An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
Also known as CD104 antigen, this protein is distinguished from other beta integrins by its relatively long cytoplasmic domain (approximately 1000 amino acids vs. approximately 50). Five alternatively spliced isoforms have been described.
This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.
Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.
A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.
Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.
A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)
A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems.
Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.
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.
Established cell cultures that have the potential to propagate indefinitely.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
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.
One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The beta-3 adrenergic receptors are the predominant beta-adrenergic receptor type expressed in white and brown ADIPOCYTES and are involved in modulating ENERGY METABOLISM and THERMOGENESIS.
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.
Adherence of cells to surfaces or to other cells.
Brain waves with frequency between 15-30 Hz seen on EEG during wakefulness and mental activity.
Drugs that selectively bind to and activate beta-adrenergic receptors.
A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC
Proteins prepared by recombinant DNA technology.
Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS.
A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.
Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
The rate dynamics in chemical or physical systems.
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.
AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.
Receptors such as INTEGRIN ALPHAVBETA3 that bind VITRONECTIN with high affinity and play a role in cell migration. They also bind FIBRINOGEN; VON WILLEBRAND FACTOR; osteopontin; and THROMBOSPONDINS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
Nucleocytoplasmic transport molecules that bind to ALPHA KARYOPHERINS in the CYTOSOL and are involved in transport of molecules through the NUCLEAR PORE COMPLEX. Once inside the CELL NUCLEUS beta karyopherins interact with RAN GTP-BINDING PROTEIN and dissociate from alpha karyopherins. Beta karyopherins bound to RAN GTP-BINDING PROTEIN are then re-transported to the cytoplasm where hydrolysis of the GTP of RAN GTP-BINDING PROTEIN causes release of karyopherin beta.
A phosphoinositide phospholipase C subtype that is primarily regulated by its association with HETEROTRIMERIC G-PROTEINS. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of C-terminal extension of 400 residues.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
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.
Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.
A forkhead transcription factor that regulates expression of metabolic GENES and is involved in EMBRYONIC DEVELOPMENT. Mutations in HNF-3beta have been associated with CONGENITAL HYPERINSULINISM.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
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).
An integrin that binds to a variety of plasma and extracellular matrix proteins containing the conserved RGD amino acid sequence and modulates cell adhesion. Integrin alphavbeta3 is highly expressed in OSTEOCLASTS where it may play role in BONE RESORPTION. It is also abundant in vascular smooth muscle and endothelial cells, and in some tumor cells, where it is involved in angiogenesis and cell migration. Although often referred to as the vitronectin receptor there is more than one receptor for vitronectin (RECEPTORS, VITRONECTIN).
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A hepatocyte nuclear factor that is closely related to HEPATOCYTE NUCLEAR FACTOR 1-ALPHA but is only weakly expressed in the LIVER. Mutations in hepatocyte nuclear factor 1-beta are associated with renal CYSTS and MATURITY-ONSET DIABETES MELLITUS type 5.
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 degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
Elements of limited time intervals, contributing to particular results or situations.
The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.
The beta subunit of human CHORIONIC GONADOTROPIN. Its structure is similar to the beta subunit of LUTEINIZING HORMONE, except for the additional 30 amino acids at the carboxy end with the associated carbohydrate residues. HCG-beta is used as a diagnostic marker for early detection of pregnancy, spontaneous abortion (ABORTION, SPONTANEOUS); ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA; or DOWN SYNDROME.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Antibodies produced by a single clone of cells.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
High energy POSITRONS or ELECTRONS ejected from a disintegrating atomic nucleus.
Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
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.
A TGF-beta subtype that was originally identified as a GLIOBLASTOMA-derived factor which inhibits the antigen-dependent growth of both helper and CYTOTOXIC T LYMPHOCYTES. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta2 and TGF-beta2 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
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.
Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Serum proteins with an electrophoretic mobility that falls between ALPHA-GLOBULINS and GAMMA-GLOBULINS.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
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.
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.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Peptides composed of between two and twelve amino acids.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
A TGF-beta subtype that plays role in regulating epithelial-mesenchymal interaction during embryonic development. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta3 and TGF-beta3 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A cell line derived from cultured tumor cells.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
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.
Drugs that bind to and block the activation of ADRENERGIC BETA-3 RECEPTORS.
One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity.
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.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Transport proteins that carry specific substances in the blood or across cell membranes.
A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.
A species of the Beta genus. Cultivars are used as a source of beets (root) or chard (leaves).
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Collagen receptors are cell surface receptors that modulate signal transduction between cells and the EXTRACELLULAR MATRIX. They are found in many cell types and are involved in the maintenance and regulation of cell shape and behavior, including PLATELET ACTIVATION and aggregation, through many different signaling pathways and differences in their affinities for collagen isoforms. Collagen receptors include discoidin domain receptors, INTEGRINS, and glycoprotein VI.
A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Glycoproteins with the electrophoretic mobility of BETA-GLOBULINS, secreted by the placental TROPHOBLASTS into the maternal bloodstream during PREGNANCY. They can be detected 18 days after OVULATION and reach 200 mg/ml at the end of pregnancy. They are associated with fetal well-being.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Thymosin. A family of heat-stable, polypeptide hormones secreted by the thymus gland. Their biological activities include lymphocytopoiesis, restoration of immunological competence and enhancement of expression of T-cell characteristics and function. They have therapeutic potential in patients having primary or secondary immunodeficiency diseases, cancer or diseases related to aging.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
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.
DNA sequences encoding the beta chain of the T-cell receptor. The genomic organization of the TcR beta genes is essentially the same in all species and is similar to the organization of Ig genes.
The regulatory subunits of large-conductance calcium-activated potassium channels.
Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN GAMMA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.
The characteristic 3-dimensional shape of a carbohydrate.
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.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
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.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
An adrenergic beta-2 agonist that is used as a bronchodilator and tocolytic.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A calcium-binding protein that is 92 AA long, contains 2 EF-hand domains, and is concentrated mainly in GLIAL CELLS. Elevation of S100B levels in brain tissue correlates with a role in neurological disorders.
A blood plasma glycoprotein that mediates cell adhesion and interacts with proteins of the complement, coagulation, and fibrinolytic cascade. (From Segen, Dictionary of Modern Medicine, 1992)
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
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).)
Enzymes that catalyze the transfer of N-acetylglucosamine from a nucleoside diphosphate N-acetylglucosamine to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
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.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.
A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia.
Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.
Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.
Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).
The sum of the weight of all the atoms in a molecule.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
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.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.
Enzymes that catalyze the transfer of galactose from a nucleoside diphosphate galactose to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.
The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
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 study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains.
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).
Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.
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.
Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A member of the tumor necrosis factor receptor superfamily. It has specificity for LYMPHOTOXIN ALPHA1, BETA2 HETEROTRIMER and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 14. The receptor plays a role in regulating lymphoid ORGANOGENESIS and the differentiation of certain subsets of NATURAL KILLER T-CELLS. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.

