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  • Artikel  (72.934)
  • Artikel: DFG Deutsche Nationallizenzen  (72.934)
  • 1995-1999  (54.621)
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  • Medizin  (72.934)
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  • 1
    Digitale Medien
    Digitale Medien
    PROTEINS OF THE ADF/COFILIN FAMILY: Essential Regulators of Actin Dynamics (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 185-230 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Ubiquitous among eukaryotes, the ADF/cofilins are essential proteins responsible for the high turnover rates of actin filaments in vivo. In vertebrates, ADF and cofilin are products of different genes. Both bind to F-actin cooperatively and induce a twist in the actin filament that results in the loss of the phalloidin-binding site. This conformational change may be responsible for the enhancement of the off rate of subunits at the minus end of ADF/cofilin-decorated filaments and for the weak filament-severing activity. Binding of ADF/cofilin is competitive with tropomyosin. Other regulatory mechanisms in animal cells include binding of phosphoinositides, phosphorylation by LIM kinases on a single serine, and changes in pH. Although vertebrate ADF/cofilins contain a nuclear localization sequence, they are usually concentrated in regions containing dynamic actin pools, such as the leading edge of migrating cells and neuronal growth cones. ADF/cofilins are essential for cytokinesis, phagocytosis, fluid phase endocytosis, and other cellular processes dependent upon actin dynamics.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.185
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  • 2
    Digitale Medien
    Digitale Medien
    VERTEBRATE ENDODERM DEVELOPMENT (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 393-410 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Endoderm, one of the three principal germ layers, contributes to all organs of the alimentary tract. For simplicity, this review divides formation of endodermal organs into four fundamental steps: (a) formation of endoderm during gastrulation, (b) morphogenesis of a gut tube from a sheet of cells, (c) budding of organ domains from the tube, and (d) differentiation of organ-specific cell types within the growing buds. We discuss possible mechanisms that regulate how undifferentiated endoderm becomes specified into a myriad of cell types that populate the respiratory and gastrointestinal tracts.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.393
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  • 3
    Digitale Medien
    Digitale Medien
    REGULATION OF NUCLEAR LOCALIZATION: A Key to a Door (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 291-339 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Information can be transferred between the nucleus and the cytoplasm by translocating macromolecules across the nuclear envelope. Communication of extracellular or intracellular changes to the nucleus frequently leads to a transcriptional response that allows cells to survive in a continuously changing environment. Eukaryotic cells have evolved ways to regulate this movement of macromolecules between the cytoplasm and the nucleus such that the transfer of information occurs only under conditions in which a transcriptional response is required. This review focuses on the ways in which cells regulate movement of proteins across the nuclear envelope and the significance of this regulation for controlling diverse biological processes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.291
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  • 4
    Digitale Medien
    Digitale Medien
    INTEGRATION OF SIGNALING NETWORKS THAT REGULATE DICTYOSTELIUM DIFFERENTIATION (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 469-517 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract In Dictyostelium amoebae, cell-type differentiation, spatial patterning, and morphogenesis are controlled by a combination of cell-autonomous mechanisms and intercellular signaling. A chemotactic aggregation of ~105 cells leads to the formation of a multicellular organism. Cell-type differentiation and cell sorting result in a small number of defined cell types organized along an anteroposterior axis. Finally, a mature fruiting body is created by the terminal differentiation of stalk and spore cells. Analysis of the regulatory program demonstrates a role for several molecules, including GSK-3, signal transducers and activators of transcription (STAT) factors, and cAMP-dependent protein kinase (PKA), that control spatial patterning in metazoans. Unexpectedly, two component systems containing histidine kinases and response regulators also play essential roles in controlling Dictyostelium development. This review focuses on the role of cAMP, which functions intracellularly to mediate the activity of PKA, an essential component in aggregation, cell-type specification, and terminal differentiation. Cytoplasmic cAMP levels are controlled through both the regulated activation of adenylyl cyclases and the degradation by a phosphodiesterase containing a two-component system response regulator. Extracellular cAMP regulates G-protein-dependent and -independent pathways to control aggregation as well as the activity of GSK-3 and the transcription factors GBF and STATa during multicellular development. The integration of these pathways with others regulated by the morphogen DIF-1 to control cell fate decisions are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.469
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  • 5
    Digitale Medien
    Digitale Medien
    THE TRANSLOCON: A Dynamic Gateway at the ER Membrane (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 799-842 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Cotranslational protein translocation across and integration into the membrane of the endoplasmic reticulum (ER) occur at sites termed translocons. Translocons are composed of several ER membrane proteins that associate to form an aqueous pore through which secretory proteins and lumenal domains of membrane proteins pass from the cytoplasm to the ER lumen. These sites are not passive holes in the bilayer, but instead are quite dynamic both structurally and functionally. Translocons cycle between ribosome-bound and ribosome-free states, and convert between translocation and integration modes of operation. These changes in functional state are accompanied by structural rearrangements that alter translocon conformation, composition, and interactions with ligands such as the ribosome and BiP. Recent studies have revealed that the translocon is a complex and sophisticated molecular machine that regulates the movement of polypeptides through the bilayer, apparently in both directions as well as laterally into the bilayer, all while maintaining the membrane permeability barrier.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.799
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  • 6
    Digitale Medien
    Digitale Medien
    SYNAPTIC VESICLE BIOGENESIS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 733-798 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Synaptic vesicles, which have been a paradigm for the fusion of a vesicle with its target membrane, also serve as a model for understanding the formation of a vesicle from its donor membrane. Synaptic vesicles, which are formed and recycled at the periphery of the neuron, contain a highly restricted set of neuronal proteins. Insight into the trafficking of synaptic vesicle proteins has come from studying not only neurons but also neuroendocrine cells, which form synaptic-like microvesicles (SLMVs). Formation and recycling of synaptic vesicles/SLMVs takes place from the early endosome and the plasma membrane. The cytoplasmic machinery of synaptic vesicle/SLMV formation and recycling has been studied by a variety of experimental approaches, in particular using cell-free systems. This has revealed distinct machineries for membrane budding and fission. Budding is mediated by clathrin and clathrin adaptors, whereas fission is mediated by dynamin and its interacting protein SH3p4, a lysophosphatidic acid acyl transferase.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.733
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  • 7
    Digitale Medien
    Digitale Medien
    [PSI+]: AN EPIGENETIC MODULATOR OF TRANSLATION TERMINATION EFFICIENCY (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 661-703 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The [PSI+] factor of the yeast Saccharomyces cerevisiae is an epigenetic regulator of translation termination. More than three decades ago, genetic analysis of the transmission of [PSI+] revealed a complex and often contradictory series of observations. However, many of these discrepancies may now be reconciled by a revolutionary hypothesis: protein conformation-based inheritance (the prion hypothesis). This model predicts that a single protein can stably exist in at least two distinct physical states, each associated with a different phenotype. Propagation of one of these traits is achieved by a self-perpetuating change in the protein from one form to the other. Mounting genetic and biochemical evidence suggests that the determinant of [PSI+] is the nuclear encoded Sup35p, a component of the translation termination complex. Here we review the series of experiments supporting the yeast prion hypothesis and provide another look at the 30 years of work preceding this theory in light of our current state of knowledge.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.661
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  • 8
    Digitale Medien
    Digitale Medien
    BLUE-LIGHT PHOTORECEPTORS IN HIGHER PLANTS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 33-62 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract In the past few years great progress has been made in identifying and characterizing plant photoreceptors active in the blue/UV-A regions of the spectrum. These photoreceptors include cryptochrome 1 and cryptochrome 2, which are similar in structure and chromophore composition to the prokaryotic DNA photolyases. However, they have a C-terminal extension that is not present in photolyases and lack photolyase activity. They are involved in regulation of cell elongation and in many other processes, including interfacing with circadian rhythms and activating gene transcription. Animal cryptochromes that play a photoreceptor role in circadian rhythms have also been characterized. Phototropin, the protein product of the NPH1 gene in Arabidopsis, likely serves as the photoreceptor for phototropism and appears to have no other role. A plasma membrane protein, it serves as photoreceptor, kinase, and substrate for light-activated phosphorylation. The carotenoid zeaxanthin may serve as the chromophore for a photoreceptor involved in blue-light-activated stomatal opening. The properties of these photoreceptors and some of the downstream events they are known to activate are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.33
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  • 9
    Digitale Medien
    Digitale Medien
    MOLECULAR MECHANISMS OF NEURAL CREST FORMATION (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 81-112 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The neural crest is a transient population of multipotent precursor cells named for its site of origin at the crest of the closing neural folds in vertebrate embryos. Following neural tube closure, these cells become migratory and populate diverse regions throughout the embryo where they give rise to most of the neurons and support cells of the peripheral nervous system (PNS), pigment cells, smooth muscle, craniofacial cartilage, and bone. Because of its remarkable ability to generate such diverse derivatives, the neural crest has fascinated developmental biologists for over one hundred years. A great deal has been learned about the migratory pathways neural crest cells follow and the signals that may trigger their differentiation, but until recently comparatively little was known about earlier steps in neural crest development. In the past few years progress has been made in understanding these earlier events, including how the precursors of these multipotent cells are specified in the early embryo and the mechanisms by which they become migratory. In this review, we first examine the mechanisms underlying neural crest induction, paying particular attention to a number of growth factor and transcription factor families that have been implicated in this process. We also discuss when and how the fate of neural crest precursors may diverge from those of nearby neural and epidermal populations. Finally, we review recent advances in our understanding of how neural crest cells become migratory and address the process of neural crest diversification.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.81
