystic fibrosis is a serious genetic disorder caused by a deletion mutation, ΔF508, of the CFTR (cystic fibrosis transmembrane conductance regulator) gene located on chromosome 7. (studyres.com)
  • Exhaled nitric oxide in stable adult cystic fibrosis patients, during exacerbation and following CFTR-modifying treatment. (covidauthors.org)
  • The clinical-stage biopharmaceutical company released data from its investigation of its ELX-02 candidate treatment showing that it resulted in restored activity for a key cystic fibrosis transmembrane conductance regulator protein. (yahoo.com)
  • Cystic Fibrosis Transmembrane Conductance Regulator-Like Protein in Hydra spp. (sdsu.edu)
  • This is a large gene which codes for a large, transmembrane protein that acts as a chloride channel. (labmedicineblog.com)
  • Other prior research experiences as an undergraduate and medical student included working with Max Cooper (UAB, Immunology), George Philips (Duke, Hematology), Eric Sorshcer (UAB, Cystic Fibrosis), and John Northup (NIH, G-protein Signaling). (uab.edu)
  • Background Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. (paulbulteel.eu)
  • TMEM16A-targeted therapies can be used alone or in conjunction with other CF therapies, namely those that target the cystic fibrosis transmembrane conductance regulator ( CTFR ) gene -the defective gene in CF patients. (cysticfibrosisnewstoday.com)
  • AlgiPharma has received more than USD 37 million in research and development grants from EU's 7th framework program, Horizon 2020, and Eurostars programs, the Norwegian Research Council, Innovate UK, US Army through Congressional Earmark funding, and the Cystic Fibrosis Foundation (CFF). (algipharma.com)
  • Cystic fibrosis (CF) is one of the most common autosomal recessive disorders associated with decreased longevity in the Caucasian population. (elsevier.com)
  • Raising a child with cystic fibrosis can bring up many questions because CF affects many aspects of your child's life. (cff.org)
  • Cystic fibrosis (CF) is an inherited disease that mostly affects the respiratory and digestive systems. (nm.org)
  • Cystic fibrosis is a genetic disorder that affects the lungs, the digestive system and other organs in the body. (vallhebron.com)
  • Cystic fibrosis affects the cells that produce mucus, sweat and digestive enzymes. (vallhebron.com)
  • Cystic fibrosis (CF) is an inherited life-threatening disease that affects many organs. (munsonhealthcare.org)
  • Cystic fibrosis (CF) is a life-threatening disease that affects the lungs and digestive system and impacts about 70,000 people worldwide. (algipharma.com)
  • Eloxx expects to report data from a phase 2 study of ELX-02 in cystic fibrosis patients later in 2019. (yahoo.com)
  • Use of cystic fibrosis transmembrane conductance regulator modulator therapy in patients with cystic fibrosis. (guidelinecentral.com)
  • The news is welcome for patients "who live their daily lives suffering from cystic fibrosis and are waiting to learn if potential new treatments can help them," said Sen Bennet. (pharmatimes.com)
  • Patients with cystic fibrosis have a much higher level of salt in their sweat than normal. (vallhebron.com)
  • There has been an improvement in the quality of life of patients with cystic fibrosis compared to previous decades. (vallhebron.com)
  • Although cystic fibrosis requires daily treatment measures to control it, patients can still go to school and work. (vallhebron.com)
  • Banjar H, Kadan H, Al-Abdaly D, Sheikh M, Al-Kaf S, Ghomraoui R, AIDoss A, Al-Eid M. Demographic Data of Cystic Fibrosis Patients in a Tertiary Care Center in Saudi Arabia. (asploro.com)
  • To present the demographic data of Cystic Fibrosis patients and their families, that involves their social status and education. (asploro.com)
  • A total of 430 confirmed Cystic Fibrosis patients. (asploro.com)
  • Forty-five had a family history of Cystic Fibrosis, and the diagnosis was suggested by family history in 9.5% of patients. (asploro.com)
  • The researcher emphasized a novel aspect of the study: "Instead of animal models, we have used organoids that we developed from the patients' cells, a choice that allowed us to verify the efficacy of the molecular strategy in a context that is very similar to that of the patients with cystic fibrosis. (worldfamousastro.com)
  • The AlgiPharma team recognizes the value in establishing a strong presence in Australia to help bring its lead drug candidate, OligoG, to the market for the treatment of patients suffering with Cystic Fibrosis. (algipharma.com)
  • TMEM16A potentiation has the potential to significantly increase the quality of life for people living with cystic fibrosis , for many of whom existing therapies are not effective," Ford added. (cysticfibrosisnewstoday.com)
  • Cystic fibrosis: diagnosis and management. (guidelinecentral.com)
  • Currently screening for cystic fibrosis is conducted in the first few days of a baby's life, allowing a diagnosis to be made within a month of birth, much earlier than symptoms are likely to develop. (vallhebron.com)
  • AlgiPharma has completed 5 clinical trials with two formulations of its lead drug candidate, OligoG, to treat respiratory symptoms of cystic fibrosis. (algipharma.com)
