Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Nerve Endings: Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS.Terminal Repeat Sequences: Nucleotide sequences repeated on both the 5' and 3' ends of a sequence under consideration. For example, the hallmarks of a transposon are that it is flanked by inverted repeats on each end and the inverted repeats are flanked by direct repeats. The Delta element of Ty retrotransposons and LTRs (long terminal repeats) are examples of this concept.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.HIV Long Terminal Repeat: Regulatory sequences important for viral replication that are located on each end of the HIV genome. The LTR includes the HIV ENHANCER, promoter, and other sequences. Specific regions in the LTR include the negative regulatory element (NRE), NF-kappa B binding sites , Sp1 binding sites, TATA BOX, and trans-acting responsive element (TAR). The binding of both cellular and viral proteins to these regions regulates HIV transcription.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.DNA Nucleotidylexotransferase: A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. EC Care: Medical and nursing care of patients in the terminal stage of an illness.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Neuromuscular Junction: The synapse between a neuron and a muscle.Computer Terminals: Input/output devices designed to receive data in an environment associated with the job to be performed, and capable of transmitting entries to, and obtaining output from, the system of which it is a part. (Computer Dictionary, 4th ed.)Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.Kinetics: The rate dynamics in chemical or physical systems.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.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.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.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.Motor Neurons: Neurons which activate MUSCLE CELLS.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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Pituitary Gland, Posterior: Neural tissue of the pituitary gland, also known as the neurohypophysis. It consists of the distal AXONS of neurons that produce VASOPRESSIN and OXYTOCIN in the SUPRAOPTIC NUCLEUS and the PARAVENTRICULAR NUCLEUS. These axons travel down through the MEDIAN EMINENCE, the hypothalamic infundibulum of the PITUITARY STALK, to the posterior lobe of the pituitary gland.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Motor Endplate: The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors.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.Carbohydrate Sequence: The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.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).Molecular Weight: The sum of the weight of all the atoms in a molecule.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.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Goldfish: Common name for Carassius auratus, a type of carp (CARPS).Pyridinium CompoundsRecombinant Proteins: Proteins prepared by recombinant DNA technology.Nerve Tissue Proteinsgamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Complement Membrane Attack Complex: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.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.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.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.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.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.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Genes, Viral: The functional hereditary units of VIRUSES.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.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.Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Synapsins: A family of synaptic vesicle-associated proteins involved in the short-term regulation of NEUROTRANSMITTER release. Synapsin I, the predominant member of this family, links SYNAPTIC VESICLES to ACTIN FILAMENTS in the presynaptic nerve terminal. These interactions are modulated by the reversible PHOSPHORYLATION of synapsin I through various signal transduction pathways. The protein is also a substrate for cAMP- and CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. It is believed that these functional properties are also shared by synapsin II.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.DNA Nucleotidyltransferases: Enzymes that catalyze the incorporation of deoxyribonucleotides into a chain of DNA. EC 2.7.7.-.Retroelements: Elements that are transcribed into RNA, reverse-transcribed into DNA and then inserted into a new site in the genome. Long terminal repeats (LTRs) similar to those from retroviruses are contained in retrotransposons and retrovirus-like elements. Retroposons, such as LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS do not contain LTRs.Oligosaccharides: Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form.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.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Vesicular Glutamate Transport Protein 2: A vesicular glutamate transporter protein that is predominately expressed in the DIENCEPHALON and lower brainstem regions of the CENTRAL NERVOUS SYSTEM.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.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.Synaptic Membranes: Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters.Mice, Inbred C57BLMuscles: Contractile tissue that produces movement in animals.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.Rana pipiens: A highly variable species of the family Ranidae in Canada, the United States and Central America. It is the most widely used Anuran in biomedical research.