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  • 10
    Digitale Medien
    Digitale Medien
    THE ROAD LESS TRAVELED1: Emerging Principles of Kinesin Motor Utilization (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 141-183 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Proteins of the kinesin superfamily utilize a conserved catalytic motor domain to generate movements in a wide variety of cellular processes. In this review, we discuss the rapid expansion in our understanding of how eukaryotic cells take advantage of these proteins to generate force and movement in diverse functional contexts. We summarize several recent examples revealing that the simplest view of a kinesin motor protein binding to and translocating a cargo along a microtubule track is inadequate. In fact, this paradigm captures only a small subset of the many ways in which cells harness force production to the generation of intracellular movements and functions. We also highlight several situations where the catalytic kinesin motor domain may not be used to generate movement, but instead may be used in other biochemical and functional contexts. Finally, we review some recent ideas about kinesin motor regulation, redundancy, and cargo attachment strategies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.141
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  • 11
    Digitale Medien
    Digitale Medien
    VISUAL TRANSDUCTION IN DROSOPHILA (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 231-268 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The Drosophila phototransduction cascade has emerged as an attractive paradigm for understanding the molecular mechanisms underlying visual transduction, as well as other G protein-coupled signaling cascades that are activated and terminated with great rapidity. A large collection of mutants affecting the fly visual cascade have been isolated, and the nature and function of many of the affected gene products have been identified. Virtually all of the proteins, including those that were initially classified as novel, are highly related to vertebrate homologs. Recently, it has become apparent that most of the proteins central to Drosophila phototransduction are coupled into a supramolecular signaling complex, signalplex, through association with a PDZ-containing scaffold protein. The characterization of this complex has led to a re-evaluation of the mechanisms underlying the activation and deactivation of the phototransduction cascade.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.231
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  • 12
    Digitale Medien
    Digitale Medien
    CELL POLARITY IN YEAST (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 365-391 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Subcellular asymmetry, cell polarity, is fundamental to the diverse specialized functions of eukaryotic cells. In yeast, cell polarization is essential to division and mating. As a result, this highly accessible experimental system serves as a paradigm for deciphering the molecular mechanisms underlying the generation of polarity. Beyond yeast, cell polarity is essential to the partitioning of cell fate in embryonic development, the generation of axons and their guidance during neuronal development, and the intimate communication between lymphocytes within the immune system. The polarization of yeast cells shares many features with that of these more complex examples, including regulation by both intrinsic and extrinsic cues, conserved regulatory molecules such as Cdc42 GTPase, and asymmetry of the cytoskeleton as its centerpiece. This review summarizes the molecular pathways governing the generation of cell polarity in yeast.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.365
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  • 13
    Digitale Medien
    Digitale Medien
    WHEN TO SWITCH TO FLOWERING (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 519-550 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract At a certain stage in their life cycle, plants switch from vegetative to reproductive development. This transition is regulated by multiple developmental and environmental cues. These ensure that the plant switches to flowering at a time when sufficient internal resources have been accumulated and the environmental conditions are favorable. The use of a molecular genetic approach in Arabidopsis has resulted in the identification and cloning of many of the genes involved in regulating floral transition. The current view on the molecular function of these genes, their division into different genetic pathways, and how the pathways interact in a complex regulatory network are summarized.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.519
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  • 14
    Digitale Medien
    Digitale Medien
    REGULATION OF MAMMALIAN O2 HOMEOSTASIS BY HYPOXIA-INDUCIBLE FACTOR 1 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 551-578 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic-helix-loop-helix-PAS transcription factor consisting of HIF-1alpha and HIF-1beta subunits. HIF-1alpha expression and HIF-1 transcriptional activity increase exponentially as cellular O2 concentration is decreased. Several dozen target genes that are transactivated by HIF-1 have been identified, including those encoding erythropoietin, glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. The products of these genes either increase O2 delivery or allow metabolic adaptation to reduced O2 availability. HIF-1 is required for cardiac and vascular development and embryonic survival. In fetal and postnatal life, HIF-1 is required for a variety of physiological responses to chronic hypoxia. HIF-1 expression is increased in tumor cells by multiple mechanisms and may mediate adaptation to hypoxia that is critical for tumor progression. HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.551
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  • 15
    Digitale Medien
    Digitale Medien
    MECHANISMS OF VIRAL INTERFERENCE WITH MHC CLASS I ANTIGEN PROCESSING AND PRESENTATION1 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 579-606 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Viruses are ubiquitous and dangerous obligate intracellular parasites. To facilitate recognition of virus-infected cells by the immune system, vertebrates evolved a system that displays oligopeptides derived from viral proteins on the surface of cells in association with class I molecules of the major histocompatibility complex. Here we review the mechanisms counter-evolved by viruses to interfere with the generation of viral peptides, their intracellular trafficking, or the cell surface expression of class I molecules bearing viral peptides. This topic is important in its own right because the viruses that encode these proteins represent medically important pathogens, are potential vectors for vaccines or gene therapy, and provide strategies and tools for blocking immune recognition in transplantation, autoimmunity, and gene therapy. In addition, studies on viral interference provide unique insights into unfettered antigen processing and normal cellular functions that are exploited and exaggerated by viruses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.579
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  • 16
    Digitale Medien
    Digitale Medien
    TRANSPORT BETWEEN THE CELL NUCLEUS AND THE CYTOPLASM (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 607-660 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The compartmentation of eukaryotic cells requires all nuclear proteins to be imported from the cytoplasm, whereas, for example, transfer RNAs, messenger RNAs, and ribosomes are made in the nucleus and need to be exported to the cytoplasm. Nuclear import and export proceed through nuclear pore complexes and can occur along a great number of distinct pathways, many of which are mediated by importin beta-related nuclear transport receptors. These receptors shuttle between nucleus and cytoplasm, and they bind transport substrates either directly or via adapter molecules. They all cooperate with the RanGTPase system to regulate the interactions with their cargoes. Another focus of our review is nuclear export of messenger RNA, which apparently largely relies on export mediators distinct from importin beta-related factors. We discuss mechanistic aspects and the energetics of transport receptor function and describe a number of pathways in detail.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.607
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  • 17
    Digitale Medien
    Digitale Medien
    VACUOLAR IMPORT OF PROTEINS AND ORGANELLES FROM THE CYTOPLASM (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 1-32 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Many cellular processes require a balance between protein synthesis and protein degradation. The vacuole/lysosome is the main site of protein and organellar turnover within the cell due to its ability to sequester numerous hydrolases within a membrane-enclosed compartment. Several mechanisms are used to deliver substrates, as well as resident hydrolases, to this organelle. The delivery processes involve dynamic rearrangements of membrane. In addition, continual adjustments are made to respond to changes in environmental conditions. In this review, we focus on recent progress made in analyzing these delivery processes at a molecular level. The identification of protein components involved in the recognition, sequestration, and transport events has begun to provide information about this important area of eukaryotic cell physiology.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.1
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  • 18
    Digitale Medien
    Digitale Medien
    COOPERATION BETWEEN MICROTUBULE- AND ACTIN-BASED MOTOR PROTEINS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 63-80 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Organelle transport has been proposed to proceed in two steps: long-range transport along microtubules and local delivery via actin filaments. This model is supported by recent studies of pigment transport in several cell types and transport in neurons, and in several cases, class V myosin has been implicated as the actin-based motor. Mutations in mice (dilute) and yeast (myo2) have also implicated this class of myosin in organelle transport, and genetic interactions in yeast have indicated that a kinesin-related protein (Smy1p) plays a supporting role. This link between members of two different motor superfamilies has now taken a surprising turn: There is evidence for a physical interaction between class V myosins and kinesin or Smy1p in both mice and yeast.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.63
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  • 19
    Digitale Medien
    Digitale Medien