Physiological role of the N-terminal processed P4501A1 targeted to mitochondria in erythromycin metabolism and reversal of erythromycin-mediated inhibition of mitochondrial protein synthesis. (1/216)

Recently, we showed that the major species of beta-naphthoflavone-inducible rat liver mitochondrial P450MT2 consists of N-terminal truncated microsomal P4501A1 (+33/1A1) and that the truncated enzyme exhibits different substrate specificity as compared with intact P4501A1. The results of the present study show that P450MT2 targeted to COS cell mitochondria by transient transfection of P4501A1 cDNA is localized inside the mitochondrial inner membrane in a membrane-extrinsic orientation. Co-expression with wild type P4501A1 and adrenodoxin (Adx) cDNAs resulted in 5-7-fold higher erythromycin N-demethylation (ERND) in the mitochondrial fraction but minimal changes in the microsomal fraction of transfected cells. Erythromycin, a potent inhibitor of bacterial and mitochondrial protein synthesis, caused 8-12-fold higher accumulation of CYP1A1 mRNA, preferential accumulation of P450MT2, and 5-6-fold higher ERND activity in the mitochondrial compartment of rat C6 glioma cells. Consistent with the increased mitochondrial ERND activity, co-expression with P4501A1 and Adx in COS cells rendered complete protection against erythromycin-mediated mitochondrial translation inhibition. Mutations that specifically affect the mitochondrial targeting of P4501A1 also abolished protection against mitochondrial translation inhibition. These results for the first time suggest a physiological function for the xenobiotic inducible cytochrome P4501A1 against drug-mediated mitochondrial toxicity.  (+info)

7-ethoxycoumarin deethylation activity in perfused isolated rat brain. (2/216)

7-ethoxycoumarin (7-EC) deethylation activity was measured in the perfused rat brain in situ. Infusion of 7-EC into a brain through an internal carotid artery resulted in the formation of 7-hydroxycoumarin (7-HC) and its conjugates in the effluent perfusate collected from the superior vena cava. The rate of formation of products was 200 nmol/h/g when 130 microM 7-EC was infused. This value was much higher (more than 100 times) than that determined from the brain microsomal activity ( approximately 1 nmol/h/g), indicating that the activity determined with microsomes was an underestimate. This value was comparable to the activity in the perfused liver (30-50%), suggesting that drug metabolizing enzymes can play important roles within the brain. Pretreatment of rats with P-450 inducers such as phenobarbital and beta-naphthoflavone increased the deethylation activity in the perfused brain, as in the perfused liver. We conclude that the perfused brain is suitable for evaluating drug metabolizing activities under physiological conditions.  (+info)

Effect of cryopreservation on cytochrome P-450 enzyme induction in cultured rat hepatocytes. (3/216)

In the present study, we evaluated the inducibility of cytochrome P-450 (CYP) CYP1A, CYP2B, CYP3A, and CYP4A by beta-naphthoflavone, phenobarbital, dexamethasone, and clofibric acid, respectively, in primary hepatocyte cultures prepared from both fresh and cryopreserved rat hepatocytes. Rat hepatocytes were successfully thawed and cultured after cryopreservation in liquid nitrogen for up to 1 month. Percentage of total recovery, viable cell recovery, and final viability of the cells were 68%, 72%, and 85%, respectively. Regardless of whether they were cryopreserved or not, cultured hepatocytes exhibited near-normal morphology. Treatment of cryopreserved hepatocytes with beta-naphthoflavone caused an 8-fold increase in 7-ethoxyresorufin O-dealkylase (CYP1A1/2) activity, with an EC50 of 1.5 microM; treatment with phenobarbital caused a 26-fold increase in 7-pentoxyresorufin O-dealkylase (CYP2B1/2) activity, with an EC50 of 10 microM; treatment with dexamethasone caused a 10-fold increase in testosterone 6beta-hydroxylase (CYP3A1/2) activity, with an EC50 of 1.3 microM, whereas treatment with clofibric acid caused a 3-fold increase in lauric acid 12-hydroxylase (CYP4A1-3) activity, with an EC50 of 170 microM. The induction of CYP1A, CYP2B, CYP3A, and CYP4A enzymes by these inducers was confirmed by Western immunoblotting. The patterns of P-450 induction in cryopreserved rat hepatocytes, in terms of concentration response, reproducibility, magnitude, and specificity of response, were similar to those observed in freshly isolated hepatocytes. Additionally, the magnitude and specificity of induction was similar to that observed in vivo in rats. In conclusion, under the conditions examined, cryopreserved rat hepatocytes appear to be a suitable in vitro system for evaluating xenobiotics as inducers of P-450 enzymes.  (+info)

Kinetics of drug metabolism in rat liver slices: IV. Comparison of ethoxycoumarin clearance by liver slices, isolated hepatocytes, and hepatic microsomes from rats pretreated with known modifiers of cytochrome P-450 activity. (4/216)

To evaluate the theory that within precision-cut liver slices intercellular transport occurs in parallel with cellular metabolism and to illustrate the constraints this places on clearance predictions, the kinetics of ethoxycoumarin O-deethylation have been determined under varying conditions of hepatic cytochrome P-450 activity. Liver slices, isolated hepatocytes, and microsomes were obtained from rats treated with the inducers phenobarbital (PB) and beta-naphthoflavone (betaNF) and the inhibitor aminobenzotriazole (ABT). In hepatocytes and microsomes, a two-site kinetic model with a high-affinity, low-capacity site and an unsaturated low-affinity, high-capacity site described the hydroxycoumarin formation data. There were marked increases in Vmax (2- to 5-fold and 50- to 70-fold for PB and betaNF, respectively) in both systems and in CLint (3- and 9-fold for PB and betaNF, respectively) in hepatocytes and substantial decreases in both parameters (3-8 and 12-23% of control, respectively) in ABT hepatocytes and microsomes. A qualitatively similar response was evident in slices obtained from livers of rats treated with phenobarbital and ABT, but although slices from betaNF livers produced high metabolic rates (comparable to slices obtained from livers of rats treated with phenobarbital), these showed a linear increase with substrate concentration without indication of a high-affinity site. The intrinsic clearance parameters were scaled to full liver capacity using hepatocellularities and microsomal recovery indices to allow direct comparison of these responses. The slice system consistently underestimated the effects of the modifiers. When compared with hepatocytes, estimates of 30, 15, and 1% for ABT, PB, and betaNF, respectively, were observed and the degree of underestimation was dependent on the magnitude of intrinsic clearance and was consistent with the above theory.  (+info)

In vitro sulfoxidation of aldicarb by hepatic microsomes of channel catfish, Ictalurus punctatus. (5/216)

