Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Fungal: The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Grateful Med: A microcomputer-based software package providing a user-friendly interface to the MEDLARS system of the National Library of Medicine.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Antitubercular Agents: Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Vascular Resistance: The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Tuberculosis, Multidrug-Resistant: Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Class II Phosphatidylinositol 3-Kinases: A subclass of phosphatidylinositol 3-kinases that have specificity for 1-phosphatidylinositol and 1-phosphatidylinositol 4-phosphate. Members of this subclass consist of a single subunit structure and are regulated by RECEPTOR TYROSINE KINASES; CYTOKINE RECEPTORS; and INTEGRINS.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Frameshift Mutation: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Polymerase Chain Reaction: 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.HIV Protease: Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.Cathepsin H: An ubiquitously-expressed lysosomal cysteine protease that is involved in protein processing. The enzyme has both endopeptidase and aminopeptidase activities.HIV Reverse Transcriptase: A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.Multidrug Resistance-Associated Proteins: A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.Cell Line, Tumor: A cell line derived from cultured tumor cells.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Mycobacterium tuberculosis: A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Escherichia coli: 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.Bacterial Proteins: Proteins found in any species of bacterium.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.R Factors: A class of plasmids that transfer antibiotic resistance from one bacterium to another by conjugation.Streptomycin: An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.Genes, MDR: Genes for MEMBRANE TRANSPORT PROTEINS that confer resistance to toxic compounds. Several superfamilies of these multidrug export proteins are known and found in both prokaryotes and eukaryotes.Tetracycline Resistance: Nonsusceptibility of bacteria to the action of TETRACYCLINE which inhibits aminoacyl-tRNA binding to the 30S ribosomal subunit during protein synthesis.Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.Drug Resistance, Multiple, Fungal: The ability of fungi to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutations.Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins.Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Tetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.Plant Diseases: Diseases of plants.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Orexin Receptors: G-protein-coupled NEUROPEPTIDE RECEPTORS that have specificity for OREXINS and play a role in appetite control, and sleep-wake cycles. Two principle receptor types exist, each having a specificity for OREXIN A and OREXIN B peptide subtypes.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Plasmodium falciparum: A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.Parasitic Sensitivity Tests: Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites.Genes, Bacterial: The functional hereditary units of BACTERIA.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Conjugation, Genetic: A parasexual process in BACTERIA; ALGAE; FUNGI; and ciliate EUKARYOTA for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a uni-directional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes.Mutation Rate: The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.Tumor Cells, Cultured: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Apoptosis: 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.DNA Primers: 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.Pyrimethamine: One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Signal Transduction: 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.HIV Protease Inhibitors: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.Reverse Transcriptase Polymerase Chain Reaction: 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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.beta-Lactam Resistance: Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets.Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Resistance Training: A type of strength-building exercise program that requires the body muscle to exert a force against some form of resistance, such as weight, stretch bands, water, or immovable objects. Resistance exercise is a combination of static and dynamic contractions involving shortening and lengthening of skeletal muscles.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Genetic Variation: Genotypic differences observed among individuals in a population.Tetrahydrofolate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.Malaria, Falciparum: Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.RNA, Messenger: 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.Antiviral Agents: Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.Sulfadoxine: A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.Chloramphenicol Resistance: Nonsusceptibility of bacteria to the action of CHLORAMPHENICOL, a potent inhibitor of protein synthesis in the 50S ribosomal subunit where amino acids are added to nascent bacterial polypeptides.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.Ampicillin Resistance: Nonsusceptibility of a microbe to the action of ampicillin, a penicillin derivative that interferes with cell wall synthesis.pol Gene Products, Human Immunodeficiency Virus: Proteins encoded by the POL GENE of the HUMAN IMMUNODEFICIENCY VIRUS.Models, Biological: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.DNA-Binding Proteins: 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.Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.DNA Transposable Elements: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.DNA Gyrase: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Erythromycin: A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.Membrane Proteins: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Azoles: Five membered rings containing a NITROGEN atom.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Protozoan Proteins: Proteins found in any species of protozoan.Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.P-Glycoproteins: A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.Chloramphenicol: An antibiotic first isolated from cultures of Streptomyces venequelae in 1947 but now produced synthetically. It has a relatively simple structure and was the first broad-spectrum antibiotic to be discovered. It acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. (From Martindale, The Extra Pharmacopoeia, 29th ed, p106)Anti-Retroviral Agents: Agents used to treat RETROVIRIDAE INFECTIONS.Blotting, Western: 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.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Sequence Alignment: 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.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Genes, MDR: Genes for MEMBRANE TRANSPORT PROTEINS that confer resistance to toxic compounds. Several superfamilies of these multidrug export proteins are known and found in both prokaryotes and eukaryotes.Dihydropteroate Synthase: An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. EC 2.5.1.15.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Candida albicans: A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis).Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Methicillin Resistance: Non-susceptibility of a microbe to the action of METHICILLIN, a semi-synthetic penicillin derivative.Kinetics: The rate dynamics in chemical or physical systems.Homozygote: An individual in which both alleles at a given locus are identical.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Extrachromosomal Inheritance: Vertical transmission of hereditary characters by DNA from cytoplasmic organelles such as MITOCHONDRIA; CHLOROPLASTS; and PLASTIDS, or from PLASMIDS or viral episomal DNA.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Vulvodynia: Complex pain syndrome with unknown etiology, characterized by constant or intermittent generalized vulva pain (Generalized vulvodynia) or localized burning sensations in the VESTIBULE area when pressure is applied (Vestibulodynia, or Vulvar Vestibulitis Syndrome). Typically, vulvar tissue with vulvodynia appears normal without infection or skin disease. Vulvodynia impacts negatively on a woman's quality of life as it interferes with sexual and daily activities.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins.Mutagenesis, Insertional: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.Breast Neoplasms: Tumors or cancer of the human BREAST.Macrolides: A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.Artemisinins: A group of SESQUITERPENES and their analogs that contain a peroxide group (PEROXIDES) within an oxepin ring (OXEPINS).Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Viral Load: The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a SURROGATE MARKER in disease progression.Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.Tuberculosis: Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.Fungal Proteins: Proteins found in any species of fungus.Insulin: 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).Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Tuberculosis, Pulmonary: MYCOBACTERIUM infections of the lung.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Vancomycin Resistance: Nonsusceptibility of bacteria to the action of VANCOMYCIN, an inhibitor of cell wall synthesis.Vault Ribonucleoprotein Particles: Large cytoplasmic ribonucleoprotein particles that have an eight-fold symmetry with a central pore and petal-like structure giving the appearance of an octagonal dome. (The Dictionary of Cell Biology, Lackie and Dow, 2nd ed.)Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Promoter Regions, Genetic: 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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.Antibiotics, Antitubercular: Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.DNA Topoisomerases, Type II: DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Cells, Cultured: 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.Cephalosporin Resistance: Non-susceptibility of an organism to the action of the cephalosporins.PiperazinesPolyomavirus: A genus of potentially oncogenic viruses of the family POLYOMAVIRIDAE. These viruses are normally present in their natural hosts as latent infections. The virus is oncogenic in hosts different from the species of origin.Antiretroviral Therapy, Highly Active: Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.Malaria: A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.Crosses, Genetic: Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.HIV: Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.Folic Acid Antagonists: Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.Structure-Activity Relationship: 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.Mice, Inbred C57BL
The most common mutation observed in vivo is L74V in the viral pol gene, which confers cross-resistance to zalcitabine; other ... "Use of viral resistance patterns to antiretroviral drugs in optimising selection of drug combinations and sequences". Drugs. 52 ... Drug resistance to didanosine does develop, though slower than to zidovudine (AZT). ... The related pro-drug of didanosine, 2′,3′-dideoxyadenosine (ddA), was initially synthesized by Morris J. Robins (professor of ...