    LYMPHOCYTE SURVIVAL-THE STRUGGLE AGAINST DEATH (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 113-140 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Cell proliferation and cell death must be closely regulated to maintain the integrity of the immune system during the lifetime of multicellular organisms. Proliferative expansion of lymphoid cells is required for effective immune responses against invading microorganisms. However, following infection eradication, expanded effector cells must be eliminated to prevent non-adaptive accumulation of cells. Therefore, higher vertebrates have developed an extensive network of signal transduction pathways that allow integration of cell survival and cell death stimuli. This network functions to ensure the controlled activation and expansion of cells during an immune response and the deletion of lymphoid cells that are no longer needed at the end of an immune response. Extracellular signals appear to control both mechanisms. Ultimate responses are integrated through cell surface receptors that are linked to intracellular signaling cascades. These signal transduction pathways converge to regulate cell fate at both transcriptional and post-transcriptional levels. In this review, the role of pathways triggered by TNFR-related molecules that determine the fate of lymphoid cells during development and activation is summarized.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.113
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  • 20
    Digitale Medien
    Digitale Medien
    BIOCHEMICAL PATHWAYS OF CASPASE ACTIVATION DURING APOPTOSIS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 269-290 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Caspase activation plays a central role in the execution of apoptosis. The key components of the biochemical pathways of caspase activation have been recently elucidated. In this review, we focus on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway and the mitochondria-initiated pathway. In the cell surface death receptor pathway, activation of caspase-8 following its recruitment to the death-inducing signaling complex (DISC) is the critical event that transmits the death signal. This event is regulated at several different levels by various viral and mammalian proteins. Activated caspase-8 can activate downstream caspases by direct cleavage or indirectly by cleaving Bid and inducing cytochrome c release from the mitochondria. In the mitochondrial-initiated pathway, caspase activation is triggered by the formation of a multimeric Apaf-1/cytochrome c complex that is fully functional in recruiting and activating procaspase-9. Activated caspase-9 will then cleave and activate downstream caspases such as caspase-3, -6, and -7. This pathway is regulated at several steps, including the release of cytochrome c from the mitochondria, the binding and hydrolysis of dATP/ATP by Apaf-1, and the inhibition of caspase activation by the proteins that belong to the inhibitors of apoptosis (IAP).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.269
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  • 21
    Digitale Medien
    Digitale Medien
    ACTIN-RELATED PROTEINS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 341-363 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Actin-related proteins (Arps) participate in a diverse array of cellular processes. They modulate assembly of conventional actin, contribute to microtubule-based motility catalyzed by dynein, and serve as integral components of large protein complexes required for gene expression. We highlight here recent work aimed at understanding the roles played by Arps in each of these processes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.341
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  • 22
    Digitale Medien
    Digitale Medien
    SCF AND CULLIN/RING H2-BASED UBIQUITIN LIGASES (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 435-467 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Protein degradation is deployed to modulate the steady-state abundance of proteins and to switch cellular regulatory circuits from one state to another by abrupt elimination of control proteins. In eukaryotes, the bulk of the protein degradation that occurs in the cytoplasm and nucleus is carried out by the 26S proteasome. In turn, most proteins are thought to be targeted to the 26S proteasome by covalent attachment of a multiubiquitin chain. Ubiquitination of proteins requires a multienzyme system. A key component of ubiquitination pathways, the ubiquitin ligase, controls both the specificity and timing of substrate ubiquitination. This review is focused on a conserved ubiquitin ligase complex known as SCF that plays a key role in marking a variety of regulatory proteins for destruction by the 26S proteasome.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.435
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  • 23
    Digitale Medien
    Digitale Medien
    NEURAL INDUCTION (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 411-433 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The formation of the vertebrate nervous system is initiated at gastrula stages of development, when signals from a specialized cluster of cells (the organizer) trigger neural development in the ectoderm. This process, termed neural induction, was first described in 1924 and stemmed from experiments on amphibia (Spemann & Mangold 1924). In recent years, the molecular mechanisms underlying neural induction in the amphibian have been elucidated. Surprisingly, neuralizing agents secreted by the organizer do not act via receptor-mediated signaling events; rather, these factors antagonize local epidermal inducers within the cells of the dorsal ectoderm and function to uncover the latent neural fate of these cells. Many of the recent advances in our understanding of vertebrate neural induction come from studies on the frog, Xenopus laevis. It is now clear that a blockade of signaling of the bone morphogenetic proteins (BMPs) during gastrula stages is sufficient to initiate neuralization of the ectoderm in this species. Thus this review first details our current understanding of neural induction, using the amphibian as a model. We then use data emerging from other systems to examine the extent to which the Xenopus studies can be applied to other vertebrate species. The initiation of the neurectoderm-specific gene expression program and subsequent steps in patterning and neuronal development are only touched on here. We focus primarily on the initial establishment of the neural fate in the vertebrate gastrula ectoderm.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.411
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  • 24
    Digitale Medien
    Digitale Medien
    ADAPTORS FOR CLATHRIN-MEDIATED TRAFFIC (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 15 (1999), S. 705-732 
    Details
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Clathrin-based systems are responsible for a large portion of vesicular traffic originating from the plasma membrane and the trans-Golgi network that reaches the endosomal compartment. The assembly of cytosolic clathrin forms the scaffold required for the local deformation of the membrane and for the formation of coated pits and vesicles. In this process, clathrin interacts in a coordinated fashion with a large number of protein partners. A subset designated clathrin adaptors links integral membrane proteins to the clathrin coat, a process that results in the recruitment of specific cargo proteins to the budding vesicle. This review focuses on the most recent advances dealing with the molecular basis for sorting by clathrin adaptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.cellbio.15.1.705
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  • 25
    Digitale Medien
    Digitale Medien
    DISCOVERING THE ORIGINS OF IMMUNOLOGICAL COMPETENCE (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 1-17 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Work done in the late 1950s and in the 1960s revealed the role of the thymus in virus-induced leukemia in mice. Thymectomizing mice at birth to test whether the virus first multiplied in thymus tissue and then spread elsewhere ultimately led to the conclusion that the thymus was essential to the normal development of the immune system. Subsequent testing to try to understand how the thymus contributes to the pool of immunocompetent lymphocytes opened a new chapter in immunology and required a reappraisal of many immunological phenomena and an understanding of the molecular interactions that take place during cell-to-cell interactions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.1
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  • 26
    Digitale Medien
    Digitale Medien
    THE MULTIFACETED REGULATION OF INTERLEUKIN-15 EXPRESSION AND THE ROLE OF THIS CYTOKINE IN NK CELL DIFFERENTIATION AND HOST RESPONSE TO INTRACELLULAR PATHOGENS1 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 19-49 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 alpha-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5' UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15Rbeta and gammac, subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15Ralpha. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.19
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  • 27
    Digitale Medien
    Digitale Medien
    NATURAL KILLER CELLS IN ANTIVIRAL DEFENSE: Function and Regulation by Innate Cytokines (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 189-220 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Natural killer (NK) cells are populations of lymphocytes that can be activated to mediate significant levels of cytotoxic activity and produce high levels of certain cytokines and chemokines. NK cells respond to and are important in defense against a number of different infectious agents. The first indications for this function came from the observations that virus-induced interferons alpha/beta (IFN-alpha and -beta) are potent inducers of NK cell-mediated cytotoxicity, and that NK cells are important contributors to innate defense against viral infections. In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production. Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms. However, high levels of IFN-alpha/beta appear to be unique and/or uniquely dominant in the context of viral infections and act to regulate other innate responses, including induction of NK cell proliferation in vivo and overall negative regulation of IL-12 production. A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.189
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  • 28
    Digitale Medien
    Digitale Medien
    TUMOR NECROSIS FACTOR RECEPTOR AND Fas SIGNALING MECHANISMS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 331-367 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Four members of the tumor necrosis factor (TNF) ligand family, TNF-alpha, LT-alpha, LT-beta, and LIGHT, interact with four receptors of the TNF/nerve growth factor family, the p55 TNF receptor (CD120a), the p75 TNF receptor (CD120b), the lymphotoxin beta receptor (LTbetaR), and herpes virus entry mediator (HVEM) to control a wide range of innate and adaptive immune response functions. Of these, the most thoroughly studied are cell death induction and regulation of the inflammatory process. Fas/Apo1 (CD95), a receptor of the TNF receptor family activated by a distinct ligand, induces death in cells through mechanisms shared with CD120a. The last four years have seen a proliferation in knowledge of the proteins participating in the signaling by the TNF system and CD95. The downstream signaling molecules identified so far-caspases, phospholipases, the three known mitogen activated protein (MAP) kinase pathways, and the NF-kappaB activation cascade-mediate the effects of other inducers as well. However, the molecules that initiate these signaling events, including the death domain- and TNF receptor associated factor (TRAF) domain-containing adapter proteins and the signaling enzymes associated with them, are largely unique to the TNF/nerve growth factor receptor family.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.331
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  • 29
    Digitale Medien
    Digitale Medien