The carbamate pesticide, aldicarb, demonstrates significant acute toxicity in mammals, birds, and fish, and is readily biotransformed by most organisms studied. Metabolic products of aldicarb include the more toxic sulfoxide and the less toxic sulfone as two of the major products. Both the cytochrome P450 (CYP) and the flavin monooxygenase systems (FMO) are involved in this process. This study examined the capacities of liver microsomes of male channel catfish (Ictalurus punctatus), which lack FMO, to biotransform aldicarb in vitro. In addition, the acetylcholinesterase inhibitory potencies of aldicarb and its sulfoxide and sulfone derivatives were determined. For metabolism studies, incubations of [14C]-aldicarb (0.1mM) were carried out for up to 15-90 min using 1.0 mg/mL of hepatic microsomal protein. Total NADPH- dependent biotransformation was low (< 3.0% conversion to polar metabolites), and was inhibited by carbon monoxide. The only metabolite detected was aldicarb sulfoxide (Kmapp = 53.8 +/- 25.3 microM; Vmaxapp = 0.040 +/- 0.007 nmol/min/mg). Treatment of fish with the CYP modulators beta-naphthoflavone (BNF, 50 mg/kg) and ethanol (EtOH, 1.0% aqueous) had no effect on sulfoxide production. No correlation existed between CYP isoform expression (determined by western blot) and aldicarb sulfoxidation rates, suggesting the involvement of an unmeasured CYP isoform or involvement of several isoforms with low specificity. This study indicates that a low rate of bioactivation of aldicarb to aldicarb sulfoxide may be responsible for the resistance of channel catfish to aldicarb toxicity relative to that of other piscine species.  (+info)

Alternatives in the induction and preparation of phenobarbital/naphthoflavone-induced S9 and their activation profiles. (6/216)

With the aim of optimizing the efficiency of S9 fractions used in in vitro mutagenicity assays, different schemes for the induction of liver enzymes in rats were tried and the amount of S9 fraction required was assessed. The activity of 2-anthramine (2AA), 2-acetylaminofluorene (2AAF), 3-methylcholanthrene (3MTCL) and benzo[a]pyrene in bacterial mutagenicity tests was compared with the enzymatic activity in S9 fractions obtained from rats treated with either phenobarbital (NaPB), beta-naphthoflavone (betaNF) or combinations of both. Three pool systems prepared with different amounts of NaPB-induced S9 and betaNF-induced S9 were also analyzed for their activation capacities. Profiles of standard plate incorporation assays with Salmonella typhimurium TA98 increased with the amount of S9 fraction added for all drugs tested, except for 2AA, which showed a maximun of activity at low protein concentrations. According to these profiles, an optimal S9 protein content of 700-1000 microg/plate was estimated. For 2AAF and 3MTCL an S9 fraction obtained following a simultaneous treatment with NaPB (i.p.) and betaNF (oral gavage) (NaPB + betaNF) yielded the greatest response. This preparation was the only one which produced positive activation with 3MTCL as test drug. With the other test drugs all the S9 fractions were very active, including the NAPB + betaNF-induced S9. Both Phase I and Phase II cytochrome P450 enzymatic activities were enhanced in this S9 fraction. These results suggest that the simultaneous treatment (NaPB + betaNF) would be an adequate inducer for in vitro activation when used at 700-1000 microg protein/plate.  (+info)

An expressional system of human cytochrome P-450 CYP1A1 gene transcription. (7/216)

AIM: To explore an expressional system of human cytochrome P-450 CYP1A1 (CYP1A1) gene transcription. METHODS: The plasmid pMC 6.3 K containing human CYP1A1 promoter was transiently transfected into Hep G2 cells. The expression of chloramphenical acetyltransferase (CAT) reporter gene was detected by ELISA. RESULTS: Both the CAT expression and CYP1A1 activity increased with the concentrations of beta-naphthoflavone from 2.5 to 10 mumol.L-1. At 10 mumol.L-1 of beta-naphthoflavone, the levels of CAT and CYP1A1 were 94-fold and 2.8-fold those of the corresponding control, respectively. Using this method, the study of 8 glucosinolates with various side chains on the induction of CYP1A1 gene transcription showed that none of the parent glucosinolates increased CAT expression, whereas the breakdown products of indol-3-yl-methyl glucosinolate (glucobrassicin), rather than indole-3-carbinol, increased the CAT expression. CONCLUSION: The CYP1A1 gene transcriptional system was more reliable and sensitive.  (+info)

Cigarette smoke induces direct DNA damage in the human B-lymphoid cell line Raji. (8/216)

Human lymphoid cells (Raji) were exposed to water-soluble compounds from cigarette smoke (CS) generated in a smoking machine. DNA damage, as detected by alkaline single-cell microelectrophoresis (COMET assay), was induced in a time- and concentration-dependent manner in the cells. Most of the rapidly induced DNA damage was attributable to direct-acting compounds since cytochrome P450-related metabolic activities (ethoxy- and pentoxyresorufin-O-deethylases and coumarin-7-hydroxylase) were absent or very low. In addition, induction of DNA damage could be inhibited only slightly by beta-naphthoflavone and coumarin. Vitamin C enhanced DNA damage in Raji cells probably by redox cycling of catechol and hydroquinone present in CS implicating reactive oxygen intermediates as another source of DNA damage. N-acetylcysteine, a radical scavenger and glutathione precursor, reduced DNA damage in Raji cells when exposure to CS was followed by 2 h post-incubation in culture medium. Unrepaired DNA damage caused by CS persisted longer than gamma-irradiation-induced DNA damage. Among the CS constituents, acrolein, but not formaldehyde and acetaldehyde, induced DNA damage although less intensely than CS itself. At 50 and 100 microM concentrations, acrolein also inhibited repair of gamma- irradiation-induced DNA damage in the COMET assay. Inhibition of DNA synthesis by acrolein at 50 microM was demonstrated by an immunochemical assay for bromo-deoxyuridine incorporation; however, inhibition of a representative repair enzyme, 8-oxoguanosine hydrolase, by either CS or acrolein was not observed. The present results further confirm the presence of direct-acting genotoxic components and inhibitors of DNA repair in the gas phase of tobacco smoke, that may contribute to DNA damage and smoking-associated cancers of the upper aerodigestive tract.  (+info)