... the virus has likely developed resistance to the ARVs. As more and more drug-resistance conferring mutations develop in the ... If the patient's viral load (the amount of HIV in the blood) rebounds after being suppressed by ARVs, ... Salvage therapy drugs or drug combinations have, in general, much more severe side effects than the standard line of therapy. ... This is often true of a drug of last resort. Antiretroviral drugs (ARVs) are given to slow down the HIV reproduction, which in ...
... but others can confer evolutionary advantages such as resistance to antiviral drugs. Antigenic shift occurs when there is a ... Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R. Viral mutation rates. Journal of Virology. 2010;84(19):9733-48. doi: ... One of the most effective is the presence of so-called resistance (R) genes. Each R gene confers resistance to a particular ... viral protein synthesis, possible assembly of viral proteins, then viral genome replication mediated by early or regulatory ...
... was chosen not only for genetic compatibility but also for being homozygous for a CCR5-Δ32 mutation that confers resistance to ... further simplifying drug regimens to improve adherence, and determining better sequences of regimens to manage drug resistance ... According to the researchers, this approach could lead to a dramatic reduction of the viral load in patient cells.[29][30] ... In both cases, the drugs would be the same as those used to treat persons with HIV, and the intent of taking the drugs would be ...
This is a result of the bone marrow donor being homozygous for the CCR5-Δ32 mutation. This new mutation conferred a resistance ... A viral vector is used to deliver the ZFNs that induce the desired mutation into the cells. Conditions that promote this ... After nearly 2 years without antiretroviral drug therapy, HIV could still not be detected in any of his tissues. Though this ... while those that are heterozygous for this mutation have been found to reduce plasma viral load and delay progression of AIDS. ...
... including a common mutation that confers drug resistance (with William Pao[18]); and generation of numerous mouse models of ... triggered the identification of many other cellular proto-oncogenes-progenitors of viral oncogenes and targets for mutations ... Director, Office of National Drug Control Policy. Gil Kerlikowske. 2009-14. Angella Reid. 2011-17. Michael Botticelli. 2014-17 ... characterization of mutations of the epidermal growth factor receptor gene in human lung cancers, ...
... his research on HIV-1 drug resistance identified one of the essential reverse transcriptase (RT) mutations conferring ... Paul Kellam (born 13 September 1965) is the Virus Genomics team leader and is a Professor of Viral Pathogenesis at University ... and determined that retroviral recombination resulted in the genetic linkage of mutations conferring high-level drug resistance ... and this identified how the development of multiple mutations lead to high-level resistance to antiviral drug regimes. Kellam's ...
... designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation ... In January 2008, the Food and Drug Administration approved its use for patients with established resistance to other drugs, ... who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) ... resistance to other NNRTIs does not seem to confer resistance to etravirine. Etravirine is marketed by Tibotec, a subsidiary of ...
Thus oseltamivir prevents new viral particles from being released. The vast majority of mutations conferring resistance are ... "Antiviral Drug Resistance among Influenza Viruses Guidance on the Use of Influenza Antiviral Agents (Current for the 2013-14 ... As of 2013[update] H274Y and N294S mutations that confer resistance to oseltamivir have been identified in a few H5N1 isolates ... Three studies have found resistance in 0%, 3.3%, and 18% of subjects. In the study with the 18% resistance rate, the subjects ...
Because "most of HIV strains" use the CCR5 receptor to enter a host cell, the mutation confers resistance to HIV infection.[3][ ... There is no virus in this person's body out to two and a half years off of all anti-HIV drugs. His antibody levels-called ... "could pave the way for innovative approaches that provide long-lasting viral control with limited toxicities for persons with ... The physicians found a bone marrow donor with a CCR5-Δ32 mutation in both genomic copies of a gene encoding a cell-surface ...
Other mutations including insertions and deletions in the background of the above mutations also confer resistance via enhanced ... 2001). "The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance". Journal of Molecular Biology. 309 (2): 437- ... reverse transcriptase copies the viral single stranded RNA genome into a double-stranded viral DNA. The viral DNA is then ... "Update of the drug resistance mutations in HIV-1: December 2009". Topics in HIV medicine : a publication of the International ...
Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials.[72] Cross-resistance ... Resistance and modifying agentsEdit. One strategy to address bacterial drug resistance is the discovery and application of ... Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extra-chromosomal DNA.[68] ... Inappropriate antibiotic treatment, for example, is their prescription to treat viral infections such as the common cold. One ...
... often associated with amino acid substitutions that confer upon the virus a robust drug resistance without impairing the viral ... Nakamoto, Shingo (2014). "Hepatitis C virus NS5A inhibitors and drug resistance mutations". World Journal of Gastroenterology. ... The potential HCV resistance against DAA drugs is a concern. Among the HCV quasispecies there are pre-existing variants with ... the potential to confer resistance to NS5A inhibitors without having any previous exposure to those drugs. Generally, the ...
The viral polymerase incorporates these compounds with non-canonical bases. These compounds are activated in the cells by being ... This results in a change in one base pair of DNA, specifically a transition mutation. Commonly fluorophores (such as rhodamine ... Cordycepin is an anticancer drug that targets RNA replication. Another analogue in sequencing is a nucleobase analogue, 7-deaza ... Typically the analogue nucleobases confer, among other things, different base pairing and base stacking properties. Examples ...
Thus, tumor vessels have the theoretical potential for developing acquired resistance to drugs. This is a new area of ... This genomic stability confers an advantage to targeting endothelial cells using antiangiogenic therapy, compared to ... A malignant tumor consists of a population of rapidly dividing and growing cancer cells that progressively accrues mutations. ... and oncogenesis related to the viral vectors used in implanting genes and the sheer complexity of the genetic basis of ...