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Vesicular Glutamate Transport Protein 1: A vesicular glutamate transporter protein that is predominately expressed in TELENCEPHALON of the BRAIN.Carbohydrate Conformation: The characteristic 3-dimensional shape of a carbohydrate.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Animals, Newborn: Refers to animals in the period of time just after birth.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Synaptophysin: A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Alkynes: Hydrocarbons with at least one triple bond in the linear portion, of the general formula Cn-H2n-2.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Retinal Bipolar Cells: INTERNEURONS of the vertebrate RETINA containing two processes. They receive inputs from the RETINAL PHOTORECEPTOR CELLS and send outputs to the RETINAL GANGLION CELLS. The bipolar cells also make lateral connections in the retina with the RETINAL HORIZONTAL CELLS and with the AMACRINE CELLS.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)DNA Restriction Enzymes: Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Retroviridae: Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Viral Proteins: Proteins found in any species of virus.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.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.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Astacoidea: A superfamily of various freshwater CRUSTACEA, in the infraorder Astacidea, comprising the crayfish. Common genera include Astacus and Procambarus. Crayfish resemble lobsters, but are usually much smaller.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Terminally Ill: Persons with an incurable or irreversible illness at the end stage that will result in death within a short time. (From O'Leary et al., Lexikon: Dictionary of Health Care Terms, Organizations, and Acronyms for the Era of Reform, 1994, p780)Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Afferent Pathways: Nerve structures through which impulses are conducted from a peripheral part toward a nerve center.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).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.Receptors, Presynaptic: Neurotransmitter receptors located on or near presynaptic terminals or varicosities. Presynaptic receptors which bind transmitter molecules released by the terminal itself are termed AUTORECEPTORS.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Protein PrecursorsDopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Nerve Fibers: Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Axonal Transport: The directed transport of ORGANELLES and molecules along nerve cell AXONS. Transport can be anterograde (from the cell body) or retrograde (toward the cell body). (Alberts et al., Molecular Biology of the Cell, 3d ed, pG3)Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Mammary Tumor Virus, Mouse: The type species of BETARETROVIRUS commonly latent in mice. It causes mammary adenocarcinoma in a genetically susceptible strain of mice when the appropriate hormonal influences operate.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Neurosecretion: The production and release of substances such as NEUROTRANSMITTERS or HORMONES from nerve cells.Histocytochemistry: Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.DNA, Recombinant: Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.Epidermis: The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.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.PolysaccharidesAcetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Gene Products, tat: Trans-acting transcription factors produced by retroviruses such as HIV. They are nuclear proteins whose expression is required for viral replication. The tat protein stimulates LONG TERMINAL REPEAT-driven RNA synthesis for both viral regulatory and viral structural proteins. tat stands for trans-activation of transcription.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Lectins: Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.Proviruses: Duplex DNA sequences in eukaryotic chromosomes, corresponding to the genome of a virus, that are transmitted from one cell generation to the next without causing lysis of the host. Proviruses are often associated with neoplastic cell transformation and are key features of retrovirus biology.tat Gene Products, Human Immunodeficiency Virus: Proteins encoded by the TAT GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Quaternary Ammonium Compounds: Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.Evoked Potentials: Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.N-Acetylneuraminic Acid: An N-acyl derivative of neuraminic acid. N-acetylneuraminic acid occurs in many polysaccharides, glycoproteins, and glycolipids in animals and bacteria. (From Dorland, 28th ed, p1518)Carbohydrates: The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n.Neuronal Plasticity: The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Chromosome Deletion: Actual loss of portion of a chromosome.Brain Stem: The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA.Colubridae: The largest family of snakes, comprising five subfamilies: Colubrinae, Natricinae, Homalopsinae, Lycodontinae, and Xenodontinae. They show a great diversity of eating habits, some eating almost anything, others having a specialized diet. They can be oviparous, ovoviviparous, or viviparous. The majority of North American snakes are colubrines. Among the colubrids are king snakes, water moccasins, water snakes, and garter snakes. Some genera are poisonous. (Goin, Goin, and Zug, Introduction to Herpetology, 3d ed, pp321-29)