    STRUCTURAL BASIS OF T CELL RECOGNITION (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 369-397 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Exciting breakthroughs in the last two years have begun to elucidate the structural basis of cellular immune recognition. Crystal structures have been determined for full-length and truncated forms of alphabeta T cell receptor (TCR) heterodimers, both alone and in complex with their peptide-MHC (pMHC) ligands or with anti-TCR antibodies. In addition, a truncated CD8 coreceptor has been visualized with a pMHC. Aided in large part by the substantial body of knowledge accumulated over the last 25 years on antibody structure, a number of general conclusions about TCR structure and its recognition of antigen can already be derived from the relatively few TCR structures that have been determined. Small, but important, variations between TCR and antibody structures bear on their functional differences as well as on their specific antigen recognition requirements. As observed in antibodies, canonical CDR loop structures are already emerging for some of the TCR CDR loops. Highly similar docking orientations of the TCR Valpha domains in the TCR/pMHC complex appear to play a primary role in dictating orientation, but the Vbeta positions diverge widely. Similar TCR contact positions, but whose exact amino acid content can vary, coupled with relatively poor interface shape complementarity, may explain the flexibility and short half-lives of many TCR interactions with pMHC. Here we summarize the current state of this field, and suggest that the knowledge gap between the three-dimensional structure and the signaling function of the TCR can be bridged through a synthesis of molecular biological and biophysical techniques.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.369
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  • 30
    Digitale Medien
    Digitale Medien
    GENETIC ANALYSIS OF B CELL ANTIGEN RECEPTOR SIGNALING (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 555-592 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract In B lymphocytes, a signaling complex that contributes to cell fate decisions is the B cell antigen receptor (BCR). Data from knockout experiments in cell lines and mice have revealed distinct functions for the intracellular protein tyrosine kinases (Lyn, Syk, Btk) in BCR signaling and B cell development. Combinations of intracellular signaling pathways downstream of these PTKs determine the quality and quantity of BCR signaling. For example, concerted actions of the PLC-gamma2 and PI3-K pathways are required for proper calcium responses. Similarly, the regulation of ERK and JNK responses involves both PLC-gamma2 and GTPases pathways. Since the immune response in vivo is regulated by alteration of these signaling outcomes, achieving a precise understanding of intracellular molecular events leading to B lymphocyte proliferation, deletion, anergy, receptor editing, and survival still remains a challenge for the future.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.555
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  • 31
    Digitale Medien
    Digitale Medien
    MECHANISMS OF PHAGOCYTOSIS IN MACROPHAGES (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 593-623 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive response. In order to discriminate between infectious agents and self, macrophages have evolved a restricted number of phagocytic receptors, like the mannose receptor, that recognize conserved motifs on pathogens. Pathogens are also phagocytosed by complement receptors after relatively nonspecific opsonization with complement and by Fc receptors after specific opsonization with antibodies. All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle. However, important differences in the molecular mechanisms underlying phagocytosis by different receptors are now being appreciated. These include differences in the cytoskeletal elements that mediate ingestion, differences in vacuole maturation, and differences in inflammatory responses. Infectious agents, such as M. tuberculosis, Legionella pneumophila, and Salmonella typhimurium, enter macrophages via heterogeneous pathways and modify vacuolar maturation in a manner that favors their survival. Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.593
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  • 32
    Digitale Medien
    Digitale Medien
    THE CENTRAL EFFECTORS OF CELL DEATH IN THE IMMUNE SYSTEM (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 781-828 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The immune system relies on cell death to maintain lymphoid homeostasis and avoid disease. Recent evidence has indicated that the caspase family of cysteine proteases is a central effector in apoptotic cell death and is absolutely responsible for many of the morphological features of apoptosis. Cell death, however, can occur through caspase-independent and caspase-dependent pathways. In the case of cells that are irreversibly neglected or damaged, death occurs even in the absence of caspase activity. In contrast, healthy cells require caspase activation to undergo cell death induced by surface receptors. This review summarizes the current understanding of these two pathways of cell death in the immune system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.781
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  • 33
    Digitale Medien
    Digitale Medien
    THE CRYSTAL STRUCTURE OF THE HUMAN HIGH-AFFINITY IgE RECEPTOR (FcepsilonRIalpha) (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 973-976 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.973
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  • 34
    Digitale Medien
    Digitale Medien
    PULLING THE CART AND ENJOYING THE RIDE (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 1-17 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract I was pleased to receive the invitation to write this prefatory chapter. In doing so, I join a number of physiologists whose work and writings I have often admired. There are two aspects of my experience in physiology that I discuss here. The first concerns my own research accomplishments. The second is my role in developing three departments of physiology and fostering the careers of others. While I take pleasure in the former, the overall contribution of the latter was undoubtedly greater.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.1
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  • 35
    Digitale Medien
    Digitale Medien
    CELLULAR AND MOLECULAR BASIS FOR ELECTRICAL RHYTHMICITY IN GASTROINTESTINAL MUSCLES (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 19-43 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Regulation of gastrointestinal (GI) motility is intimately coordinated with the modulation of ionic conductances expressed in GI smooth muscle and nonmuscle cells. Interstitial cells of Cajal (ICC) act as pacemaker cells and possess unique ionic conductances that trigger slow wave activity in these cells. The slow wave mechanism is an exclusive feature of ICC: Smooth muscle cells may lack the basic ionic mechanisms necessary to generate or regenerate slow waves. The molecular identification of the components for these conductances provides the foundation for a complete understanding of the ionic basis for GI motility. In addition, this information will provide a basis for the identification or development of therapeutics that might act on these channels. It is much easier to study these conductances and develop blocking drugs in expression systems than in native GI muscle cells. This review focuses on the relationship between ionic currents in native GI smooth muscle cells and ICC and their molecular counterparts.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.19
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  • 36
    Digitale Medien
    Digitale Medien
    IONIC CONDUCTANCES IN GASTROINTESTINAL SMOOTH MUSCLES AND INTERSTITIAL CELLS OF CAJAL (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 45-84 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Ion channels are the unitary elements that underlie electrical activity of gastrointestinal smooth muscle cells and of interstitial cells of Cajal. The result of ion channel activity in the gastrointestinal smooth muscle layers is a rhythmic change in membrane potential that in turn underlies events leading to organized motility patterns. Gastrointestinal smooth muscle cells and interstitial cells of Cajal express a wide variety of ion channels that are tightly regulated. This review summarizes 20 years of data obtained from patch-clamp studies on gastrointestinal smooth muscle cells and interstitial cells, with a focus on regulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.45
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  • 37
    Digitale Medien
    Digitale Medien
    THE ENTERIC NERVOUS SYSTEM AND REGULATION OF INTESTINAL MOTILITY (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 117-142 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract The enteric nervous system exerts local control over mixing and propulsive movements in the small intestine. When digestion is in progress, intrinsic primary afferent neurons (IPANs) are activated by the contents of the intestine. The IPANs that have been physiologically characterized are in the intrinsic myenteric ganglia. They are numerous, about 650/mm length of small intestine in the guinea pig, and communicate with each other through slow excitatory transmission to form self-reinforcing assemblies. High proportions of these neurons respond to chemicals in the lumen or to tension in the muscle; physiological stimuli activate assemblies of hundreds or thousands of IPANs. The IPANs make direct connections with muscle motor neurons and with ascending and descending interneurons. The circular muscle contracts as an annulus, about 2-3 mm in minimum oral-to-anal extent in the guinea pig small intestine. The smooth muscle cells form an electrical syncytium that is innervated by about 300 excitatory and 400 inhibitory motor neurons per mm length. The intrinsic nerve circuits that control mixing and propulsion in the small intestine are now known, but it remains to be determined how they are programmed to generate the motility patterns that are observed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.117
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  • 38
    Digitale Medien
    Digitale Medien
    MECHANISMS OF CARDIAC PAIN (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 143-167 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Angina pectoris often results from ischemic episodes that excite chemosensitive and mechanoreceptive receptors in the heart. Ischemic episodes release a collage of chemicals, including adenosine and bradykinin, that excites the receptors of the sympathetic and vagal afferent pathways. Sympathetic afferent fibers from the heart enter the upper thoracic spinal cord and synapse on cells of origin of ascending pathways. This review focuses on the spinothalamic tract, but other pathways are excited as well. Excitation of spinothalamic tract cells in the upper thoracic and lower cervical segments, except C7 and C8 segments, contributes to the anginal pain experienced in the chest and arm. Cardiac vagal afferent fibers synapse in the nucleus tractus solitarius of the medulla and then descend to excite upper cervical spinothalamic tract cells. This innervation contributes to the anginal pain experienced in the neck and jaw. The spinothalamic tract projects to the medial and lateral thalamus and, based on positron emission tomography studies, activates several cortical areas, including the anterior cingulate gyrus (BA 24 and 25), the lateral basal frontal cortex, and the mesiofrontal cortex.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.143
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  • 39
    Digitale Medien
    Digitale Medien
    THE CELL BIOLOGY OF THE BLOOD-BRAIN BARRIER (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 11-28 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (ECs). In the late embryonic and early postnatal period, these cells respond to inducing factors found in the brain environment by adopting a set of defined characteristics, including high-electrical-resistance tight junctions. Although the factors have not been identified definitively, a great deal of information about brain ECs has been obtained, especially recently. This review concentrates on a cell biological analysis of the BBB, with an emphasis on regulation of the specialized intercellular junctions. The development of these junctions seems to depend on two primary processes: the appearance of high levels of the tight junction protein occludin and intracellular signaling processes that control the state of phosphorylation of junctional proteins. Recent studies have revealed that the BBB can be modulated in an ongoing way to respond to environmental stimuli.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.11