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Human antioxidant-response element (hARE) containing two copies of the AP1/AP1-like elements arranged as inverse repeat is known to mediate basal and beta-naphthoflavone-induced transcription of the type 1 NAD(P)H:quinone oxidoreductase (NQO1) gene. Band-shift assays revealed that beta-naphthoflavon …
Beta-naphthoflavone (BNF, DB06732) is an agonist of aryl hydrocarbon receptor (AhR) and a putative chemotherapeutic agent that offers antitumor activity against mammary carcinomas (4C6); nevertheless, its system of actions continues to be uncertain. of advancement, defenses, circadian tempo and tumor biology (7,9,10). The part of AhR in breasts tumor biology offers been thoroughly looked into, and remarkably raising proof shows that the best response of breasts tumor to AhR is definitely reliant upon estrogen receptor (Emergency room) position, ligand existence and cell type (11C13). Deregulation of Emergency room expression is buy TAPI-0 definitely important in the development of breasts tumor, and estrogen-mediated ER alpha dog (ER) activation promotes breasts tumor growth (14). Under particular conditions, agonist-activated AhR requests Emergency room protein ubiquitination and degradation, and upregulation of enzymes that metabolize estrogen, which inhibits estrogen-induced ER-positive ...
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We have analyzed the possible role of the aryl-hydrocarbon receptor (AHR) in the aging process of mice using a homozygous null mouse (Ahr-/-) line as a model. We studied 52 male and female Ahr-/- mice aged from 6-13 months. Forty-six percent died or were ill by 13 months of age. Ahr-/- mice developed age-related lesions in several organs, some of which were apparent after only 9 months of age. Cardiovascular alterations included cardiomyopathy (100%) with hypertrophy and focal fibrosis. Vascular hypertrophy and mild fibrosis were found in the portal areas of the liver (81%), and vascular hypertrophy and mineralization were common in the uterus (70%). Gastric hyperplasia that progressed with age into polyps was evident in the pylorus of 71% of the mice over 9 months of age. Ahr-/- mice had T-cell deficiency in their spleens but not in other lymphoid organs. The immune system deficiency described previously could be the origin for the rectal prolapse found in 48% of the null mice, associated
a Highest concentrations in test (30-50 mM) are 6-10 fold above current guideline recommendations for non-toxic chemicals. In addition, based on cytotoxicity data in other tests, significant cytotoxicity above 50% would have occurred b Phenobarbital and beta-Naphthoflavone Based on other findings of that study, the authors conclude that this effect is due to clastogenic effects rather than gene mutations. EMA has been tested in CHO cells in the presence and absence of metabolic activation (NTP, 2002). The test concentrations are up to the limit of cytotoxicity, but above the current guideline recommendation (5 mg/ml or 10 mM, whichever is the lowest). Apart from the high concentrations the study protocol is comparable to current guideline recommendations with acceptable restrictions. Although not necessary from a technical perspective, but in order to put the results into perspective in the category, two tests from the adjacent members of the category of lower alkyl (C1-C8) methacrylates, methyl ...
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Licha ya vijana wengi kuhitimu wakiwa na elimu nzuri, bado ukosefu wa ajira umekuwa kikwako kikubwa kwao linapokuja suala la kujiimarisha kimaisha na kujenga mustakabali wao.
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There is an increased risk of bleeding when enoxaparin is administered to patients with low body weight. Refer to the BNF or the Shared Care Guideline for dosage adjustments required ...
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We have developed an approach to classify toxicants based upon their influence on profiles of mRNA transcripts. Changes in liver gene expression were examined after exposure of mice to 24 model treatments that fall into five well-studied toxicological categories: peroxisome proliferators, aryl hydrocarbon receptor agonists, noncoplanar polychlorinated biphenyls, inflammatory agents, and hypoxia-inducing agents. Analysis of 1200 transcripts using both a correlation-based approach and a probabilistic approach resulted in a classification accuracy of between 50 and 70%. However, with the use of a forward parameter selection scheme, a diagnostic set of 12 transcripts was identified that provided an estimated 100% predictive accuracy based on leave-one-out cross-validation. Expansion of this approach to additional chemicals of regulatory concern could serve as an important screening step in a new era of toxicological testing.. ...
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mech …
Amino acid analyses and peptide mapping were performed for the four main haemoglobins from the armoured catfish Pterygoplichthys pardalis; component I, which is functionally distinct from the others, is structurally unique, whereas components II, III and IV, functionally indistinguishable, are closely related in structure. Compositional difference indices are calculated for the four components and for the two major haemoglobins from the trout Salmo irideus, and the results are discussed in terms of structural relationships and evolutionary history of fish haemoglobins. ...
Synonyms: AH receptor-interacting protein, AIP, Aryl-hydrocarbon receptor-interacting protein, HBV X-associated protein 2, XAP-2, Immunophilin homolog ARA9, XAP2, ARA9, FKBP16, FKBP37, SMTPHN.. ...
Ceftriaxone has undergone substantial changes which are live in digital versions and will appear in print in BNF for Children 2016-2017 and BNF 72. These changes reflect the updated Summary of Product Characteristics (SPC) for Rocephin® and also advice and feedback from expert opinion and the BNF formulary committees. Indication and dose Indications and doses […]
POTASSIUM PERMANGANATE Prescribing Notes: Available as 0.1% solution, which should be diluted 1 in 10, and as Permitabs®, where 1 tablet dissolved in 4 litres of water provides a 0.01% solution. See BNF and product literature for further information.. BNF Link: ...
Anita C. Rudy, Paula M. Knight, D. Craig Brater and Stephen D. Hall. Stereoselective metabolism of ibuprofen in humans: Administration of R-, S- and racemic ibuprofen JPET 259: 1133-1139, 1991.. The Editor and Publisher regret the errors which appear in two equations printed on page 1135. The corrected equations are: [SEE THE EQUATIONS IN SOURCE PDF].. ...
Moja ya nyumba za walimu katika shule ya msingi Ipyana wilayani Kyela mkoani MbeyaHali ya nyumba za walimu katika shule hiyo ni mbaya kama inavyoonekana...