Slippery slopes in flat countries--a response. (1/1175)

In response to the paper by Keown and Jochemsen in which the latest empirical data concerning euthanasia and other end-of-life decisions in the Netherlands is discussed, this paper discusses three points. The use of euthanasia in cases in which palliative care was a viable alternative may be taken as proof of a slippery slope. However, it could also be interpreted as an indication of a shift towards more autonomy-based end-of-life decisions. The cases of non-voluntary euthanasia are a serious problem in the Netherlands and they are only rarely justifiable. However, they do not prove the existence of a slippery slope. Persuading the physician to bring euthanasia cases to the knowledge of the authorities is a problem of any euthanasia policy. The Dutch notification procedure has recently been changed to reduce the underreporting of cases. However, many questions remain.  (+info)

Conditions required for a law on active voluntary euthanasia: a survey of nurses' opinions in the Australian Capital Territory. (2/1175)

OBJECTIVES: To ascertain which conditions nurses believe should be in a law allowing active voluntary euthanasia (AVE). DESIGN: Survey questionnaire posted to registered nurses (RNs). SETTING: Australian Capital Territory (ACT) at the end of 1996, when active voluntary euthanasia was legal in the Northern Territory. SURVEY SAMPLE: A random sample of 2,000 RNs, representing 54 per cent of the RN population in the ACT. MAIN MEASURES: Two methods were used to look at nurses' opinions. The first involved four vignettes which varied in terms of critical characteristics of each patient who was requesting help to die. The respondents were asked if the law should be changed to allow any of these requests. There was also a checklist of conditions, most of which have commonly been included in Australian proposed laws on AVE. The respondents chose those which they believed should apply in a law on AVE. RESULTS: The response rate was 61%. Support for a change in the law to allow AVE was 38% for a young man with AIDS, 39% for an elderly man with early stage Alzheimer's disease, 44% for a young woman who had become quadriplegic and 71% for a middle-aged woman with metastases from breast cancer. The conditions most strongly supported in any future AVE law were: "second doctor's opinion", "cooling off period", "unbearable protracted suffering", "patient fully informed about illness and treatment" and "terminally ill". There was only minority support for "not suffering from treatable depression", "administer the fatal dose themselves" and "over a certain age". CONCLUSION: Given the lack of support for some conditions included in proposed AVE laws, there needs to be further debate about the conditions required in any future AVE bills.  (+info)

Use of resources and costs of palliative care with parenteral fluids and analgesics in the home setting for patients with end-stage cancer. (3/1175)

BACKGROUND: In 1992 a home care technology project was started in which infusion therapy in the home setting was made available for patients with end-stage cancer. Beside aspects of feasibility and quality of life the resource utilization and costs of this transition was studied. PATIENTS AND METHODS: We conducted a cost evaluation study, to determine the actual cost of managing patients with endstage cancer who require parenteral administration of fluid or analgesics in the home setting. A total of 128 patients were prospectively followed, with a detailed analysis of some aspects in a sample of 24 patients. RESULTS: The cost for each patient was found to be between $250.00 and $300.00 per day, half of which are for hospital charges, even with this active home care technology program. One-third of the costs can be attributed to primary health care activities, in particular those of the district nurses. A hypothetical control group (n = 25) was constructed based on current practice and chart review. Patients in this group would have cost around $750.00 per day. With a median treatment period of 16 days this means a saving of $8000.00 per patient. CONCLUSION: Our data suggest that significant savings can be obtained by implementing programs transferring palliative care technology to the home setting.  (+info)

The timing of do-not-resuscitate orders and hospital costs. (4/1175)

The relation between the timing of do-not-resuscitate (DNR) orders and the cost of medical care is not well understood. This prospective observational study compares hospital costs and length of stay of 265 terminally ill patients with admission DNR orders, delayed DNR orders (occurring after 24 hours), or no DNR orders (full code). Patients whose orders remained full code throughout a hospital stay had similar lengths of stay, total hospital costs, and daily costs as patients with admission DNR orders. Patients with delayed DNR orders, by contrast, had a greater mortality, longer length of stay, and higher total costs than full code or admission DNR patients, but similar daily costs. The causes of delay in DNR orders and the associated higher costs are a matter for future research.  (+info)