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  • 40
    Digitale Medien
    Digitale Medien
    MONITORING SECRETORY MEMBRANE WITH FM1-43 FLUORESCENCE (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 1-10 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract FM1-43 and similar styryl dyes have proven useful as probes for membrane trafficking because they reversibly stain membranes, are impermeable to membranes, and are more fluorescent when bound to membranes than when in solution. Because these dyes stain membranes in an activity-dependent manner, they are ideal for studies of neurotransmitter release mechanisms such as synaptic vesicle recycling, exocytosis, and endocytosis. FM dyes have been used in conjunction with other techniques such as fluorescent calcium indicator dyes and electrophysiological techniques to elucidate mechanisms of presynaptic calcium homeostasis and modulation of neurotransmitter release. Presynaptic membranes have been marked by FM dyes in studies of synaptogenesis and reinnervation. As a probe for endocytosed membranes, these dyes have been used to examine vacuole formation in yeast. These versatile membrane dyes are useful in a variety of applications.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.1
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  • 41
    Digitale Medien
    Digitale Medien
    RETINAL WAVES AND VISUAL SYSTEM DEVELOPMENT (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 29-47 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Many pathways in the developing visual system are restructured and become highly organized even before vision occurs. Yet the developmental processes underlying the remodeling of visual connectivity are crucially dependent on retinal activity. Surprisingly, the immature and light-insensitive retina spontaneously generates a pattern of rhythmic bursting activity during the period when the connectivity patterns of retinal ganglion cells are shaped. Spatially, the activity is seen to spread across the retina in the form of waves that bring into synchrony the bursts of neighboring cells. Waves are present in the developing retina of higher and lower vertebrates, which suggests that this form of activity may be a common and fundamental mechanism employed in the activity-dependent refinement of early patterns of visual connections. Unraveling the cues encoded by the waves promises to provide important insights into how interactions driven by specific patterns of activity could lead to the modification of connectivity during development.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.29
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  • 42
    Digitale Medien
    Digitale Medien
    STRESS AND HIPPOCAMPAL PLASTICITY (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 105-122 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-d-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative, episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.105
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  • 43
    Digitale Medien
    Digitale Medien
    MAKING BRAIN CONNECTIONS: Neuroanatomy and the Work of TPS Powell, 1923-1996 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 49-103 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Dr. Thomas PS Powell was one of the founders of modern neuroanatomy. His career spanned an era that saw techniques for analyzing connections in the central nervous system dramatically increase in number and resolving power. In tracing the history of his research, one can see how the introduction of each new technique provided an incremental step in analytical capacity although eventually revealing its own limitations. Also evident is the extent to which prejudices born in the days of applying earlier techniques could continue to influence the interpretation of results obtained with new ones. Powell's contributions to neuroscience were extremely wide-ranging, encompassing investigations of the circuitry of the basal ganglia, corticofugal connections, topographic maps in sensory systems, central olfactory pathways, corticocortical and commissural connections, and pathways for sensory convergence in the cerebral cortex. From these investigations, made with tract tracing techniques, much existing knowledge of forebrain organization is derived. He was also one of the earliest investigators to use electron microscopy in the investigation of the central nervous system, and his electron microscopic studies on the olfactory bulb, thalamus, cerebral cortex, and basal ganglia laid, to a large extent, the foundations for all modern research on the synaptic circuitry of these structures. He was given to synthesizing data across systems in order to arrive at common principles of brain organization. A number of these syntheses have been sources of great interest and, occasionally, controversy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.49
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  • 44
    Digitale Medien
    Digitale Medien
    Airway Wall Mechanics (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 47-72 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract The dimensions, composition, and stiffness of the airway wall are important determinants of airway cross-sectional area during dynamic collapse in a forced expiration or when airway smooth muscle is constricted. Under these circumstances, airway caliber is determined by an interaction between the forces acting to open the airway (parenchymal tension and wall stiffness) and those acting to close it (smooth-muscle force and surface tension at the inner gas-liquid interface). Experimental measurements and theoretical models of the airway tube law (relationship between cross-sectional area and transmural pressure) are presented. Data are presented for the elastic properties of the wall tissue. Simulations of airway constriction in normal and asthmatic airways are discussed. To the extent possible, comparisons are presented between the various models and existing experimental data.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.47
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  • 45
    Digitale Medien
    Digitale Medien
    A Dedication in Memoriam of Dr. Richard Skalak (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 1-18 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Richard Skalak (1923-1997) played a leadership role in the formative decades of the discipline of biomedical engineering through his technical contributions in biomechanics, his educational influence on students, and his service to many developing societies and journals. But always, the distinguishing marks of his involvement with any activity or person were his generosity, respect and tolerance for others, integrity, and curiosity. These very qualities are what first brought him as a traditional engineer trained in engineering mechanics into the young field of biomedical engineering in the 1960s, and they are what led him to new approaches to cellular and molecular engineering, tissue engineering, and orthopedic biomechanics. His technical papers and lectures on blood cell mechanics, pulmonary circulation, dental implants, and tissue growth were models of clarity and often pointed the way to new areas of exploration, while his personal writings offer advice on life, academic organizations, and the pursuit of significant work. He would be deeply appreciative that this first volume of the Annual Review of Biomedical Engineering is dedicated to his memory.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.1
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  • 46
    Digitale Medien
    Digitale Medien
    Tissue Engineering: Orthopedic Applications (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 19-46 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Because of an aging population and increased occurrence of sports-related injuries, musculoskeletal disorders have become one of the major health concerns in the United States. Current treatments, although fairly successful, do not provide the optimum therapy. These treatments typically rely on donor tissues obtained either from the patient or from another source. The former raises the issue of supply, whereas the latter poses the risk of rejection and disease transfer. This has prompted orthopedic surgeons and scientists to look for viable alternatives. In recent years, tissue engineering has gained increasing support as a method to treat orthopedic disorders. Because it uses principles of engineering, biology, and chemistry, tissue engineering may provide a more effective approach to the treatment of musculoskeletal disorders than traditional methods. This chapter presents a review of current methods and new tissue-engineering techniques for the treatment of disorders affecting bone, ligament, and cartilage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.19
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  • 47
    Digitale Medien
    Digitale Medien
    Engineering and Material Considerations in Islet Cell Transplantation (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 103-127 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract The successful application and optimization of cell transplantation will require quantitative engineering design and analysis of cells and materials in which relevant biological processes remain complex and incompletely defined. This report primarily reviews the engineering and material considerations in islet cell transplantation, including established biological constraints and biohybrid devices for cell delivery, as well as available barrier materials and the associated processing strategies directed at the control of solute transport, barrier permeability, and host responses at the biological-material interface. Also described are current areas of investigation with particular promise as enabling technologies for accelerating the clinical effectiveness of islet cell transplantation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.103
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  • 48
    Digitale Medien
    Digitale Medien
    Bioreactors for Hematopoietic Cell Culture (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 129-152 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Hematopoietic cell culture, or ex vivo expansion of hematopoietic cells, is an enabling technology with many potential applications in bone-marrow transplantation, immunotherapy, gene therapy, and the production of blood products. Hematopoietic cultures are complex, with many different cell types at different stages of development present at any given point in time and never in steady state. Moreover, these cells interact strongly with each other and the environment through cytokines (growth factors) and adhesion molecules, as well as through their metabolism. Despite these significant challenges, cell products produced in bioreactors have shown promise in recent phase 1 clinical trials.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.129
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  • 49
    Digitale Medien
    Digitale Medien
    Implanted Electrochemical Glucose Sensors for the Management of Diabetes (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 153-175 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract By maintaining a near normal (70-120 mg/dL) glucose concentration, diabetic patients can drastically reduce the likelihood of the occurrence of diabetes complications. In the near future, subcutaneously implanted electrochemical glucose sensors will be available to provide frequent or continuous information on which timely treatment decisions, such as insulin injection or glucose source intake, can be based, as well as timely alarm signals. The currently engineered devices are of three types: (a) innocuous microsensors, with actively mass-transporting areas 〈10-3 cm2, replaced twice a week by the patient; (b) self-contained, surgeon-implanted, transmitter-containing packages of 〉1 cm2 area, operating for 〉100 days; and (c) devices transporting subcutaneous fluid to an external sensor, based on implanted microfiltration or microdialysis fibers or on iontophoretic transport of the subcutaneous fluid through the skin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.153