Transgenic trees have been suggested as a way to confer resistance to pathogens in wild populations. With the increasing risks ... Cows and goats have been engineered to express drugs and other proteins in their milk, and in 2009 the FDA approved a drug ... When this is done by creating a library of genes with point mutations at every position in the area of interest, or even every ... Gene transfer through viral vectors has been proposed as a means of controlling invasive species as well as vaccinating ...
Flu drugs Tamiflu and Relenza work by inhibiting some strains of neuraminidase. They were developed based on N2 and N9. "In the ... PA genes code for the PA protein, which is a critical component of the viral polymerase. The PB1 gene codes for the PB1 protein ... But he pointed out that one mutation is not sufficient to turn H5N1 into a major threat to humans. "Archived copy". Archived ... leading to the possibility that the annual flu shot or Flumist inoculation might confer some immunity against H5N1 bird flu ...
... which confers kanamycin-resistance, as oftentimes parenthetically noted for drug-resistance markers) When referring to the ... rifampicin resistance tonA = phage T1 resistance sup = suppressor (for instance, supF suppresses amber mutations) If the gene ... the symbol for the gene v-akt murine thymoma viral oncogene homolog 1, which is AKT1, cannot be said to be an acronym for the ... ampicillin resistance azi = azide resistance bla = beta-lactam resistance cat = chloramphenicol resistance kan = kanamycin ...
These records of built up resistance infer that drugs, such as adamantine, will not be useful against the influenza virus in ... 2007). "The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance". Molecular ... These mutations lead to subtle changes in the HA and NA genes which completely changes the infectious capabilities of the virus ... These changes allow for almost endless possibilities for new viral strains to arise and it is the antigenic drift of the HA and ...
... mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral ... Flu drugs Tamiflu and Relenza work by inhibiting some strains of neuraminidase. They were developed based on N2 and N9. "In the ... The amino acid substitution (Ser31Asn) in M2 some H5N1 genotypes is associated with amantadine resistance. NP codes for ... Lys at PB2-627 is believed to confer to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory ...
"Amino Acid Substitutions At Residue 207 of Viral Capsid Protein 1 (VP1) Confer Pleconaril Resistance in Coxsackievirus B3 (CVB3 ... The Ile->Leu mutation causes complete resistance to pleconaril. The study found resistance of CVB3 to pleconaril can be ... The other strain was susceptible to the drug. The pleconaril group had 21 virus strains, which remained susceptible. Resistance ... ViroPharma developed it further, and submitted a New Drug Application to the United States Food and Drug Administration (FDA) ...
... which confers intrinsic resistance to the NNRTI class. Resistance to nevirapine develops rapidly if viral replication is not ... A major concern with this approach is that NNRTI resistance mutations are commonly observed in both mothers and infants after ... Conway B, Wainberg MA, Hall D (Jul 2001). "Development of drug resistance in patients receiving combinations of zidovudine, ... Cases of immune reconstitution syndrome and fat redistribution have also been observed with this drug. U.S. Food and Drug ...
... stress resistance, herbicide resistance, pest resistance, production of useful goods such as biofuel or drugs, and ability to ... Wang, Yanpeng (2014). "Simultaneous editing of three homoeoalleles in hexaploid bread wheat confers heritable resistance to ... found also viral genes in transgenic plants. Transgenic carrots have been used to produce the drug Taliglucerase alfa which is ... Plant tissue culture and deliberate mutations have enabled humans to alter the makeup of plant genomes. The first genetically ...
... which confers intrinsic resistance to the NNRTI class. As most NNRTIs bind within the same pocket, viral strains which are ... People who are taking both efavirenz and other drugs metabolized by the same enzymes might need the dose of their drugs to be ... The most common mutation observed after efavirenz treatment is K103N, which is also observed with other NNRTIs. Nucleoside ... As a result of lowered levels, antifungal drugs may not be effective in people taking both drugs, which means that the fungi ...
... using antibiotics longer than necessary helps preventing bacteria from forming mutations that aide in antibiotic resistance. ... Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family. ... When infection attacks the body, anti-infective drugs can suppress the infection. Several broad types of anti-infective drugs ... these natural antibodies confer specific protection to adults and are passively transmitted to newborns. The organism that is ...
... (also spelled sulphadoxine) is an ultra-long-lasting sulfonamide used in combination with pyrimethamine to treat malaria. It was previously used to prevent malaria but due to high levels of resistance, this use is no longer recommended routinely. It is also used, usually in combination with other drugs, to treat or prevent various infections in livestock.[citation needed] Sulfadoxine competitively inhibits dihydropteroate synthase, interfering with folate synthesis. Sulfadoxine/pyrimethamine Medical Treatment - Sulphadoxine and Pyrimethamine. Matondo SI, Temba GS, Kavishe AA, et al. (2014). "High levels of sulphadoxine-pyrimethamine resistance Pfdhfr-Pfdhps quintuple mutations: a cross sectional survey of six regions in Tanzania". Malar J. 13: 152. doi:10.1186/1475-2875-13-152. PMC 3998221 . PMID 24751352 ...
... is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in curing a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant. Even the immune system of an organism is in essence a drug delivery system, albeit endogenous, and faces the same arms race problems as external drug delivery. The development of antibiotic resistance in particular stems from the drugs ...
ସଲଫାଡକ୍‌ସିନ/ପାଇରିମେଥାମିନ (ଇଂରାଜୀ ଭାଷାରେ Sulfadoxine/pyrimethamine, ବିକ୍ରୟ ନାମ ଫାନ୍‌ସିଡାର/Fansidar) ଏକ ଯୁଗ୍ମ ଔଷଧ ଯାହା ମ୍ୟାଲେରିଆ ରୋଗର ଚିକିତ୍ସା ପାଇଁ ଦିଆଯାଏ ।[୧][୨] ଏହି ଯୁଗ୍ମ ଔଷଧରେ ସଲଫାଡକ୍‌ସିନ (sulfadoxine) ନାମ ଥିବା ଏକ ପ୍ରକାର ସଲଫୋନାମାଇଡ (sulfonamide) ଓ ପାଇରିମେଥାମିନ (pyrimethamine) ଭଳି ଏକ ପ୍ରୋଟୋଜୋଆ ବିରୋଧୀ (antiprotozoal) ଔଷଧ ଥାଏ । ଏହା ଆର୍ଟେସୁନେଟ ଭଳି ମ୍ୟାଲେରିଆ ବିରୋଧୀ (antimalarial medication ) ଔଷଧମାନଙ୍କ ସ‌ହିତ ଦିଆଯାଏ ।[୩] ସଲଫାଡକ୍‌ସିନ/ପାଇରିମେଥାମିନର ପାର୍ଶ୍ୱ ...