Do social factors affect where patients die: an analysis of 10 years of cancer deaths in England. (5/1175)

BACKGROUND: This study investigated whether indices of social deprivation were related to the proportion of cancer patients who died at home. METHODS: Data were derived from death registrations for all cancer deaths 1985-1994 in England. Two indices of deprivation (Underprivileged Area Score (UPA), or Jarman, and Townsend scores) were calculated for each electoral ward; 1991 Census data were used. The scores use combinations of variables, including the percentage in overcrowded homes, the percentage of elderly people living alone, the percentage of one-parent families, etc. A high score indicates more deprivation. The main outcome measures were the proportion (in five and ten year averages) of cancer deaths which occurred at home, calculated for every electoral ward (with populations usually ranging from 5000 to 11,000). Spearman rho was used to test for correlations between the proportion of cancer deaths at home and deprivation score. Electoral wards were categorized by deprivation score into three groups of equal size and analysed over 10 years. Multivariate analysis was used to determine the relative association of different patient based and electoral ward variables with cancer death at home. p < 0.05 (two-tailed) was taken as significant. RESULTS: There were over 1.3 million death registrations from cancer in the 10 years. The proportion who died at home was 0.27, in hospital 0.47, and other setting 0.26. There were wide variations (0.05-0.75) in the proportion of people who died at home in different electoral wards. Small inverse correlations were found between the percentage who died at home and the UPA (-0.35; p < 0.001) and Townsend (-0.26; p < 0.001) scores. The correlations were greatest in North Thames (-0.63, UPA) and smallest in West Midlands (-0.20, UPA). The proportion of home deaths for the different bands of deprivation were: 0.30 (low deprivation), 0.27 (middle deprivation) and 0.24 (high deprivation). Plotting the trends over 10 years suggests no change in this relationship. Multiple regression analysis predicted several ward and patient characteristics and accounted for 30 per cent of the variation. Increased age (patient variable), Jarman score and ethnic minorities (both ward variables) were associated with fewer patients dying at home. Being male and having cancer of the digestive organs were associated with home death. CONCLUSION: There are wide variations in the percentage of cancer deaths at home in different electoral wards. Social factors are inversely correlated with home cancer death, and may explain part of this variation. Home care in deprived areas may be especially difficult to achieve.  (+info)

Abandonment of terminally ill patients in the Byzantine era. An ancient tradition? (6/1175)

Our research on the texts of the Byzantine historians and chroniclers revealed an apparently curious phenomenon, namely, the abandonment of terminally ill emperors by their physicians when the latter realised that they could not offer any further treatment. This attitude tallies with the mentality of the ancient Greek physicians, who even in Hippocratic times thought the treatment and care of the terminally ill to be a challenge to nature and hubris to the gods. Nevertheless, it is a very curious attitude in the light of the concepts of the Christian Byzantine physicians who, according to the doctrines of the Christian religion, should have been imbued with the spirit of philanthropy and love for their fellowmen. The meticulous analysis of three examples of abandonment of Byzantine emperors, and especially that of Alexius I Comnenus, by their physicians reveals that this custom, following ancient pagan ethics, in those times took on a ritualised form without any significant or real content.  (+info)

The status of the do-not-resuscitate order in Chinese clinical trial patients in a cancer centre. (7/1175)

OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom.  (+info)

Edmonton Regional Palliative Care Program: impact on patterns of terminal cancer care. (8/1175)