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  • 50
    Digitale Medien
    Digitale Medien
    Transport of Molecules, Particles, and Cells in Solid Tumors (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 241-263 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.241
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  • 51
    Digitale Medien
    Digitale Medien
    Injectable Electronic Identification, Monitoring, and Stimulation Systems (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 177-209 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Historically, electronic devices such as pacemakers and neuromuscular stimulators have been surgically implanted into animals and humans. A new class of implants made possible by advances in monolithic electronic design and implant packaging is small enough to be implanted by percutaneous injection through large-gauge hypodermic needles and does not require surgical implantation. Among these, commercially available implants, known as radio frequency identification (RFID) tags, are used for livestock, pet, laboratory animal, and endangered-species identification. The RFID tag is a subminiature glass capsule containing a solenoidal coil and an integrated circuit. Acting as the implanted half of a transcutaneous magnetic link, the RFID tag is powered by and communicates with an extracorporeal magnetic reader. The tag transmits a unique identification code that serves the function of identifying the animal. Millions of RFID tags have been sold since the early 1980s. Based on the success of the RFID tags, research laboratories have developed injectable medical implants, known as micromodules. One type of micromodule, the microstimulator, is designed for use in functional-neuromuscular stimulation. Each microstimulator is uniquely addressable and could comprise one channel of a multichannel functional-neuromuscular stimulation system. Using bidirectional telemetry and commands, from a single extracorporeal transmitter, as many as 256 microstimulators could form the hardware basis for a complex functional-neuromuscular stimulation feedback-control system. Uses include stimulation of paralyzed muscle, therapeutic functional-neuromuscular stimulation, and neuromodulatory functions such as laryngeal stimulation and sleep apnea.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.177
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  • 52
    Digitale Medien
    Digitale Medien
    Fluid Mechanics of Vascular Systems, Diseases, and Thrombosis (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 299-329 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract The cardiovascular system is an internal flow loop with multiple branches circulating a complex liquid. The hallmarks of blood flow in arteries are pulsatility and branches, which cause wall stresses to be cyclical and nonuniform. Normal arterial flow is laminar, with secondary flows generated at curves and branches. Arteries can adapt to and modify hemodynamic conditions, and unusual hemodynamic conditions may cause an abnormal biological response. Velocity profile skewing can create pockets in which the wall shear stress is low and oscillates in direction. Atherosclerosis tends to localize to these sites and creates a narrowing of the artery lumen-a stenosis. Plaque rupture or endothelial injury can stimulate thrombosis, which can block blood flow to heart or brain tissues, causing a heart attack or stroke. The small lumen and elevated shear rate in a stenosis create conditions that accelerate platelet accumulation and occlusion. The relationship between thrombosis and fluid mechanics is complex, especially in the post-stenotic flow field. New convection models have been developed to predict clinical occlusion from platelet thrombosis in diseased arteries. Future hemodynamic studies should address the complex mechanics of flow-induced, large-scale wall motion and convection of semisolid particles and cells in flowing blood.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.299
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  • 53
    Digitale Medien
    Digitale Medien
    Cellular Microtransport Processes: Intercellular, Intracellular, and Aggregate Behavior (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 463-503 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Ionic and molecular transfer among cells occurs by a variety of transport processes operative at different length scales. Cell membrane permeability and electrical conductance derive from channel proteins producing pores at the molecular (ultrastructural) scale. Intracellular mobility involves the dynamics of motion through the complex ultrastructure of the cytoplasm. These phenomena unite in the larger-scale (microscopic) process of gross intercellular transfer. When such movement occurs among sufficiently many cells, it in turn begins to reflect their average collective (macroscopic) behavior as bulk tissue. This article surveys selected aspects of intercellular and intracellular transport, with emphasis on detailed mechanistic theory, experimental probes of cellular permeability, and systematic transcendence from small to large length scales.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.463
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  • 54
    Digitale Medien
    Digitale Medien
    Engineering Design of Optimal Strategies for Blood Clot Dissolution (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 427-461 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Blood clots form under hemodynamic conditions and can obstruct flow during angina, acute myocardial infarction, stroke, deep vein thrombosis, pulmonary embolism, peripheral thrombosis, or dialysis access graft thrombosis. Therapies to remove these clots through enzymatic and/or mechanical approaches require consideration of the biochemistry and structure of blood clots in conjunction with local transport phenomena. Because blood clots are porous objects exposed to local hemodynamic forces, pressure-driven interstitial permeation often controls drug penetration and the overall lysis rate of an occlusive thrombus. Reaction engineering and transport phenomena provide a framework to relate dosage of a given agent to potential outcomes. The design and testing of thrombolytic agents and the design of therapies must account for (a) the binding, catalytic, and systemic clearance properties of the therapeutic enzyme; (b) the dose and delivery regimen; (c) the biochemical and structural aspects of the thrombotic occlusion; (d) the prevailing hemodynamics and anatomical location of the thrombus; and (e) therapeutic constraints and risks of side effects. These principles also impact the design and analysis of local delivery devices.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.427
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  • 55
    Digitale Medien
    Digitale Medien
    Ultrasound Processing and Computing: Review and Future Directions (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 559-588 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Since the introduction of medical ultrasound in the 1950s, modern diagnostic ultrasound has progressed to see many major diagnostic tools come into widespread clinical use, such as B-mode imaging, color-flow imaging, and spectral Doppler. New applications, such as panoramic imaging, three-dimensional imaging, and quantitative imaging, are now beginning to be offered on some commercial ultrasound machines and are expected to grow in popularity. In this review, we focus on the various algorithms, their processing requirements, and the challenges of these ultrasound modes. Whereas the older, mature B and color-flow modes could be systolically implemented using hardwired components and boards, new applications, such as three-dimensional imaging and image feature extraction, are being implemented more by using programmable processors. This trend toward programmable ultrasound machines will continue, because the programmable approach offers the advantages of quick implementation of new applications without any additional hardware and the flexibility to adapt to the changing requirements of these dynamic new applications.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.559
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  • 56
    Digitale Medien
    Digitale Medien
    Instrumentation for the Genome Project (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 649-678 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Much of the recent rapid progress in large-scale genomic sequencing has been driven by the dramatic improvements both in the area of biological protocols and in the availability of improved laboratory instrumentation and automation platforms. We discuss recent developments in the area of bioinstrumentation that are contributing to the current revolution in genetic analysis. Examples of systems for laboratory automation are described together with specific single-purpose instruments. Emphasis is placed on those tools that are contributing significantly to the scale-up of genomic mapping and sequencing efforts. In addition, we present a selection of more advanced measurement techniques and instrumentation developments that are likely to contribute significantly to future advances in sequencing and genome analysis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.649
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  • 57
    Digitale Medien
    Digitale Medien
    MYOBLAST CELL GRAFTING INTO HEART MUSCLE: Cellular Biology and Potential Applications (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 219-242 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract This review surveys a wide range of cellular and molecular approaches to strengthening the injured or weakened heart, focusing on strategies to replace dysfunctional, necrotic, or apoptotic cardiomyocytes with new cells of mesodermal origin. A variety of cell types, including myogenic cell lines, adult skeletal myoblasts, immortalized atrial cells, embryonic and adult cardiomyocytes, embryonic stem cells, teratoma cells, genetically altered fibroblasts, smooth muscle cells, and bone marrow-derived cells have all been proposed as useful cells in cardiac repair and may have the capacity to perform cardiac work. We focus on the implantation of mesodermally derived cells, the best developed of the options. We review the developmental and cell biology that have stimulated these studies, examine the limitations of current knowledge, and identify challenges for the future, which we believe are considerable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.219
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  • 58
    Digitale Medien
    Digitale Medien
    ATP-SENSITIVE POTASSIUM CHANNELS: A Model of Heteromultimeric Potassium Channel/Receptor Assemblies (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 337-362 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract ATP-sensitive K+ channels (KATP channels) play important roles in many cellular functions by coupling cell metabolism to electrical activity. By cloning members of the novel inwardly rectifying K+ channel subfamily Kir6.0 (Kir6.1 and Kir6.2) and the receptors for sulfonylureas (SUR1 and SUR2), researchers have clarified the molecular structure of KATP channels. KATP channels comprise two subunits: a Kir6.0 subfamily subunit, which is a member of the inwardly rectifying K+ channel family; and a SUR subunit, which is a member of the ATP-binding cassette (ABC) protein superfamily. KATP channels are the first example of a heteromultimeric complex assembled with a K+ channel and a receptor that are structurally unrelated to each other. Since 1995, molecular biological and molecular genetic studies of KATP channels have provided insights into the structure-function relationships, molecular regulation, and pathophysiological roles of KATP channels.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.337