Several xenobiotics caused hepatic porphyrin accumulation through mechanism-based inactivation of cytochrome P450(P450) and heme alkylation. Loss of iron from the alkylated heme results in formation of an N-alkylporphyrin, which is a potent inhibitor of ferrochelatase. N-Vinylprotoporphyrin IX (N-vinylPP) was identified in chick embryo liver after in ovo administration of 3-[(arylthio)ethyl]sydnone (TTMS). Pretreatment of chick embryos with beta-naphthoflavone, which causes a 90-fold increase in P450 1A levels, did not increase the formation of N-vinylPP after TTMS administration, showing that the heme moiety of P450 1A does not contribute to the formation of N-vinylPP. Increased amounts of N-vinylPP were isolated from dexamethasone-, phenobarbital-, and glutethimide-pretreated chick embryos, and it is possible that P450 2H and/or a P450 3A-like isozyme contributes to the formation of N-vinylPP. The ring B-substituted (NB) regioisomer of N-vinylPP constituted the lowest percentage of the total ...
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Following reports of heart failure, caution is advised when prescribing itraconazole to patients at high risk of heart failure (BNF ...
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Hatua nyingine ni kutenga shule mbili maalum za michezo kwa kila Mkoa pamoja na kuhamasisha wadau kuanzisha shule za aina hiyo, kutoa ushauri elekezi kwa Vyama vya Michezo wakati wa maandalizi ya timu za Taifa zinazoshiriki kwenye michezo ya Kimataifa ikiwemo Olimpiki, Michezo ya Afrika na Michezo ya Jumuiya ya Madola, kuendesha na kuratibu mashindano ya michezo kwa ajili ya wanafunzi wa Shule za Msingi (UMITASHUMTA) na michezo ya Shule za Sekondari (UMISSETA) kwa kushirikiana na Wizara nyingine. ...
Mens Health Network. (n.d.). A vision for wellness and health equity for American Indian and Alaskan Native boys. Retrieved from: ...
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The National Institute of Standards and Technology (NIST) uses its best efforts to deliver a high quality copy of the Database and to verify that the data contained therein have been selected on the basis of sound scientific judgment. However, NIST makes no warranties to that effect, and NIST shall not be liable for any damage that may result from errors or omissions in the Database ...
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The cure can, often, be as bad as the problem. My adrenal glands have failed, to compensate for which I have to take hydrocortisone three times a day. There is not, Im told, and the BNF seems to bear this out, an enteric-coated version of hydrocortisone available (that would keep it from dissolving in my…
TY - JOUR. T1 - Stereoselective metabolism of the environmental mammary carcinogen 6-nitrochrysene to trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene by aroclor 1254-treated rat liver microsomes and their comparative mutation profiles in a lacI mammary epithelial cell line. AU - Sun, Yuan Wan. AU - Guttenplan, Joseph B.. AU - Khmelnitsky, Michael. AU - Krzeminski, Jacek. AU - Boyiri, Telih. AU - Amin, Shantu. AU - El-Bayoumy, Karam. PY - 2009/12/21. Y1 - 2009/12/21. N2 - The environmental pollutant 6-nitrochrysene (6-NC) is a powerful mammary carcinogen and mutagen in rats. Our previous studies have shown that 6-NC is metabolized to trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene (1,2-DHD-6-NC) in rats and in several in vitro systems, including human breast tissue, and the latter is the proximate carcinogenic form in the rat mammary gland. Because optically active enantiomers of numerous polynuclear aromatic hydrocarbon (PAH) metabolites including chrysene have different biological activities, ...
The National Institute of Standards and Technology (NIST) uses its best efforts to deliver a high quality copy of the Database and to verify that the data contained therein have been selected on the basis of sound scientific judgment. However, NIST makes no warranties to that effect, and NIST shall not be liable for any damage that may result from errors or omissions in the Database ...
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The problem here is that if pharmacies receive prescriptions for 60g of the ointment, once its gone, they will be able to properly supply the 120g and be paid for it...but the clinical indication for this product is clear - it shouldnt be used in a casual manner. Indeed the BNF states apply once a day to a maximum of 30% of the body surface for 4 weeks (max of 15g daily); If necessary treatment may be continued beyond the 4 weeks or repeated on the advice of a specialist ...
PLATEARIUS, « Livre des symples medichinos, autrement dit Arboriste, continué selon le A, B, C. » Source: Bibliothèque nationale de France, …. ...
Aug. libri 1-9 de civitate Dei. Source: Bibliothèque nationale de France, Département des manuscrits, Latin 12214, fol. 203r.. ...
Jeshi la Polisi nchini Tanzania limekanusha madai ya ukiukaji haki za binadamu pamoja na mauaji dhidi ya wakazi wa eneo la Nyamongo linalozunguka mgodi wa machimbo ya dhahabu wa North Mara ulioko Wilayani Tarime mkoani Mara.. Katika Ripoti iliyotolewa hivi karibuni kwenye Bunge la Uingereza na Wanaharakati wa masuala ya madini, polisi kwa kushirikiana na kampuni ya African Barrick inayomiliki mgodi wa North Mara walishutumiwa kwa vitendo vya mauaji na ukatili dhidi ya wananchi waishio jirani na mgodi huo.. Erick David Nampesya alitembelea eneo la Nyamongo kwenye mgodi huo.. ...
Serikali ya China imeitolea wito Marekani kuchukua hatua kwa uangalifu juu ya suala la Taiwan ili kuepuka uhasama katika uhusiano kati ya nchi hizi mbili na mdororo wa usalama katika eneo la Taiwan.
Haugen DA, Coon MJ (1976). "Properties of electrophoretically homogeneous phenobarbital-inducible and beta-naphthoflavone- ... beta". Arch. Biochem. Biophys. 267 (1): 31-7. doi:10.1016/0003-9861(88)90004-5. PMID 3264134. Theoharides AD, Kupfer D (1981 ...
... beta-naphthoflavone MeSH D03.438.150.266.450.190 - biflavonoids MeSH D03.438.150.266.450.206 - catechin MeSH D03.438.150.266. ... beta-naphthoflavone MeSH D03.830.219.266.450.190 - biflavonoids MeSH D03.830.219.266.450.206 - catechin MeSH D03.830.219.266. ... beta-tocopherol MeSH D03.830.219.909.750.500 - gamma-tocopherol MeSH D03.830.219.909.875 - tocotrienols The list continues at ... beta-tocopherol MeSH D03.438.150.909.750.500 - gamma-tocopherol MeSH D03.438.150.909.875 - tocotrienols MeSH D03.438.174.138 - ...
The molecular formula C19H12O2 may refer to: alpha-Naphthoflavone (7,8-benzoflavone) beta-Naphthoflavone (5,6-benzoflavone) ...
... may refer to: alpha-Naphthoflavone (7,8-benzoflavone) beta-Naphthoflavone (5,6-benzoflavone) This set index page ...
... β-Naphthoflavone is a putative chemopreventive agent. alpha-Naphthoflavone Aryl hydrocarbon receptor Chlouchi A, Girard C, ... β-Naphthoflavone, also known as 5,6-benzoflavone, is a potent agonist of the aryl hydrocarbon receptor and as such is an ...