The Edmonton Regional Palliative Care Program was established in July 1995 to measure the access of patients with terminal cancer to palliative care services, decrease the number of cancer-related deaths in acute care facilities and increase the participation of family physicians in the care of terminally ill patients. In this retrospective study the authors compared the pattern of care and site of deaths before establishment of the program (1992/93) and during its second year of operation (1996/97). Significantly more cancer-related deaths occurred in acute care facilities in 1992/93 than in 1996/97 (86% [1119/1304] v. 49% [633/1279]) (p < or = 0.001). The number of inpatient days decreased, from 24,566 in 1992/93 to 6960 in 1996/97. More cancer patients saw a palliative care consult team in 1996/97 than in 1992/93 (82% v. 22%). The shift from deaths in acute care facilities to palliative hospices suggests that the establishment of an integrated palliative care program has increased access of patients with terminal cancer to palliative care.  (+info)

  • This section summarizes the information that will allow oncology clinicians and patients with advanced cancer to create a plan of care to improve QOL at the end of life (EOL) by making informed choices about the potential harms of continued aggressive treatment and the potential benefits of palliative or hospice care. (
  • The study associates this reduced access and consequent diminished use of hospice services with a reduced quality of end-of-life care for these patients. (
  • Building on previous research that correlated a longer duration of hospice care with increased quality of end-of-life care, this study analyzed additional factors that have been associated with poorer end-of-life care. (
  • Researchers found that, compared with leukemia patients who did not enroll in hospice care, those who did were far less likely to die in the hospital (3 percent vs 75 percent) or receive chemotherapy during the last two weeks of life (5 percent vs 16 percent). (
  • Additionally, they found that patients who needed periodic blood transfusions spent about half as much time in hospice care compared with leukemia patients who were not reliant on these transfusions. (
  • We found a significant association between transfusion dependence and less meaningful use of hospice care at the end of life among patients with leukemia," said Thomas W. LeBlanc, MD, associate professor of medicine at Duke Cancer Institute in Durham, NC, and senior author of the study. (
  • Transfusion-dependent patients were significantly more likely to spend fewer than three days in hospice care (27 percent) compared with patients who were not transfusion-dependent (19 percent), he said, associating longer time spent in hospice care with more meaningful use of the service. (
  • According to Dr. LeBlanc, one of the barriers to the use of hospice care by transfusion-dependent patients with advanced leukemia is that many clinicians consider blood transfusions to be disease-modifying therapy rather than comfort care, as transfusions can help some patients to live longer and feel better. (
  • Another is that, under Medicare's reimbursement protocol, the cost of blood transfusions is not compensated separately, but must be covered within the per-diem rate paid for hospice care, reducing the ability of hospice agencies to provide transfusion support as part of their services. (
  • Furthermore, the logistical complexities of blood transfusion also often preclude providing the service in patients' homes, where most hospice patients receive care. (
  • Patients were considered transfusion-dependent if, within 30 days before death or enrollment in hospice care, they received two or more blood transfusions at least five days apart. (
  • Results showed that from 2001-2011, slightly more transfusion-dependent patients enrolled in hospice care than patients who were not transfusion-dependent (47 versus 43 percent), but that their median length of stay in hospice care was significantly shorter than those who were not transfusion-dependent (6 versus 11 days). (
  • This suggests that clinicians tend to enroll patients in hospice during the very last few days of life, but we know from other studies that the earlier patients enter hospice care, the more likely they are to obtain the full benefit of what hospice can offer in terms of an improved quality of life," said Dr. Olszewski, lead study author. (
  • 1 ] Anticipating the end of life (EOL) and making health care decisions about appropriate or preferred treatment or care near the EOL is intellectually challenging and emotionally distressing for patients with advanced cancer, their families and friends, oncology clinicians, and other professional caregivers. (
  • Utilization of burdensome and expensive health care resources of little therapeutic benefit. (
  • The purpose of this summary is to review the evidence surrounding conversations about EOL care in advanced cancer to inform providers, patients, and families about the transition to compassionate and effective EOL care. (