A resistance movement is an organized effort by some portion of the civil population of a country to resist the legally established government or an occupying power and to disrupt civil order and stability. It may seek to achieve its objectives through either the use of nonviolent resistance (sometimes called civil resistance), or the use of force, whether armed or unarmed. In many cases, as for example in Norway in the Second World War, a resistance movement may employ both violent and non-violent methods, usually operating under different organizations and acting in different phases or geographical areas within a country.[1]. The term resistance is generally used to designate a movement considered legitimate (from the speaker's point of view). Organizations and individuals critical of foreign intervention and supporting forms of organized ...
... (NRTIs and NtRTIs) began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs. In the summer of 1981 the acquired immunodeficiency syndrome (AIDS) was first reported. Two years later the etiological link to AIDS, the human immunodeficiency virus (HIV) was identified. Since the identification of HIV the development of effective antiretroviral ...
... (INN) is an HIV fusion inhibitor, the first of a novel class of antiretroviral drugs used in combination therapy for the treatment of HIV-1 infection. It is marketed under the trade name Fuzeon (Roche). Enfuvirtide therapy costs an estimated US$25,000 per year in the United States. Its cost and inconvenient dosing regimen are factors behind its use as a reserve, for salvage therapy in patients with multi-drug resistant HIV. Ac-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu-Ile-Glu-Glu-Ser-Gln-Asn-Gln-Gln-Glu-Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn-Trp-Phe-NH2 Enfuvirtide originated at Duke University, where researchers formed a pharmaceutical company known as Trimeris. Trimeris began development on enfuvirtide in 1996 and initially designated it T-20. In 1999, Trimeris entered into partnership with Hoffmann-La Roche to complete the development of the drug. It was approved ...
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV). NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV. RT is one of the most popular targets in the field of antiretroviral drug development. Discovery and development of NNRTIs began in the late 1980s and in the end of 2009 four NNRTI had been approved by regulatory authorities and several others were undergoing clinical development. Drug resistance develops quickly if NNRTIs are administered as monotherapy and therefore NNRTIs are always given as part of combination therapy, the highly active antiretroviral therapy (HAART). Acquired immunodeficiency syndrome (AIDS) is a leading cause of death in the world. It was identified ...
... (ETR,[1] brand name Intelence, formerly known as TMC125) is a drug used for the treatment of HIV. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine.[2] Etravirine is marketed by Tibotec, a subsidiary of Johnson & Johnson. In January 2008, the Food and Drug Administration approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008.[3] It was also approved for use in Canada on April 1, 2008.[4]. Etravirine is licensed in the United States, Canada, Israel, Russia, Australia and the European Union,[5] and is under ...
Aseksuaalsena võivad määratleda väga erinevad inimesed. Seetõttu võivad aseksuaalsuse definitsioonid olla suhteliselt laiad.[13] Uurijad määratlevad üldiselt aseksuaalsust seksuaalse külgetõmbe või seksuaalse huvi puudumisena.[14][15][16] Samas nende definitsioonid varieeruvad: nad võivad kasutada mõistet, et "viidata isiku madalale või puuduvale seksuaalsele ihale või külgetõmbele, madalale või puuduvale seksuaalsele käitumisele, eksklusiivselt romantilisele mitteseksuaalsele suhtele või puuduva seksuaalse iha ja käitumise kombinatsioonile."[16][17] Enesemääratlus aseksuaalsusena võib olla määramisel otsustavaks teguriks.[17] AVEN defineerib aseksuaalset inimest kui "kedagi, kes ei koge seksuaalset külgetõmmet". Nad lisavad, et "väike osa inimestest peab end aseksuaalseks lühikest aega, kui nad uurivad ja avastavad enda seksuaalsust". AVEN-i järgi "ei ole määravat faktorit, mille alusel kindlaks teha, kas keegi on aseksuaalne. Aseksuaalne on oma olemuselt nagu ...
Hodgkini lümfoomi levinuimad sümptomid on kaela, kaenlaaluse või vaagna piirkonnas paikneva ühe või mitme lümfisõlme, harilikult valutu, suurenemine. Lümfoomi korral suurenevad lümfisõlmed aeglaselt ja võib kuluda kuid või aastaid, enne kui neid märgatakse. Mõnikord võivad lümfisõlmed suureneda väga kiiresti.[11] Rohkem kui 80%-l patsientidest on leitud lümfadenopaatia ülalpool diafragmat.[2] Kolmandikul (25%) patsientidest esineb Hodgkini lümfoomi korral ka üldsümptomeid (nn B-sümptomid), näiteks öine higistamine, kõrge kehatemperatuur, mis tõuseb ja alaneb spontaanselt, märgatav kaalukaotus lühikese aja jooksul, sügelemine, mis võib pärast alkoholi seespidist tarbimist intensiivistuda, köha või hingeldus, kõhuvalu või oksendamine pärast alkoholi joomist.[11] ...
Logistiline regressioon saab olla nii binaarne, järjestatud või multinomiaalne. Binoomse või binaarse logistilise regressiooni puhul uuritakse olukorda, kus uuritaval tunnusel on kaks võimalikku väärtust: 0 ja 1. Multinominaalse regressiooni puhul on tegemist olukorraga, kus väljundiks on 3 või rohkem sõltumatut väärtust ning väärtustel puudub järjestus. Järjestatud logistilise regressiooni korral uuritakse tunnust, millel on mitu sõltuvat taset ning tasemed on järjestatud. Logit-mudel on kõige enam kasutatud meetod binaarse tunnuse modelleerimiseks. Sellel on ühtlasi ka kerge ja arusaadav interpretatsioon[5]. Sündmuse toimumisel ("ravimi tarvitamine", "võit" jne.) märgitakse tavaliselt "1" ning vastandsündmuse ("platseebo tarvitamine", "kaotus" jne) korral vastavalt "0". Mudeli parameetrite interpreteerimisel kasutatakse šansside suhte muutusi, kust sündmuse šanss on defineeritud kui sündmuse esinemise tõenäosuse ja sündmuse mitteesinemise tõenäosuse suhe. ...