... has been shown to cause abnormal testicular development in young chickens. beta-Naphthoflavone C19H12O2 ... alpha-Naphthoflavone, also known as 7,8-benzoflavone and 2-phenyl-benzo(h)chromen-4-one, is a synthetic flavone derivative. It ... alpha-Naphthoflavone is a potent inhibitor of the enzyme aromatase, the enzyme that converts testosterone to estrogen. ... Trefil, P.; Micakova, A.; Stiborova, M.; Poplstein, M.; Brillard, J.P.; Hodek, P. (2004). "Effects of alpha-naphthoflavone on ...
... beta-naphthoflavone)) ...
... beta-naphthoflavone)) ...
... beta-naphthoflavone)) ...
Haugen, D.A. and Coon, M.J. (1976). "Properties of electrophoretically homogeneous phenobarbital-inducible and β-naphthoflavone ... beta". Arch. Biochem. Biophys. 267: 31-37. PMID 3264134. ...
... β-Naphthoflavone is a putative chemopreventive agent. alpha-Naphthoflavone Aryl hydrocarbon receptor Chlouchi A, Girard C, ... β-Naphthoflavone, also known as 5,6-benzoflavone, is a potent agonist of the aryl hydrocarbon receptor and as such is an ...
Hodek E, Krizkova I, Frei V, Singh A, Arlt O, Stiborova A, Impact of beta-naphthoflavone on genotoxicity of food-derived ...
The effects of phenobarbital and beta-naphthoflavone on the elimination kinetics and metabolite pattern of caffeine in the ... The effects of phenobarbital and beta-naphthoflavone on the elimination kinetics and metabolite pattern of caffeine in the ... The effects of phenobarbital and beta-naphthoflavone on the elimination kinetics and metabolite pattern of caffeine in the ... The effects of phenobarbital and beta-naphthoflavone on the elimination kinetics and metabolite pattern of caffeine in the ...
... beta-naphthoflavone (BNF) and 3- methylcholantheren.. Methods: The fish were treated by i.p. injections of beta-naphthoflavone ... Effects of Beta-Naphthoflavone and 3-Methylcholantheren on Biochemical Markers in Sturgeon Fish, Huso huso ... karimzadeh K. Effects of Beta-Naphthoflavone and 3-Methylcholantheren on Biochemical Markers in Sturgeon Fish, Huso huso. IJT. ... Results: Beta-naphthoflovone and 3-methylcholantheren treated-fish developed 15-32 fold increase in Ethoxyresorufin-O- ...
... containing two copies of the AP1/AP1-like elements arranged as inverse repeat is known to mediate basal and beta-naphthoflavone ... beta-naphthoflavone induction of the CAT gene expression in Hepa-1 cells was found insensitive to inhibitors of protein kinase ... Interestingly, the increase in binding of Jun and Fos proteins to the hARE was more prominent with beta-naphthoflavone-treated ... Band-shift assays revealed that beta-naphthoflavone increased binding of nuclear proteins at the hARE. Super shift assays ...
Both class 1 and class 2 mRNAs were elevated in liver by 3-methylcholanthrene, benzo[a]pyrene, beta-naphthoflavone, and ... Exposure to certain chemicals, such as 3-methylcholanthrene, benzo[a]pyrene, beta-naphthoflavone, and oltipraz elevates UGT1A6 ...
Impact of beta-naphthoflavone on genotoxicity of food-derived carcinogens.. Hodek P, Krizkova J, Frei E, Singh R, Arlt V, ... Hodek P, Krizkova J, Frei E, Singh R, Arlt V, Stiborova M. Impact of beta-naphthoflavone on genotoxicity of food-derived ...
DB06732, beta-Naphthoflavone. DB12328, Cantharidin. DB08995, Diosmin. DB07715, Emodin. DB12116, Epigallocatechin gallate. ... DB06732, beta-Naphthoflavone. DB12328, Cantharidin. DB08995, Diosmin. DB07715, Emodin. DB12116, Epigallocatechin gallate. ... Legend: HelixTurnBeta strandPDB Structure known for this area. Show more detailsHide details. Feature key. Position(s). ... Beta strandi. 122 - 124. Combined sources. Manual assertion inferred from combination of experimental and computational ...
alpha-Naphthoflavone has been shown to cause abnormal testicular development in young chickens. beta-Naphthoflavone C19H12O2 ... alpha-Naphthoflavone, also known as 7,8-benzoflavone and 2-phenyl-benzo(h)chromen-4-one, is a synthetic flavone derivative. It ... alpha-Naphthoflavone is a potent inhibitor of the enzyme aromatase, the enzyme that converts testosterone to estrogen. ... Trefil, P.; Micakova, A.; Stiborova, M.; Poplstein, M.; Brillard, J.P.; Hodek, P. (2004). "Effects of alpha-naphthoflavone on ...
beta-Naphthoflavone. experimental. unknown. Details. DB07776. Flavone. approved, experimental. unknown. Details. DB01645. ...
beta-Naphthoflavone. experimental. unknown. inducer. Details. DB00338. Omeprazole. approved, investigational, vet_approved. ... Interferon beta-1b. approved. unknown. inhibitor. Details. DB00060. Interferon beta-1a. approved, investigational. unknown. ... Human interferon beta. approved, investigational. unknown. downregulator. Details. DB01306. Insulin aspart. approved. unknown. ... alpha-Naphthoflavone. experimental. unknown. Details. DB02709. Resveratrol. investigational. unknown. substrateinhibitor. ...
beta-naphthoflavone decreases expression. EXP. 6480464. beta-Naphthoflavone results in decreased expression of NAT8F2 mRNA. CTD ... beta-naphthoflavone multiple interactions. EXP. 6480464. AHR protein affects the reaction [beta-Naphthoflavone results in ...
beta-naphthoflavone multiple interactions. ISO. RGD:1624005. 6480464. [andrographolide co-treated with beta-Naphthoflavone] ... andrographolide co-treated with beta-Naphthoflavone] results in increased expression of EID3 mRNA. CTD. PMID:19737545. ...
a Phenobarbital and beta-Naphthoflavone b Based on other findings of that study, the authors conclude that this effect is due ... b Phenobarbital and beta-Naphthoflavone Based on other findings of that study, the authors conclude that this effect is due to ...
By 3-methylcholanthrene (3MC) and beta-naphthoflavone (BNF).. Gene expression databases. Bgee dataBase for Gene Expression ...
Phenobarbital beta-naphthoflavone induced rat liver S9. Test concentrations with justification for top dose:. 33, 100, 333, ...
Toxicology · beta naphthoflavone · cytochrome p450 · glutathione · paracetamol · paracetamol derivative · phenobarbital · ... Chemicals/CAS: Acetaminophen, 103-90-2; Benzoquinones; beta-Naphthoflavone, 6051-87-2; Cytochrome P-450 Enzyme System, 9035-51- ... beta-Naphthoflavone · Cytochrome P-450 Enzyme System · Gas Chromatography-Mass Spectrometry · Glutathione · Imines · Kinetics ... The GSSG-formation was increased in all cases upon pretreatment of rats by β-naphthoflavone (βNF) and was generally decreased ...
S9 from induced phenobarbital and beta-naphthoflavone rat liver. Test concentrations with justification for top dose:. - 5000, ... plate in the presence and absence of metabolic activation system from liver fraction of phenobarbital/beta-naphthoflavone- ... µg/plate in the presence and absence of metabolic activation system from liver fraction of phenobarbital/beta-naphthoflavone- ...
Adedoyin A, Aarons L, Houston JB (1993) Time-dependent disposition of beta-naphthoflavone in the rat. Pharm Res 10(1):35-43 ... Lund EG, Peterson LB, Adams AD et al (2006) Different roles of liver X receptor alpha and beta in lipid metabolism: effects of ... Foryst-Ludwig A, Clemenz M, Hohmann S et al (2008) Metabolic actions of estrogen receptor beta (ERbeta) are mediated by a ... Witkowski A, Joshi AK, Smith S (2002) Mechanism of the beta-ketoacyl synthase reaction catalyzed by the animal fatty acid ...