  • Oncology clinicians are obligated to explore, with the patient and family, the potential impact of continued disease-directed treatments or care directed at the patient's symptoms and QOL. (
  • In addition, information about outcomes associated with cardiopulmonary resuscitation (CPR) and admission to the intensive care unit (ICU) at the EOL will allow the oncology clinician to better present options to patients with advanced cancer who are near the EOL. (
  • Atlanta, Dec. 11, 2017) -- For patients with advanced leukemia, access to high-quality end-of-life care appears to be reduced in those dependent on blood transfusions, according to a new study being presented during the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta. (
  • These findings suggest that patients are having to choose between getting the transfusions they need and getting high-quality end-of-life care," Dr. LeBlanc said. (
  • Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. (
  • Objective: To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. (
  • Objectives The purpose of this study was to determine the effect of amino-terminal pro-brain natriuretic peptide (N-BNP) on the diagnostic accuracy of heart failure (HF) in primary care. (
  • Amino-terminal pro-brain natriuretic peptide is present in high levels in cardiac dysfunction and may improve the diagnostic accuracy of HF in primary care. (
  • In the past 15 years, palliative care has emerged from near obscurity to become a board-certified medical specialty for physicians and a prominent part of contemporary healthcare for all providers and their patients. (
  • Professional competence and development of specific skills for healthcare providers who are involved in palliative care, especially the ability to communicate compassionately and effectively in order to help patients and/or family members make decisions about their care by determining treatment goals, developing appropriate strategies in line with those goals and preparing advance directives. (
  • This is a challenge for all of us, but doctors and healthcare professionals could also benefit from training and a greater understanding of the work that hospices do and what is available from palliative care. (
  • In the age of rising healthcare costs, some have questioned whether the primary benefits of palliative care can also translate into collateral reductions in healthcare use and its associated costs. (
  • There is therefore an urgent need for high-quality studies that evaluate the ability of palliative care to relieve the high burden of suffering and healthcare use in patients with noncancer illness who have a very different trajectory of dying. (
  • We were surprised to find an increased rate of healthcare use associated with palliative care in those dying from dementia, a finding that will require further study to explain. (
  • Lack of awareness of the availability of palliative care or its benefits was not the fault of these patients or their healthcare providers. (
  • But when I referred these patients to our palliative care teams who were well equipped to provide care for them at home and prevent unwanted transfers to the emergency department, I wondered, if palliative care can do it here, can they do it across an entire healthcare system? (
  • As the evidence base for the benefits of palliative care expands, the next challenge facing healthcare systems is how to organize and disseminate sustainable care that aligns with the individual preferences of our patients, a goal set by the Institute for Healthcare Improvement in the United States. (
  • To meet these enormous challenges, we need sustained investment in healthcare provider training and the scaling of existing effective models of collaborative palliative care, as well as research to evaluate its effectiveness. (
  • Whatever your healthcare needs, our staff is here to welcome you and help ensure you receive the care you need to reach your optimum level of health and well-being. (
  • Be sure to alert your healthcare provider about the wound so they can develop a plan to care for it properly. (
  • It is the first palliative care service in the private healthcare sector with full-time specialists in palliative medicine. (
  • I believe it is high time the NMA begins to have an open mind as to how we can run the healthcare system in Nigeria in order to make it a patient-centered care. (
  • “In 2017, healthcare professionals across the globe are more concerned about working together to deliver patient-centered care. (
  • Efuribe, who is a healthcare promotion ambassador on self care, wellness and better healthcare, said to build an efficient health service delivery system, all healthcare workers’ salaries should be revised and harmonised so that people can be rewarded as well as gain some fulfillment for the services they offer, adding that the focus should not be relativity or superiority in my opinion. (
  • The author has drawn on his great experience in both consultation-liaison psychiatry and palliative medicine to produce an essential, evidence-based guide for all healthcare professionals involved in palliative care. (