Inimese kloonimine tähendab olemasolevast või varem eksisteerinud inimesest geneetiliselt identse koopia loomist. Seda mõistet kasutatakse tavaliselt selleks, et määratleda inimese kunstlikku kloonimist. Loomuliku paljunemise ajal võib toimuda samuti kloonimine, selle tulemusena sünnivad identsed kaksikud. Eristatakse kahte inimkloonimist - üks on terapeutiline kloonimine ja teine reproduktiivne kloonimine. Teoreetiliselt on võimalik ka kolmas koonimise variant, kus ühendatakse nii terapeutiline kui ka reproduktiivne kloonimine. Seda kutsutakse asenduskloonimiseks. See tähendaks ulatuslikult kahjustunud kehaosa asendamist, millele järgneks osaline või täielik ajusiirdamine. Erinevad inimkloonimise tüübid on tekitanud palju vaidlusi.[24] Enamik teadus-, valitsus- ja usuorganisatsioone on rangelt reproduktiivse kloonimise vastu. Ameerika Ühendriikide teaduse edendamise liit (AAAS) ja paljud teised teadusühingud on teinud avaldusi, et inimese kloonimine tuleks keelustada seni, ...
Asendamatuteks rasvhapeteks kutsutakse neid rasvhappeid, mis on inimesele vajalikud, kuid mida inimese organism suudab vaid väheses koguses ise toota ja seega peab ta neid saama toidust. On kahte tüüpi asendamatuid rasvhappeid: need, kus kaksikside asub kolme süsinikuaatomi kaugusel ahela lõpus olevast metüülrühmast, ja need, kus kaksikside asub kuue süsinikuaatomi kaugusel ahela lõpus olevast metüülrühmast. Inimese organismil puudub võime sünteesida rasvhappeid, kus kaksiksidemed asuvad karboksüülrühmast loendatult kaugemal kui 9. või 10. süsinikuaatomi juures.[7] Asendamatud rasvhapped on näiteks linoolhape ja linoleenhape, mida leidub paljudes taimeõlides. Inimese võime muuta linoleenhape pikema ahelaga oomega-3-rasvhappeks (nt eikosapentaeenhappeks või dokosaheksaeenhappeks) on piiratud, aga ta saab neid rasvhappeid omastada kalast. ...
V106M may be a signature mutation in clade C patients treated with EFV and may have the potential to confer high-level multi- ... Drug Resistance, Viral / genetics * HIV Reverse Transcriptase / antagonists & inhibitors * HIV-1 / drug effects ... A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase ... resistance-conferring mutations in B (n = 440) and non-B (n = 84) clinical isolates. Cell-based phenotypic assays were ...
A dominant mutation in the Wilms tumor gene WT1 cooperates with the viral oncogene E1A in transformation of primary kidney ... Wilms Tumor (WT1) Gene Mutations Occur Mainly in Acute Myeloid Leukemia and May Confer Drug Resistance. L. King-Underwood and ... Wilms Tumor (WT1) Gene Mutations Occur Mainly in Acute Myeloid Leukemia and May Confer Drug Resistance. Blood, 91(8), 2961- ... Wilms Tumor (WT1) Gene Mutations Occur Mainly in Acute Myeloid Leukemia and May Confer Drug Resistance ...
The most common mutation observed in vivo is L74V in the viral pol gene, which confers cross-resistance to zalcitabine; other ... "Use of viral resistance patterns to antiretroviral drugs in optimising selection of drug combinations and sequences". Drugs. 52 ... Drug resistance to didanosine does develop, though slower than to zidovudine (AZT). ... The related pro-drug of didanosine, 2′,3′-dideoxyadenosine (ddA), was initially synthesized by Morris J. Robins (professor of ...
... mutation in the genome confers low-level or high-level resistance or does not confer any resistance to the antiviral drugs at ... Studies of transplant recipients and of patients infected with human immunodeficiency virus suggest that mutations in the viral ... and mutations at codons 981 to 987 appear to confer simultaneous mutations to the three drugs. Most UL54 mutations are ... mutations at codons 375 to 540 confer ganciclovir and cidofovir cross-resistance, mutations at codons 756 to 809 confer ...
However, the difficult treatment regimens, the presence of class-specific drug toxicities, and the emergence of drug-resistant ... while making drugs that can be used throughout both the developed and developing world, in pediatric populations, and in ... and the development of increasingly potent molecules within existing classes of drugs and the development of novel strategies ... virus isolates highlight the fact that improvements in our therapeutic regimens and the identification of new and novel viral ...
... a team led by Stanford graduate student Alison Feder has examined the population dynamics of that resistance. Their work, ... Mutations conferring resistance had popped up repeatedly and independently in a variety of viral genomes. ... These drugs were vulnerable to only a few viral mutations, so when one developed, it was one of the only surviving viral ... That is, each person infected harbored a diverse viral population even after they had developed resistance to the drug. ...
... but did not accumulate mutations conferring drug resistance. Previous work had suggested that antiretroviral drug ... drug-sensitive HIV strains tend to dominate over drug-resistant strains when the effective drug concentration is low. At ... Future studies using drugs that better penetrate the entire lymphoid tissue compartment should provide a more complete picture ... A better understanding of how HIV persists in the body is essential for developing strategies to eliminate viral reservoirs-a ...
... recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi ... Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly ... Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of ... single mutations confer only a modest reduction in drug susceptibility. ...
... the virus has likely developed resistance to the ARVs. As more and more drug-resistance conferring mutations develop in the ... If the patients viral load (the amount of HIV in the blood) rebounds after being suppressed by ARVs, ... Salvage therapy drugs or drug combinations have, in general, much more severe side effects than the standard line of therapy. ... This is often true of a drug of last resort. Antiretroviral drugs (ARVs) are given to slow down the HIV reproduction, which in ...
Low numbers of drug-resistant viruses carrying the H274Y mutation usually followed oseltamivir treatment and showed reduced ... in the NA protein that confers high-level resistance to oseltamivir (2). Further surveillance by the European Surveillance ... Network for Vigilance against Viral Resistance and the WHO Global Influenza Surveillance Network (GISN) showed that 16% of ... Partial sequencing of the NA and hemagglutinin (HA) genes was performed to confirm the NA H274Y resistance mutation and to ...
... but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. ... While previous work has shown that TNTs facilitate the exchange of viral or prion proteins from infected to naive cells, it is ... but disruptions and mutations in chromosomal loci (i.e. mgrB and pmrB) previously reported to confer colistin resistance were ... Without these two drugs, tuberculosis is very difficult and costly to treat, with unacceptably high rates of treatment failure ...
... drug concentrations are major predictors of treatment failure and the emergence of viral mutations that confer resistance. ... and personal beliefs about the safety and efficacy of the drugs (1, 2). Drug level may also be influenced by coadministration ... Nonadherence seems the most common reason for suboptimal drug levels (1). The ability of patients to adhere to antiretroviral ... of medications and nontraditional treatments that induce the metabolism or efflux pumping of antiretroviral drugs (3). In ...
... Learn about HIV, its treatment, and how to take care of ... but did not accumulate mutations conferring drug resistance. Previous work had suggested that antiretroviral drug ... drug-sensitive HIV strains tend to dominate over drug-resistant strains when the effective drug concentration is low. At ... Future studies using drugs that better penetrate the entire lymphoid tissue compartment should provide a more complete picture ...