Coal dust alters beta-naphthoflavone-induced aryl hydrocarbon receptor nuclear translocation in alveolar type II cellsexternal ...
HODEK, P., KŘÍŽKOVÁ, J., FREI, E., SINGH, R., ARLT, V. M., STIBOROVÁ, M.; Impact of beta-naphthoflavone on genotoxicity of food ...
S9 microsomal fraction from rats induced with phenobarbitone/beta-naphthoflavone. Test concentrations with justification for ...
Dewa Y et al. Molecular expression analysis of beta-naphthoflavone-induced hepatocellular tumors in rats. Toxicol Pathol 37:446 ... Rashid S et al. Endosomal Adaptor Proteins APPL1 and APPL2 Are Novel Activators of {beta}-Catenin/TCF-mediated Transcription. J ...
The cellular localization of the EF1AB and CYP1A mRNA in the liver of control and beta-naphthoflavone treated fish was then ... The cellular localization of the EF1AB and CYP1A mRNA in the liver of control and beta-naphthoflavone treated fish was then ... Ten Atlantic salmon Salmo salar were intraperitoneally injected with 50 mg/kg of the strong CYP1A inducer beta-naphthoflavone ... Ten Atlantic salmon Salmo salar were intraperitoneally injected with 50 mg/kg of the strong CYP1A inducer beta-naphthoflavone ...
... beta-naphthoflavone and benzo(a)pyrene) treatment. Together they form a unique fingerprint. * beta-Naphthoflavone Medicine & ... beta-Naphthoflavone, sunflower seed oil, Naphthalene, β-Naphthoflavone, Stress, Brain monoamines, Cortisol, Rainbow trout, ... beta-naphthoflavone and benzo(a)pyrene) treatment. In: Aquatic Toxicology. 2008 ; Vol. 86, No. 3. pp. 341-351. ... beta-naphthoflavone and benzo(a)pyrene) treatment",. abstract = "We have investigated if treatment with two different PAHs such ...
This was not noted following pretreatment with beta-naphthoflavone. The authors conclude that OT binds to both Alb and Hb and ...
beta]-Naphthoflavone-Induced Mitochondrial Respiratory Damage in Cyp1 Knockout Mouse and in Cell Culture Systems: Attenuation ... beta]-hydroxysteroid dehydrogenase/isomerase.. Functional zonation of the rat adrenal cortex: the development and maintenance ...
Xenobiotic metabolism in Clara cells and alveolar type II cells isolated from lungs of rats treated with beta-naphthoflavone. ... Benzo(a)pyrene hydroxylase activity in enriched populations of Clara cells and alveolar type II cells from control and beta- ...
4-Hydroxy-alpha-naphthoflavone. 4-Hydroxy-beta-naphthoflavone. 4-Chlorochalcone. 4-Ethoxycoumarin. ...
Pretreatment of all nonhuman species studied with phenobarbital and beta-naphthoflavone and with Aroclor in rats produced ...
  • The effects of phenobarbital and beta-naphthoflavone on the elimination kinetics and metabolite pattern of caffeine in the beagle dog. (
  • Pretreatment of all nonhuman species studied with phenobarbital and beta-naphthoflavone and with Aroclor in rats produced distinctive inductive patterns. (
  • The expression and inducibility of cytochrome P450IA1 isozyme was investigated in the human carcinoma cell line Caco-2 cultured between days 7 and 35 in the absence or the presence of various enzyme inducers such as 3-methylcholanthrene, beta-naphthoflavone (beta NF), dioxin, isosafrole, rifampycin, dexamethasone or phenobarbital. (
  • Enzyme preparations from rats pretreated with p-448 dependent aryl-hydrocarbon hydroxylase (9037529) inducers (3- methylcholanthrene (MCA) (56495) and beta-naphthoflavone) and MCA treated responsive C57BL mice also metabolized quinoline to a mutagen, but phenobarbital (50066) and pregnenolone-16alpha- carbonitrile pretreatment did not yield active preparations. (
  • Kaliste Korhonen E, Tuovinen K, Hanninen O. Effect of phenobarbital and beta-naphthoflavone on activities of different rat esterases after paraoxon exposure. (
  • Super shift assays identified Jun-D and c-Fos proteins in the band-shift complexes observed with control and beta-naphthoflavone-treated Hepa-1 nuclear extracts. (
  • The cellular localization of the EF1AB and CYP1A mRNA in the liver of control and beta-naphthoflavone treated fish was then determined by in situ hybridization (ISH) using EF1AB and CYP1A biotinylated oligonucleotide probes. (
  • β-Naphthoflavone, also known as 5,6-benzoflavone, is a potent agonist of the aryl hydrocarbon receptor and as such is an inducer of such detoxification enzymes as cytochromes P450 (CYPs) and uridine 5'-diphospho-glucuronosyltransferases (UGTs). (
  • Ten Atlantic salmon Salmo salar were intraperitoneally injected with 50 mg/kg of the strong CYP1A inducer beta-naphthoflavone and liver tissue harvested seven days later. (
  • Beta-naphthoflovone and 3-methylcholantheren treated-fish developed 15-32 fold increase in Ethoxyresorufin-O-deethylase activity in liver microsomes. (
  • Exposure to certain chemicals, such as 3-methylcholanthrene, benzo[a]pyrene, beta-naphthoflavone, and oltipraz elevates UGT1A6 mRNA in liver and to a lesser extent gastrointestinal tract and kidney, but not in other tissues. (
  • Both class 1 and class 2 mRNAs were elevated in liver by 3-methylcholanthrene, benzo[a]pyrene, beta-naphthoflavone, and oltipraz, with preferential elevation of class 1 occurring after 3-methylcholanthrene and benzo[a]pyrene treatment. (
  • The liver from 10 control and 10 exposed fish were split into eight sections, RNA extracted and three reference (beta-actin, elongation factor 1AB (EF1AB)) and two detoxifying genes (CYP1A and GST) quantified with real-time RT-PCR. (
  • The study shows that genes encoding phase I and phase II conjugating enzymes are unevenly transcribed in different parts of the liver of Atlantic salmon seven days after a single-dose of beta-naphthoflavone exposure. (
  • The ISH data suggest that CYP1A transcription happens mainly in hepatocyte cells in the liver, and that hepatocytes in the vicinity of blood vessels respond stronger to beta-naphthoflavone than cells further away from the blood supply. (
  • Oxidative stress, liver biotransformation and genotoxic effects induced by copper in Anguilla anguilla L.--the influence of pre-exposure to beta-naphthoflavone. (
  • 1985, Effect of promethazine and isosafrole on rat-hepatic microsomal mono-oxygenase activity: comparison with classic inducers phenobarbitone and beta-naphthoflavone. (
  • We evaluated the dose-dependent induction of the cytochrome P4501A (CYP1A) system in the Sturgeon fish, Huso huso after after exposure to PAHs, beta-naphthoflavone (BNF) and 3- methylcholantheren. (
  • We have investigated if treatment with two different PAHs such as naphthalene (NAP) and benzo(a)pyrene (BaP), and the PAH-like Compound beta-naphthoflavone (BNF), may modify the stress responses elicited in rainbow trout by acute or prolonged stress stimuli, and the possible involvement of brain monoamines in those responses. (
  • This was not noted following pretreatment with beta-naphthoflavone. (
  • Pretreatment of chick embryos with beta-naphthoflavone, which causes a 90-fold increase in P450 1A levels, did not increase the formation of N-vinylPP after TTMS administration, showing that the heme moiety of P450 1A does not contribute to the formation of N-vinylPP. (