  • Hall, an 82-year-old former World War II prisoner of war who is serving a life sentence for murder, has spent nearly a decade in the infirmary at Iowa State Penitentiary with a terminal heart ailment. (
  • [email protected] Studying end of life in dementia is challenging because of the frailty of the population, additional cognitive problems and difficulty of assessing when patients enter the terminal phase. (
  • Quantitative studies, including observational studies which are frequently ethically appropriate, are helpful to increase the desired evidence base of effective treatment and Mobile phone end-of-life care in dementia patients. (
  • Pain one's health, the palliative care concern the last period of a man's life, trying to give him back the largest possible self-sufficiency. (
  • This is the first study focused on black/white differences that prospectively asked [terminal cancer patients] what kind of care they wanted at the end of life, and then documented the kind of care they actually received and the place of their death," said Elizabeth Trice, MD, PhD, of Dana-Farber, lead author. (
  • The article has important implications for how we approach and treat advanced dementia in the nursing home and hopefully will spur providers to provide care that reduces and avoids suffering and improves the quality of life of their patients. (
  • He notes, "now some 30 years after my grandmother's death, end-of-life care for dementia does not look all that different from the treatment she received. (
  • Hopefully, recognizing that end stage dementia is a terminal condition will result in improved care---care focused on the quality of life of patients and the needs of their families. (
  • This brochure was created by Improving End-of-Life Care in First Nations Communities Centre for Education and Research on Aging & Health. (
  • It explains what changes to expect when caring for a loved one at the end-of-life. (
  • Palliative care needs to go hand in hand with hospital treatment and should be available for all people with advanced and progressive illnesses and life-shortening conditions. (
  • Sufferers should be able to plan ahead for their end-of-life care and ensure that their wishes are known. (
  • Research has shown that early referral for palliative care can improve the quality of life and lengthen it. (
  • We need to have properly funded nationwide palliative care provision that is integrated with local authorities, community care providers and local NHS providers, so that there is a comprehensive and coherent way of addressing end-of-life care. (
  • There is still a big taboo about talking about end-of-life care and there is limited understanding among the public about what palliative care is and when it is appropriate. (
  • In Japan, only a few hospitals play a role in home medical care including end-of-life care. (
  • Communication and planning for heart failure (HF) care near the end of life is known to be complex. (
  • Overall however, there were positive associations between the number of physician visits and the recognition of the resident's terminal phase and between the number of physician visits and the resident having palliation as main treatment goal in the last week of life. (
  • The End-of-Life Care Research Group aims to conduct high-quality scientific research in end-of-life care in Belgium and Europe. (
  • The research group is spearheaded by a number of experienced researchers and strives to expand expertise in end-of-life care research. (
  • BACKGROUND Efforts to improve communication between physicians and dying patients have been unsuccessful, and guidelines for improving patient-physician communication about end-of-life care are based primarily on expert opinion. (
  • This study assessed which aspects of communication between patients and physicians are important in end-of-life care. (
  • What is wrong with end-of-life care? (
  • At All Caring Hospice, we understand that patients with life-limiting conditions or terminal illnesses have unique experiences. (
  • Support with difficult decisions - Hospice care helps families make difficult decisions and choices that may impact their loved ones health and quality of life. (
  • Many people with a terminal condition, or who have a loved one with a life-limiting illness, have heard of hospice care. (
  • Practicing in the area of hospice, I am often faced with caring for patients at end of life. (
  • You may find the End of Life Care article more useful, or one of our other health articles . (
  • A report from the National End of Life Care Intelligence Network compared people's preferences for place of death with actual place of death in England and reported that variations exist across the country and between conditions (69% of people with non-cancerous respiratory conditions die in hospital) [ 3 ] . (
  • Five "Priorities of Care" are described and form the focus of care at the end of life. (
  • Palliative medicine is the branch of medicine in palliative care, which aims to relieve suffering and improve the quality of life of patients who are facing life-threatening illnesses such as advanced cancers. (