  • The CF Foundation offers a number of resources for learning about clinical trials and treatments that are being developed to improve the treatment of cystic fibrosis. (cff.org)
  • Roche has acquired Enterprise Therapeutics' s TMEM16A potentiator portfolio, which includes ETD002 , a therapeutic candidate being evaluated in Phase 1 clinical trials for the treatment of cystic fibrosis (CF). (cysticfibrosisnewstoday.com)
  • Cystic Fibrosis Foundation-accredited care centers provide expert care and specialized disease management to people living with cystic fibrosis. (cff.org)
  • The Cystic Fibrosis Foundation is the world's leader in the search for a cure for CF and supports a broad range of research initiatives to tackle the disease from all angles. (cff.org)
  • Characterization of 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator. (expasy.org)
  • Cystic fibrosis (CF) is the most common potentially lethal genetic disease in the Caucasian population. (elsevier.com)
  • Sweat chloride concentrations are measured in people who are suspected of having Cystic Fibrosis (CF). Because CF has classically been considered a disease of childhood, sweat chloride testing is performed almost exclusively in pediatric institutions. (labmedicineblog.com)
  • The fight against cystic fibrosis, a genetic disease for which no cure is currently available, continues, targeting in particular some of the mutations that cause it. (worldfamousastro.com)
  • Cystic fibrosis is also called "the invisible disease" because it has no external indicators, and yet it takes a huge toll on the lives of the people it afflicts, primarily via lung and digestive problems. (worldfamousastro.com)
  • Cystic Fibrosis News Today is strictly a news and information website about the disease. (cysticfibrosisnewstoday.com)
  • People with cystic fibrosis are living longer and more fulfilling lives, thanks in part to specialized CF care and a range of treatment options. (cff.org)
  • The Cystic Fibrosis Unit designs a treatment plan for each patient, which varies over time and according to the evolution of the condition. (vallhebron.com)
  • The approach adopted by the team, led by Anna Cereseto, opens new perspectives in the treatment of cystic fibrosis. (worldfamousastro.com)
  • Within the scope of this new perspective even classical monogenic diseases like Cystic Fibrosis (CF) can be viewed in a new, more promising light. (greenmedinfo.com)
  • The US Food and Drug Administration (FDA)'s first Breakthrough Therapy Designations have been granted to two cystic fibrosis (CF) treatments from Vertex Pharmaceuticals. (pharmatimes.com)
  • Hartman has also received support through a K08 Career Development Award from NCI, American Cancer Society Research Scholar Grant, Cystic Fibrosis Foundation Research Grants, and R01 funding from NIA and NHLBI. (uab.edu)
  • Rice University chemical and biomolecular engineer Xue Sherry Gao, with graduate students Qichen Yuan, left, and Zane Zeng, has won a prestigious National Institutes of Health grant to develop personalized gene editing techniques for cystic fibrosis. (scienmag.com)
  • As part of the Cystic Fibrosis Foundation's mission to help improve the lives of people living with cystic fibrosis, the PSDC initiative taps the CF community to inform key efforts to support the management of daily care. (cff.org)
  • Many people living with cystic fibrosis and their families face complicated issues related to getting the care they need. (cff.org)
  • There are about 6,000 people with cystic fibrosis in Italy, and 200 new cases every year. (worldfamousastro.com)
  • Here we describe a Pro residue in the center of the third transmembrane helix of the cystic fibrosis transmembrane conductance regulator that promotes folding by a distinct mechanism: disfavoring the formation of a misfolded structure. (elsevier.com)
  • It will also allow us to create a library of cystic fibrosis cell lines we can use to study whether small molecule drugs are effective. (scienmag.com)
  • Cystic Fibrosis Foundation pulmonary guidelines. (guidelinecentral.com)
  • The Cystic Fibrosis Foundation provides standard care guidelines based on the latest research, medical evidence, and consultation with experts on best practices. (cff.org)
  • Cystic Fibrosis Foundation Compass makes sure that no one has to do it alone. (cff.org)
  • Activation of background membrane conductance by the tyrosine kinase inhibitor tyrphostin A23 and its inactive analog tyrphostin A1 in guinea pig ventricular myocytes. (semanticscholar.org)
  • Your cystic fibrosis care team includes a group of CF health care professionals who partner with you to provide specialized, comprehensive CF care. (cff.org)
  • If you or your child has just been diagnosed with cystic fibrosis, or your doctor has recommended testing for CF, you may have many questions. (cff.org)
  • HOUSTON - (April 8, 2021) - Chemical and biomolecular engineer Xue Sherry Gao of Rice University's Brown School of Engineering has won National Institutes of Health support for a new strategy to fight cystic fibrosis. (scienmag.com)