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  • 59
    Digitale Medien
    Digitale Medien
    PATHOPHYSIOLOGY OF ENDOTHELIN IN THE CARDIOVASCULAR SYSTEM (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 391-415 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract In this article, we review the basic pharmacological and biochemical features of endothelin and the pathophysiological roles of endothelin in cardiovascular diseases. Development of receptor antagonists has accelerated the pace of investigations into the pathophysiological roles of endogenous endothelin-1 in various diseases, e.g. chronic heart failure, renal diseases, hypertension, cerebral vasospasm, and pulmonary hypertension. In chronic heart failure, the expression of endothelin-1 and its receptors in cardiomyocytes is increased, and treatment with an endothelin receptor antagonist improves survival and cardiac function. Endothelin receptor antagonists also improve other cardiovascular diseases. These results suggest that the interference with endothelin pathway either by receptor blockade or by inhibition of endothelin converting enzyme may provide novel therapeutic drugs strategies for multiple disease states.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.391
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  • 60
    Digitale Medien
    Digitale Medien
    TIMING IN THE AUDITORY SYSTEM OF THE BAT (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 457-476 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Echolocating bats use audition to guide much of their behavior. As in all vertebrates, their lower brainstem contains a number of parallel auditory pathways that provide excitatory or inhibitory outputs differing in their temporal discharge patterns and latencies. These pathways converge in the auditory midbrain, where many neurons are tuned to biologically important parameters of sound, including signal duration, frequency-modulated sweep direction, and the rate of periodic frequency or amplitude modulations. This tuning to biologically relevant temporal patterns of sound is created through the interplay of the time-delayed excitatory and inhibitory inputs to midbrain neurons. Because the tuning process requires integration over a relatively long time period, the rate at which midbrain auditory neurons respond corresponds to the cadence of sounds rather than their fine structure and may provide an output that is closely matched to the rate at which motor systems operate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.457
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  • 61
    Digitale Medien
    Digitale Medien
    SYNAPTIC MECHANISMS FOR CODING TIMING IN AUDITORY NEURONS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 477-496 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Neurons in the cochlear ganglion and auditory brain stem nuclei preserve the relative timing of action potentials passed through sequential synaptic levels. To accomplish this task, these neurons have unique morphological and biophysical specializations in axons, dendrites, and nerve terminals. At the membrane level, these adaptations include low-threshold, voltage-gated potassium channels and unusually rapid-acting transmitter-gated channels, which govern how quickly and reliably action potential threshold is reached during a synaptic response. Some nerve terminals are remarkably large and release large amounts of excitatory neurotransmitter. The high output of transmitter at these terminals can lead to synaptic depression, which may itself be regulated by presynaptic transmitter receptors. The way in which these different cellular mechanisms are employed varies in different cell types and circuits and reflects refinements suited to different aspects of acoustic processing.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.477
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  • 62
    Digitale Medien
    Digitale Medien
    EVOLUTION OF THE VERTEBRATE CARDIO-PULMONARY SYSTEM (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 573-592 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Vertebrate lungs have long been thought to have evolved in fishes largely as an adaptation for life in hypoxic water. This view overlooks the possibility that lungs may have functioned to supply the heart with oxygen and may continue to serve this function in extant fishes. The myocardium of most vertebrates is avascular and obtains oxygen from luminal blood. Because oxygen-rich pulmonary blood mixes with oxygen-poor systemic blood before entering the heart of air-breathing fishes, lung ventilation may supply the myocardium with oxygen and expand aerobic exercise capabilities. Although sustained exercise in tetrapods is facilitated by septation of the heart and the formation of a dual pressure system, a divided cardio-pulmonary system may conflict with myocardial oxygenation because the right side of the heart is isolated from pulmonary oxygen. This may have contributed to the evolution of the coronary circulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.573
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  • 63
    Digitale Medien
    Digitale Medien
    MOUSE MODELS OF AIRWAY RESPONSIVENESS: Physiological Basis of Observed Outcomes and Analysis of Selected Examples Using These Outcome Indicators (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 593-625 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract The mouse is an ideal species for investigation at the interface of lung biology and lung function. As detailed in this review, there are well-developed methods for the quantitative study of lung function in mice. These methods can be applied to mice in both terminal and nonterminal experiments. Terminal experimental approaches provide more detailed physiological information, but nonterminal measurements provide adequate data for certain experiments. In this review, we provide two examples of how these models can be used to further understanding of the primary pathobiology of airway responsiveness in both the absence and the presence of induced airway inflammation. The first model is a dissection of chromosomal loci linked to the variance in airway responsiveness observed in the absence of any manipulation to induce airway inflammation. The second model explores the role of T-cell costimulatory signals in the induction of airway hyperresponsiveness. As the number of mice with targeted deletions of effector genes or insertion of informative transgenes grows, additional examples are likely to accrue.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.593
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  • 64
    Digitale Medien
    Digitale Medien
    ELECTROPHYSIOLOGY OF SYNAPTIC VESICLE CYCLING (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 725-752 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Patch-clamp capacitance measurements can monitor in real time the kinetics of exocytosis and endocytosis in living cells. We review the application of this technique to the giant presynaptic terminals of goldfish bipolar cells. These terminals secrete glutamate via the fusion of small, clear-core vesicles at specialized, active zones of release called synaptic ribbons. We compare the functional characteristics of transmitter release at ribbon-type and conventional synapses, both of which have a unique capacity for fast and focal vesicle fusion. Subsequent rapid retrieval and recycling of fused synaptic vesicle membrane allow presynaptic terminals to function independently of the cell soma and, thus, as autonomous computational units. Together with the mobilization of reserve vesicle pools, local cycling of synaptic vesicles may delay the onset of vesicle pool depletion and sustain neuronal output during high stimulation frequencies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.725
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  • 65
    Digitale Medien
    Digitale Medien
    GENETICS OF SYNAPTIC VESICLE FUNCTION: Toward the Complete Functional Anatomy of an Organelle (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 753-776 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Synaptic transmission starts with the release of neurotransmitters by exocytosis of synaptic vesicles. As a relatively simple organelle with a limited number of components, synaptic vesicles are in principle accessible to complete structural and functional genetic analysis. At present, the majority of synaptic vesicle proteins has been characterized, and many have been genetically analyzed in mice, Drosophila, and Caenorhabditis elegans. These studies have shown that synaptic vesicles contain proteins with diverse structures and functions. Although the genetic studies are as yet unfinished, they promise to lead to a full description of synaptic vesicles as macromolecular machines involved in all aspects of presynaptic neurotransmitter release.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.753
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  • 66
    Digitale Medien
    Digitale Medien
    RECONSTITUTION OF REGULATED EXOCYTOSIS IN CELL-FREE SYSTEMS: A Critical Appraisal (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 777-807 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Regulated exocytosis involves the tightly controlled fusion of a transport vesicle with the plasma membrane. It includes processes as diverse as the release of neurotransmitters from presynaptic nerve endings and the sperm-triggered deposition of a barrier preventing polyspermy in oocytes. Cell-free model systems have been developed for studying the biochemical events underlying exocytosis. They range from semi-intact permeabilized cells to the reconstitution of membrane fusion from isolated secretory vesicles and their target plasma membranes. Interest in such cell-free systems has recently been reinvigorated by new evidence suggesting that membrane fusion is mediated by a basic mechanism common to all intracellular fusion events. In this chapter, we review some of the literature in the light of these new developments and attempt to provide a critical discussion of the strengths and limitations of the various cell-free systems.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.777
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  • 67
    Digitale Medien
    Digitale Medien
    MECHANISMS OF HAIR CELL TUNING (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 809-834 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Mechanosensory hair cells of the vertebrate inner ear contribute to acoustic tuning through feedback processes involving voltage-gated channels in the basolateral membrane and mechanotransduction channels in the apical hair bundle. The specific number and kinetics of calcium-activated (BK) potassium channels determine the resonant frequency of electrically tuned hair cells. Kinetic variation among BK channels may arise through alternative splicing of slo gene mRNA and combination with modulatory beta subunits. The number of transduction channels and their rate of adaptation rise with hair cell response frequency along the cochlea's tonotopic axis. Calcium-dependent feedback onto transduction channels may underlie active hair bundle mechanics. The relative contributions of electrical and mechanical feedback to active tuning of hair cells may vary as a function of sound frequency.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.809
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  • 68
    Digitale Medien
    Digitale Medien
    ION CHANNELS OF NOCICEPTION (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 835-856 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Nociceptors are the first cells in the series of neurons that lead to the sensation of pain. The essential functions of nociceptors-transducing noxious stimuli into depolarizations that trigger action potentials, conducting the action potentials from the peripheral sensory site to the synapse in the central nervous system, and converting the action potentials into neurotransmitter release at the presynaptic terminal-all depend on ion channels. This review discusses recent results in the converging fields of nociception and ion channel biology. It focuses on (a) the capsaicin receptor and its possible role in thermosensation, (b) ATP-gated channels, (c) proton-gated channels, and (d) nociceptor-specific Na+ channels.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.835