  • With links to view full text article, which is named "Anguilla anguilla L. oxidative stress biomarkers responses to copper exposure with or without beta-naphthoflavone pre-exposure. (
  • Three days before sacrifice, half of the rats in each group started daily intraperitoneal injections of the PAH, β-naphthoflavone (BNF). (
  • The lungs of other rats were homogenized and the microsomal fraction was isolated and assayed for basal and beta- naphthoflavone induced ethoxyresorufin-deethylase and ethoxycoumarin- deethylase (ECOD) activity. (
  • Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, CYP3As by rifampicin in heart regions and coronary arteries of pig. (
  • Expression and inducibility of CYP1A1, 1A2, 1B1 by beta-naphthoflavone and CYP2B22, 3A22, 3A29, 3A46 by rifampicin in the respiratory and olfactory mucosa of pig. (
  • On day 11, CYP1A1 was induced by intraperitoneal (IP) injection of 50 mg/kg beta-naphthoflavone (BNF). (
  • alpha-Naphthoflavone is a potent inhibitor of the enzyme aromatase, the enzyme that converts testosterone to estrogen. (
  • Neither a P450 1A selective inhibitor ({dollar}\alpha{dollar}-naphthoflavone) nor antibodies to rabbit P450 4B1 inhibited the formation of either class o{dollar}\sp-{dollar} metabolites. (
  • Human antioxidant-response element (hARE) containing two copies of the AP1/AP1-like elements arranged as inverse repeat is known to mediate basal and beta-naphthoflavone-induced transcription of the type 1 NAD(P)H:quinone oxidoreductase (NQO1) gene. (
  • beta-naphthoflavone induction of the CAT gene expression in Hepa-1 cells was found insensitive to inhibitors of protein kinase C and tyrosine kinases. (
  • Treatment of the Hepa-1 cells with N-ethylmaleimide reduced binding of proteins at the hARE and interfered with expression and beta-naphthoflavone induction of the CAT gene. (
  • Comparison to induction by the polyaromatic hydrocarbon, beta-naphthoflavone. (
  • The formation of these metabolites was not affected by {dollar}\beta{dollar}-naphthoflavone induction or P450 1A1 inhibitors demonstrating that P450 1A1 also does not contribute to arachidonic acid metabolism in guinea pig kidney. (
  • 4. Emborski C, Reyes A , Biggs J S. Effect of b-naphthoflavone on hepatic cytochrome P4501A activity in the scribbled rabbitfish (Siganusspinus) from tropical Indo-Pacific coral reefs. (
  • The inhibition of E-4-H activity by SKF-525A, metyrapone and alpha-naphthoflavone suggested involvement of cytochrome P450-dependent monooxygenases. (
  • Evidence from in vitro studies indicate the presence of unknown nuclear factor(s) that receive signals from metabolites of beta-naphthoflavone and modulate Jun and Fos binding to the AP1 site contained within the hARE. (
  • In addition, incubation of control nuclear extract with beta-naphthoflavone, microsomes and NADPH increased the binding of Jun and Fos proteins to the hARE. (
  • Data are now presented that show that administration of the anticarcinogen beta-naphthoflavone (BNF), like BHA, induces the Alpha-class 25,600-Mr subunits but not the constitutive Alpha-class GST with subunits of Mr 25,800. (
  • These data demonstrate that P450 2Bx is solely responsible for the metabolism of arachidonic acid to EETs in guinea pig lung and that a form of P450 other than 2Bx, 4Bx or 1A1, which is inducible by {dollar}\beta{dollar}-naphthoflavone, forms (16-20)-OH-AA. (
  • The fish were treated by i.p. injections of beta-naphthoflavone and 3- methylcholantheren dissolved in corn oil at three doses 35, 70 and 105 mg/kg wet-body weight respectively for 72 h every day. (
  • A single injection of estradiol-17 beta (E2, 100 ng/mouse) to ovariectomized mice significantly (P less than 0.01) elevated the level of E-4-H activity at 24 h as did injections of progesterone (P4, 2 mg/mouse) for 2 days. (
  • Juvenile sea bass biotransformation, genotoxic and endocrine responses to beta-naphthoflavone, 4-nonylphenol and 17 beta-estradiol individual and combined exposures. (
  • Adedoyin A, Aarons L, Houston JB (1993) Time-dependent disposition of beta-naphthoflavone in the rat. (
  • Beta-naphthoflavone (BNF) is protective against hyperoxic lung injury in adult and neonatal wild type (WT) mice and in and mice lacking Cyp1a1gene. (
  • Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-beta estradiol and nonylphenol. (
  • After a 3-day treatment of Caco-2 cells with 50 microM beta NF, EROD achieved 36.6 +/- 14.6 pmol/min/mg compared to 2.5 +/- 1.1 pmol/min/mg in untreated cells. (
  • 16-20)-OH-AA formation was increased by {dollar}\beta{dollar}-naphthoflavone treatment. (
  • Moreover, IFN-beta treatment may be useful in alleviating vascular leakage induced by ischemia-reperfusion injury. (
  • A parallel increase of the CYP1A immunochemically assay and an increase in EROD activity could be recorded for beta -naphthoflavone and 3- methylcholantheren in injected fish. (
  • Hepa-1 cells stably transformed with hARE-tk-chloramphenicol acetyl transferase (CAT) recombinant plasmid were used to demonstrate that, in addition to beta-naphthoflavone, a variety of antioxidants, tumor promoters and hydrogen peroxide (H2O2) also increased expression of hARE-mediated CAT gene. (
  • Combining inhaled glucocorticoids and generic cialis no doctor's prescription long acting beta(2)-adrenoceptor agonists in asthma and COPD. (
  • Only beta-naphthoflavone decreased nasal olfactory epithelial damage. (
  • Leivonen S, Chantry A, Hakkinen L, Han J, Kahari V. Smad3 mediates transforming growth factor-beta-induced collagenase-3 (matrix metalloproteinase-13) expression in human gingival fibroblasts. (
  • Band-shift assays revealed that beta-naphthoflavone increased binding of nuclear proteins at the hARE. (
  • The incubation of Jun and Fos proteins with small amounts of nuclear extract from dimethylsulfoxide-treated (control) or beta-naphthoflavone treated Hepa-1 cells prior to band-shift assays increased the binding of Jun and Fos proteins to the hARE. (
  • Interestingly, the increase in binding of Jun and Fos proteins to the hARE was more prominent with beta-naphthoflavone-treated nuclear extract as compared to the control nuclear extract. (
  • The metabolism of flutamide is inhibited by low concentrations of alpha-naphthoflavone and ketoconazole. (
  • The mutagenicity of quinoline was blocked by the in-vitro addition of menadione (58275), butylated-hydroxytoluene (128370), alpha- naphthoflavone, vitamin A acetate, and glutathione (70188) to the test system. (
  • alpha-Naphthoflavone has been shown to cause abnormal testicular development in young chickens. (
  • dollar} 4Bx whereas in {dollar}\beta{dollar}-naphthoflavone-induced animals {dollar}\alpha{dollar}MB specifically inhibited 2Bx. (
  • β-Naphthoflavone is a putative chemopreventive agent. (
  • Reductions in 17beta-estradiol-induced vitellogenin levels were observed in white sturgeon co-injected with beta-naphthoflavone (BNF, 50 mg/kg), an Ah receptor agonist. (