It is in this milieu that new mutations that might confer advantage, such as drug resistance, arise. A recent emphasis is to ... Cell Biology, Genetics and Biochemistry of RNA Viral Propagation For many subcellular viruses and parasites, RNA, not DNA, is ... Genetically, this process is highly error-prone, due to the low fidelity of the viral RNA polymerases. This low fidelity ... learn how to suppress the diversity of such viruses, and the outgrowth of potentially drug-resistant viruses, by understanding ...
... drug-resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo ... Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the ... raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against ... Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in ,1% of the viral ...
... the polymorphisms do not confer drug resistance but may change the "genetic barrier," which is defined as the number of viral ... A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase ... These polymorphisms, if conferring drug resistance, can be selected by drug-selective pressure and dramatically influence the ... The impact of the M184V substitution on drug resistance and viral fitness. Expert Rev. Anti Infect. Ther. 2:147-151. ...
... which reduce the clinical benefits conferred by that agent. One crucial obstacle in curbing drug resistance is that once it has ... A key driver of resistance is that drug resistance mutations often persist even in the absence of drugs and despite the fact ... A key driver of resistance is that drug resistance mutations often persist even in the absence of drugs and despite the fact ... Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS ONE. 2009; 4:e4724. doi: ...
For example, the M2 mutation S31N is now present in ,90% of influenza strains and confers resistance to adamantanes. Thus new ... A proven influenza antiviral target is the M2 viroporin, or viral ion channel. Amantadine, an M2 inhibitor was an effective ... Design and synthesis of novel influenza M2 proton channel inhibitors with drug resistant antiviral activity. Seasonal influenza ... Additionally, we will investigate whether sequence variations in M2 impact drug efficacy. This work will benefit our industrial ...
Genotyping assays detect drug-resistance mutations that are present in the relevant viral genes (i.e., reverse transcriptase ... for by different antiretroviral drugs and of the potential for cross-resistance to other drugs conferred by certain mutations.¶ ... see Drug-Resistance Testing). Viral resistance to antiretroviral drugs can be a key reason for treatment failure. Genetically ... Drug-Resistance Testing Testing for HIV resistance to antiretroviral drugs is a useful tool for guiding antiretroviral therapy ...
... whereas the novel recombinant phenotypic assay is better able to define the level of drug resistance of the single viral ... whereas the novel recombinant phenotypic assay could more precisely detect the level of drug resistance of the single viral ... However, some discrepant results were observed, in that higher drug-resistance levels were detected by the conventional isolate ... recombinant HIV-1 drug-susceptibility assay was developed to evaluate resistance to RT inhibitors. ...
Point mutation in virus that confers drug resistance to NNTRIs.. -Etravirine 35 ... Emtricitabine(FTC)-TPs are incorporated into the viral DNA by viral DNA polymerase and then - terminate viral DNA synthesis ... K103N mutation - associate with what?. What is the one drug exception that can be used? ... Three main viral processes that are targeted by the drug combos used in INITIAL therapy. ...
Selection and characterization of mutations conferring resistance to a HCV RNA dependent RNA polymerase inhibitor A-848837 in ... Mercks New HCV Polymerase Inhibitor Drug Reduces HCV Viral Load by 5.7 Log in 7 Days in Chimps - (06/14/06). ... resistance at 282 is associated with polymerase drug resistance, but PSI-6130 may remain active when mutation is present - (06/ ... Initial Virologic Failure with HIV Drug Resistance and Impact of Resistance on Disease Progression and Death for Patients ...
... and mutations in the gene coding for ExoN can increase viral resistance to remdesivir [13]. However, the mutations so far ... encountered appear to confer a survival disadvantage on the virus.. Remdesivir has been tested in 18 rhesus monkeys infected ... Viral PCR confirmed SARS-CoV-2 infection. The chest X-ray was clear 7 days after the start of the illness, but in view of fears ... The active drug has a half-life in monocytes of approximately 14 hours [11]. The half-maximal effective concentration for ...
A combination of the two newest drugs approved for hepatitis C virus suggests that a strength of one overcomes a weakness of ... But importantly, a viral mutation -- Q80K, which has been shown to confer resistance to the HCV protease inhibitors, had no ... Two HCV Drugs Stronger Than One. by Michael Smith, North American Correspondent, MedPage Today April 15, 2014 ... But the two drugs -- approved at much the same time in 2013 -- were not indicated for use with each other. Physicians and ...
  • In the β-coronavirus murine hepatitis virus (MHV) model, the exonuclease provides the coronavirus some protection, as mutants that lack it are more susceptible to remdesivir, and mutations in the gene coding for ExoN can increase viral resistance to remdesivir [ 13 ]. (cebm.net)
  • LONDON -- A combination of the two newest drugs approved for hepatitis C virus (HCV) suggests that a strength of one overcomes a weakness of the other, a researcher reported. (medpagetoday.com)
  • This phase II study demonstrated very high viral cure rates when a combination of sofusbuvir and simeprevir was used in patients with genotype 1 hepatitis C virus. (medpagetoday.com)
  • Elevated hepatic transaminases, hepatitis, and pancreatitis have been reported, but these have occurred in association with other drugs known to cause these toxicities. (who.int)
  • USFDA approved package labeling for emtricitabine carries a warning that safety and efficacy have not been established for patients co-infected with HIV and HBV and that severe, acute exacerbations of Hepatitis B have been reported in patients following discontinuation of the drug. (who.int)
  • This paper reviews HCV resistance mechanisms, the traditional treatment with and the new standard of care for hepatitis C treatment. (hindawi.com)
  • HCV, like hepatitis B virus (HBV) and HIV, is prone to develop resistance to antiviral drugs. (hindawi.com)
  • There are many that are not discussed here, such as enteroviruses, HIV, hepatitis, and parvovirus, which are discussed in other chapters and essentially every organ system in the body can be impacted by viral infections. (neurologyadvisor.com)
  • Journal of Viral Hepatitis 2002. (powershow.com)
  • Future research in hepatitis B will focus on the best ways to use existing therapies, including telbivudine, sequentially or in combination in order to maximize viral suppression and minimize the development of antiviral resistance. (dovepress.com)
  • Multiple mutations in hepatitis C virus NS5A domain II are required to confer a significant level of resistance to alisporivir. (nih.gov)
  • Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. (kstudy.com)
  • Partial sequencing of the NA and hemagglutinin (HA) genes was performed to confirm the NA H274Y resistance mutation and to determine genetic drift in HA from the A/Brisbane/59/2007 virus recommended for the Northern Hemisphere 2007-08 vaccine. (cdc.gov)