  • No, although terminal care or hospice care (which generally implies the medical care in the last few days or months of life) is an important part in palliative care. (
  • Palliative Care Services may be involved with patients who are still receiving active cancer treatment such as chemotherapy or radiation therapy, and are not necessarily in their last days or months of life. (
  • We provide four main categories of services: Cancer Pain Management, Discharge and Home Care Planning, Advance Care Planning, and End-of-Life Care. (
  • 68-76% of the general population and medical practitioners expressed disapproval of life-extending medical treatment of terminal patients suffering pain. (
  • 5. Most medical practitioners felt that some medical treatments, such as bedsore care, should be continued in lieu of life support, but there were differences in opinion between practitioners at various types of medical facilities regarding the necessity of such specific measures as, for example, blood pressure monitoring by automatic sphygmomanometer among the medical facilities. (
  • CONCLUSION: Both the general population and the medical practitioners in Japan tended to oppose life-extending medical treatment for painful terminal cases and patients in a prolonged vegetable state. (
  • The current legal definition of 'terminal illness' is not in keeping with the definition of 'end of life' and lacks any clinical relevance. (
  • Hospice care is a specific type of palliative care for patients in the last six months of life. (
  • To receive hospice care, adults need to end life-prolonging treatment. (
  • To evaluate, in patients with heart failure, the effect of a self-care promotion program using a multifaceted strategy in comparison to the usual care about acceptability to the application of SMS, patient and / or family satisfaction with care, quality of life scales health scales, self-care scales and knowledge on HF, visual analog scale of dyspnea, and clinical outcomes at 30 and 180 days. (
  • Reuters Health) - A new study adds to evidence that hospice care during the last six months of life is associated with better overall experiences for patients and a lower likelihood of dying in a hospital. (
  • If someone is hospitalized and approaching the end of life, hospice care is more optimal so they can get the care they need," she told Reuters Health by phone. (
  • end-of-life care is available through hospice and palliative care programs, there should be no reason anyone would need to seek PAS" (1). (
  • After years of neglect, care at the end of life is receiving increasing attention and concern. (
  • When the time is right, palliative and hospice care can offer wholistic end of life support and resources. (
  • Services related to end-of-life care prescribed for individuals, generally with 6 months or less to live, that can be provided in the home or in a facility. (
  • It's important to consider long term care and end-of-life care options. (
  • There is no standardized life expectancy for a patient to be considered terminal, although it is generally months or less. (
  • Life expectancy for terminal patients is a rough estimate given by the physician based on previous data and does not always reflect true longevity. (
  • Because terminal patients are aware of their oncoming deaths, they have more time to prepare advance care planning, such as advance directives and living wills, which have been shown to improve end-of-life care. (
  • Palliative care can also help patients make decisions and come to understand what they want regarding their treatment goals and quality of life. (
  • and finally, the expanding expectancies of the population in complex international locations for a finished and delicate carrier for sufferers, kin and care givers on the terminal section of ailment. (
  • It cannot be right that palliative care funding is dependent on local clinical commissioning groups, whose contributions to local hospices' costs range as widely as 1% to 50% from region to region. (
  • This week is Children's Hospice Week, and the Rainbow Trust Children's Charity has identified that hospices save the NHS money by freeing up hospital beds, reducing the number of missed appointments and, in the case of children with terminal illnesses, helping parents stay together by allowing them to manage their feelings better in a supportive environment. (
  • Comments on the Proposed Rule to Amend Various Aspects of Medicare re: Reimbursing Medicare Providers for Advance Care Planning Counseling Sessions Centers for Medicare & Medicaid Services Department of Health and Human Services Room 445-G Hubert H. Humphrey Building 200 Independence Avenue SW Washington, DC 20201 Attn: CMS-1625-P …we respectfully submit the following comments on the Proposed Rule to amend various aspects of the Medicare program. (
  • Revised throughout and greatly expanded by the addition of two entirely new chapters, it reviews the major psychiatric syndromes encountered in palliative care - depression, anxiety, delirium - and examines psychopharmacological and psychological interventions in detail. (
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