  • Here we assessed the role of fitness-cost and the genetic background for resistance in a real-world epidemiological setting by studying the persistence behavior of transmitted antiretroviral resistance mutations of HIV. (prolekare.cz)
  • This persistence behavior was associated with the predicted fitness cost of a given resistance mutation in the particular genetic background in which it occurred. (prolekare.cz)
  • We found that persistence behavior varied strongly across both mutation types and genetic backgrounds and that persistence was significantly associated with predicted fitness costs. (prolekare.cz)
  • In particular we found that even mutations of the same type tended to persist longer if they occurred in a genetic background where they caused weak fitness costs. (prolekare.cz)
  • Overall our results underline the variability of persistence behavior as well as the important role of fitness costs and the genetic background in the evolution of antimicrobial resistance. (prolekare.cz)
  • Resistance, particularly to drug with low genetic barriers (M184V resistance for 3TC, and K103N resistance for efavirenz) has developed during STIs. (natap.org)
  • The I50L substitution, with or without an A71V substitution, conferred ATV resistance in recombinant viral clones in a variety of genetic backgrounds. (natap.org)
  • Special tests include antiretroviral resistance testing by genotype or phenotype, genetic testing for HLA-B*5701 (associated with abacavir hypersensitivity), and viral tropism testing (ie, CCR5) for maraviroc. (medscape.com)
  • For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. (deepdyve.com)
  • For example, based on gene alterations, it would be not unreasonable for a cancer treatment regimen to require six or more drugs (each targeting a particular genetic alteration), and when one considers the multiple possible dosing regimens, the number of potential combinations rapidly multiplies, achieving numbers as high as 1011 . (deepdyve.com)
  • Some studies have reported decreases in acquired drug resistance in high-income countries, [ 6 , 7 ] which may reflect increased use of drugs with high genetic barriers for resistance and increased use of HIV genotyping and viral load monitoring to guide treatment. (medscape.com)
  • This has led to speculation that DTG might have a higher genetic barrier for the development of drug resistance than the other compounds that are used in therapy. (biomedcentral.com)
  • This turnover drives both the pathogenic process and (even more than mutation rate) the development of genetic variation. (sciencemag.org)
  • No evidence of re-assortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence was observed. (scielo.org.ar)
  • Alagille syndrome is a rare genetic disorder that is caused by hereditary or spontaneous mutations in JAG1 or NOTCH2 on chromosome 20. (medindia.net)
  • Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs. (kstudy.com)
  • The findings from the EMERALD study bring us one step closer to being able to offer those who live with HIV and struggle with adherence an option that combines the efficacy and high genetic barrier to resistance of darunavir with the demonstrated safety profile of tenofovir alafenamide into a single tablet," Eron said in a Janssen press release . (nhivna.org)
  • This is NOT an exhaustive discussion on the outcomes data pertaining to the efficacy and durability of anti-virals! (powershow.com)
  • However, due to the similarities between the two drugs, emtricitabine will not likely be effective in individuals who display antimicrobial resistance to lamivudine. (who.int)
  • Moreover, the use of lamivudine, which is already used in first-line treatment, could avoid the switch to another class of drugs, which could be prescribed later if necessary. (eurekalert.org)
  • Patients with HBV DNA above 900 IU/mL were infected with subgenotypes A1 (n = 3) and D2 (n = 1), and exhibited viral mutations associated with total resistance to lamivudine and partial resistance to entecavir. (bvsalud.org)
  • The two-drug antiretroviral combination dolutegravir and lamivudine is virologically effective and safe in people starting HIV therapy for the first time, according to US research published in the online edition of Clinical Infectious Diseases . (bhiva.org)
  • The two-drug regimen of dolutegravir and lamivudine was generally safe and well-tolerated consistent with the known favorable toxicity profiles of these two agents," comment the authors. (bhiva.org)
  • The week 24 results of the…study showed that the two-drug antiretroviral regimen of dolutegravir and lamivudine was virologically potent and generally safe and well-tolerated in individuals with pre-treatment HIV-1 RNA up to 500,000 copies/ml," conclude the researchers. (bhiva.org)
  • This resistance was primarily due to an H275Y mutation - where a single amino acid substitution ( histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 275 ( Note: some scientists use 'N2 numbering' ( H274Y ) ). (flutrackers.com)
  • After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. (biomedcentral.com)
  • If the patient's viral load (the amount of HIV in the blood) rebounds after being suppressed by ARVs, the virus has likely developed resistance to the ARVs. (wikipedia.org)
  • 1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. (microsoft.com)
  • Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. (cdc.gov)
  • Of the 92 sexually active youths, 39 (or 42%) had at least one plasma viral load measurement of at least 5,000 copies per milliliter after sexual debut. (medpagetoday.com)
  • A patient is starting or changing ART regimen late in pregnancy, in which case an INSTI might be selected because of its ability to rapidly decrease viral load. (nih.gov)
  • The study's 265 patients(2) had an initial viral load below 200 copies/mL, and were followed up for 96 weeks. (eurekalert.org)
  • The rate of treatment failure, defined as a viral load above 500 copies/mL, was 3% (4/132 patients) for dual therapy and 24.8% for monotherapy (33/133 patients). (eurekalert.org)
  • Further several studies showed that viral load rebounds were not significantly different after STIs, suggesting a lack of improved immune control. (natap.org)
  • She had a CD4+ count of 42 cells/mm3 and a viral load of 600,000 copies/mL prior to beginning her most recent regimen. (prn.org)
  • These data supplement previously reported findings, where 83% of patients achieved a ≥ 0.5 log 10 decrease in viral load from baseline seven days after the single loading dose of 2000 mg of ibalizumab (primary endpoint) and a mean reduction in viral load of 1.6 log 10 over the 24 week treatment period with more than 48% of patients experiencing a viral load reduction of more than 2.0 log 10 . (ariva.de)
  • Patients enrolled in this Phase III trial experienced a significant decrease in viral load after receiving a single loading dose of ibalizumab 2,000 mg intravenously (IV) in addition to their failing ART (or no therapy). (ariva.de)
  • Viral load decreases were maintained during the 24-week trial. (ariva.de)
  • 50 copies/mL) was 43% (mean viral load reduction of 3.1 log 10 ) and 50% of patients had a viral load lower than 200 copies/mL. (ariva.de)
  • Patients had a mean HIV-1 viral load of 100,287 copies/mL, with 18% having viral loads above 100,000 copies/mL. (ariva.de)
  • While the earliest antiretroviral agents were developed before many HIV diagnostics were available in the clinic, the development of laboratory tests to measure viral load and CD4+ cell count greatly accelerated progress in drug development. (nih.gov)
  • Viral load assays were able to quantify the levels of HIV RNA in the blood. (caltech.edu)
  • By quantifying the viral load, one now had a faster, more direct way to test antiretroviral regimen efficacy. (caltech.edu)
  • This section first addresses viral genotype and the correlates of viral load and disease progression. (caltech.edu)
  • To be included in the study, patients were required to have an HIV RNA viral load greater than 1,000 copies/mL and to be currently on antiretroviral therapy or on a treatment interruption of less than a month. (thebodypro.com)
  • Children were included if a HIV-1 RNA plasma viral load (VL) result was available for the preceding 12 months. (biomedcentral.com)
  • Viral load and CD4+ T cell testing should ideally be performed twice before initiating or changing an antiretroviral treatment regimen. (cdc.gov)
  • One reason is that current Human Immunodeficiency Virus (HIV) therapies reduce viral load during treatment but titers rebound after treatment is discontinued, which is one of the consequences of virus latency. (justia.com)
  • Current recommendations suggest that antiretroviral therapy be considered in any patient with a viral load higher than 5,000 to 20,000 copies per mL, regardless of the CD4 + count. (aafp.org)
  • Viral load, a measure of the plasma HIV RNA concentration, correlates both with changes in the CD4 + count and with prognosis. (aafp.org)
  • 11 , 12 This comes as an addition to previous recommendations to institute therapy in symptomatic patients and in patients with CD4 + counts of less than 500 per mm 3 (500 × 10 6 per L). Effective combination therapy should decrease a patient's viral load by at least 1 log (10-fold) after three to four weeks of treatment. (aafp.org)
  • They therefore designed a pilot, phase 2, open-label study (ACTG A5353) involving adults with a viral load between 1000 and 500,000 copies/ml who were starting antiretroviral therapy for the first time. (bhiva.org)
  • Viral load was measured at regular intervals over 24 weeks. (bhiva.org)
  • Virological failure was defined as a viral load above 400 copies at weeks 16/20 or above 200 copies/ml at week 24. (bhiva.org)
  • Median baseline viral load and CD4 cell count were 40,000 copies/ml and 387 cells/mm 3 , respectively. (bhiva.org)
  • At baseline, they had a viral load below 50 copies/ml for at least two months. (nhivna.org)
  • In a previous study of acute leukemia, we have shown that WT1 gene mutations occur in both myeloid and biphenotypic subtypes, where they are associated with refractoriness to standard induction chemotherapy. (bloodjournal.org)
  • In contrast to the findings in Wilms' tumor, where mutations in the WT1 gene usually behave according to Knudson's two hit model for tumor suppressor genes, seven of eight leukemia-associated WT1 mutations are heterozygous, implying a dominant or dominant-negative mode of action in hematopoietic cells. (bloodjournal.org)
  • Another approved and marketed class of HIV-1 antiviral therapeutics inhibits the HIV-1 protease, a viral enzyme required to process newly synthesized viral polyproteins into the mature viral gene products, enabling the virus to assemble itself into new infectious virus particles [ 3 ]. (hindawi.com)
  • This drug resistance arises from mutations in the viral protease gene to compromise the protease-PI interaction to facilitate the binding to protease substrate (i.e. (biomedcentral.com)
  • artificial intelligence, drug combination, combination therapy, machine learning, genomic profile Introduction It is becoming increasingly clear that targeted combination therapy is the treatment of choice in many complex human diseases, particularly those resulting from biological dysfunction driven by alterations/mutations in several genes or/and gene networks as is usually the case in cancer . (deepdyve.com)
  • Christianson syndrome is a condition that occurs due to mutations (abnormal changes) in the gene SLC9A6 that is present on X chromosome. (medindia.net)
  • Cloning analysis of the IN gene showed an independent selection of the mutations at loci 155 and 143. (semanticscholar.org)
  • In a recent study of 85 PI-experienced subjects with viral loads between 1,000 and 100,000 copies/mL, lipid levels remained stable -- and some even decreased -- by week 48 in those taking atazanavir (400 mg or 600 mg) and saquinavir (Fortovase) plus two NRTIs , compared with those taking ritonavir, saquinavir, and two NRTIs. (thebody.com)
  • We are continuing to investigate the mechanisms of resistance to nucleoside analogs (NRTIs), and we are also interested in elucidating the mechanism of action of compounds that do not cause an immediate or complete block to DNA synthesis. (cancer.gov)
  • The development of AZT and other NRTIs showed that treating HIV was possible, and these drugs paved the way for discovery and development of new generations of antiretroviral drugs. (nih.gov)
  • Of critical importance for the evaluation of new NRTIs are recent studies showing that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key determinant in the emergence of one or the other resistance pathway. (eurekaselect.com)
  • Collectively, we demonstrate that R292K, E119V, and I222K reduced the inhibitory activity of oseltamivir, not only in the NI assay, but also in infected ferrets, judged particularly by viral loads in nasal washes, and may signal the need for alternative therapeutics. (sigmaaldrich.com)
  • In 2004, when this study was conducted, 80.3% of patients followed in French hospitals were receiving antiretroviral therapy and 21.3% were found to have viral loads of more than 1,000 copies/mL. (thebodypro.com)
  • The H274Y mutation was confirmed by sequence analysis of the N1 genes. (cdc.gov)
  • On the other hand, knowledge of specific resistance mechanisms can inform novel therapeutic approaches to counter this phenomenon, just as knowledge of key driver genes has guided the advent of new therapeutics capable of eliciting meaningful (if transient) initial tumor responses in patients with advanced malignancies. (aacrjournals.org)
  • Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. (aacrjournals.org)
  • One adenosine-based compound, GS-441524, inhibits viral RdRp, but requires a rate-limiting phosphorylation step before it can enter cells. (cebm.net)
  • To understand the mechanism by which a His274Tyr mutation gives rise to drug resistance, we studied a series of NA variant proteins containing various substitutions at position 274. (asm.org)
  • This compound suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. (justia.com)
  • This in accordance with in vivo data that suggest that alisporivir is associated with a low potential for development of viral resistance. (nih.gov)
  • Emtricitabine Capsules 200 mg, supplied by Aurobindo Pharma Ltd., Hyderabad 500 072, India, was the subject of an abbreviated new drug application (ANDA) submitted to the U. S. Food and Drug Administration (USFDA) pursuant to section 505(j) of the U. S. Federal Food, Drug, and Cosmetic Act. (who.int)
  • Since emtricitabine also has in vitro activity against HBV, caution is warranted in using this drug in patients coinfected with HBV. (who.int)
  • The S851Y mutant virus exhibited a low level of resistance to dCMP analogues but high-level resistance to dAMP analogues and to 6-[3-hydroxy-2-(phosphonomethoxy)propoxy]-2,4-diaminopyrimidine, which is considered to mimic the purine ring system. (neb.com)