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  • 69
    Digitale Medien
    Digitale Medien
    DEVELOPMENT OF THE VERTEBRATE NEUROMUSCULAR JUNCTION (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 389-442 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract We describe the formation, maturation, elimination, maintenance, and regeneration of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses. The NMJ forms in a series of steps that involve the exchange of signals among its three cellular components-nerve terminal, muscle fiber, and Schwann cell. Although essentially any motor axon can form NMJs with any muscle fiber, an additional set of cues biases synapse formation in favor of appropriate partners. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling. NMJs regenerate following damage to nerve or muscle, but this process differs in fundamental ways from embryonic synaptogenesis. Finally, we consider the extent to which the NMJ is a suitable model for development of neuron-neuron synapses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.389
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  • 70
    Digitale Medien
    Digitale Medien
    MOLECULAR BIOLOGY OF ODORANT RECEPTORS IN VERTEBRATES (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 487-509 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The initial step in olfactory discrimination involves the interaction of odorous ligands with specific receptors on the surface of olfactory sensory neurons. The foundation for a molecular understanding of odor recognition in vertebrates was provided by the identification of a family of genes encoding putative odorant receptors, by Buck & Axel in 1991. Odorant receptor (OR) genes form the largest gene family in the vertebrate genome. This review summarizes progress over the past seven years. Major new insights are: Olfaction is accomplished in vertebrates by a very large number of receptors; olfactory sensory neurons express a small subset of the OR repertoire; in rat and mouse, axons of neurons expressing the same OR converge onto defined glomeruli in the olfactory bulb.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.487
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  • 71
    Digitale Medien
    Digitale Medien
    CELLULAR AND MOLECULAR DETERMINANTS OF SYMPATHETIC NEURON DEVELOPMENT1 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 541-566 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The development of the sympathetic nervous system can be divided into three overlapping stages. First, the precursors of sympathetic neurons arise from undifferentiated neural crest cells that migrate ventrally, aggregate adjacent to the dorsal aorta, and ultimately differentiate into catecholaminergic neurons. Second, cell number is refined during a period of cell death when neurotrophic factors determine the number of neuronal precursors and neurons that survive. The final stage of sympathetic development is the establishment and maturation of synaptic connections, which for sympathetic neurons can include alterations in neurotransmitter phenotype. Considerable progress has been made recently in elucidating the cellular and molecular mechanisms that direct each of these developmental decisions. We review the current understanding of each of these, focusing primarily on events in the peripheral nervous system of rodents.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.541
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  • 72
    Digitale Medien
    Digitale Medien
    BIRDSONG AND HUMAN SPEECH: Common Themes and Mechanisms (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 567-631 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Human speech and birdsong have numerous parallels. Both humans and songbirds learn their complex vocalizations early in life, exhibiting a strong dependence on hearing the adults they will imitate, as well as themselves as they practice, and a waning of this dependence as they mature. Innate predispositions for perceiving and learning the correct sounds exist in both groups, although more evidence of innate descriptions of species-specific signals exists in songbirds, where numerous species of vocal learners have been compared. Humans also share with songbirds an early phase of learning that is primarily perceptual, which then serves to guide later vocal production. Both humans and songbirds have evolved a complex hierarchy of specialized forebrain areas in which motor and auditory centers interact closely, and which control the lower vocal motor areas also found in nonlearners. In both these vocal learners, however, how auditory feedback of self is processed in these brain areas is surprisingly unclear. Finally, humans and songbirds have similar critical periods for vocal learning, with a much greater ability to learn early in life. In both groups, the capacity for late vocal learning may be decreased by the act of learning itself, as well as by biological factors such as the hormones of puberty. Although some features of birdsong and speech are clearly not analogous, such as the capacity of language for meaning, abstraction, and flexible associations, there are striking similarities in how sensory experience is internalized and used to shape vocal outputs, and how learning is enhanced during a critical period of development. Similar neural mechanisms may therefore be involved.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.567
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  • 73
    Digitale Medien
    Digitale Medien
    Automatic Implantable Cardioverter-defibrillators (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 331-346 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Ventricular fibrillation, a loss of synchronus electrical activity in the heart which leads to hemodynamic collapse, is a leading cause of death. Because of the devastating personal and societal effects of this phenomenon, the automatic cardioverter-defibrillator has been developed for automatic detection and termination of the arrhythmia and is in widespread clinical use. Advances in circuits, leads, waveforms, and signal processing along with increased knowledge of the mechanisms of fibrillation have led to continuing improvements in this device, extending its use to many patients. A device has also been developed for the automatic or semiautomatic treatment of atrial fibrillation, an arrhythmia less life-threatening than ventricular fibrillation, but still a serious health problem. Continued improvement of these devices and the development of qualitatively new approaches hold great promise for exciting therapeutic advances in this area.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.331
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  • 74
    Digitale Medien
    Digitale Medien
    Microfabrication in Biology and Medicine (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 401-425 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Microfabrication uses integrated-circuit manufacturing technology supplemented by its own processes to create objects with dimensions in the range of micrometers to millimeters. These objects can have miniature moving parts, stationary structures, or both. Microfabrication has been used for many applications in biology and medicine. These applications fall into four domains: tools for molecular biology and biochemistry, tools for cell biology, medical devices, and biosensors. Microfabricated device structures may provide significantly enhanced function with respect to a conventional device. Sometimes microfabrication can enable devices with novel capabilities. These enhancing and enabling qualities are conferred when microfabrication is used appropriately to address the right types of problems. Herein, we describe microfabrication technology and its application to biology and medicine. We detail several classes of advantages conferred by microfabrication and how these advantages have been used to date.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.401
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  • 75
    Digitale Medien
    Digitale Medien
    New Strategies for Protein Crystal Growth (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 505-534 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Protein crystallization is the most difficult and time-consuming step in the determination of a protein's atomic structure. As X-ray diffraction becomes a commonly available tool in structural biology, the necessity for rational methodologies and protocols to produce single, high-quality protein crystals has come to the forefront. The basics of protein crystallization conform to the classical understanding of crystallization of small molecules. Understanding the effect of solution variables such as pH, temperature, pressure, and ionicity on protein solubility allows the proper evaluation of the degree of supersaturation present in protein crystallization experiments. Physicochemical measurements such as laser light scattering, X-ray scattering, X-ray diffraction, and atomic force microscopy provide a clearer picture of protein crystal nucleation and growth. This ever deepening knowledge base is generating rational methods to produce protein crystals as well as means to improve the diffraction quality of such protein crystals. Yet, much remains unclear, and the protein crystallization research community will be quite active for many years to come.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.505
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  • 76
    Digitale Medien
    Digitale Medien
    Imaging Transgenic Animals (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 611-648 
    Details
    ISSN: 1523-9829
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Technik allgemein , Medizin
    Notizen: Abstract Transgenic and eugenic animals as small as 30 g can be studied noninvasively by radionuclides with resolutions of 1-2 mm, by MRI with resolution of 100 mum and by light fluorescence and bioluminescence with high sensitivities. The technologies of radionuclide emission, magnetic resonance imaging, magnetic resonance spectroscopy, optical tomography, optical fluorescence and optical bioluminescence are currently being applied to small-animal studies. These technologies and examples of their applications are reviewed in this chapter.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.611
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  • 77
    Digitale Medien
    Digitale Medien
    INDUCTION OF CYTOCHROME P4501A1 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 103-125 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Cytochrome P4501A1 is a substrate-inducible microsomal enzyme that oxygenates polycyclic aromatic hydrocarbons, such as the carcinogen benzo(a)pyrene, as the initial step in their metabolic processing to water-soluble derivatives. Enzyme induction reflects increased transcription of the cognate CYP1A1 gene. The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin is the most potent known cytochrome P4501A1 inducer. Two regulatory proteins, the aromatic (aryl) hydrocarbon receptor (AhR) and the AhR nuclear translocator (Arnt), mediate induction. AhR and Arnt are prototypical members of the basic helix-loop-helix/Per-Arnt-Sim class of transcription factors. Mechanistic analyses of cytochrome P4501A1 induction provide insights into ligand-dependent mammalian gene expression, basic helix-loop-helix/Per-Arnt-Sim protein function, and dioxin action; such studies also impact public health issues concerned with molecular epidemiology, carcinogenesis, and risk assessment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.103
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  • 78
    Digitale Medien
    Digitale Medien
    REGULATION OF GENE EXPRESSION BY REACTIVE OXYGEN (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 67-101 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Reactive oxygen intermediates are produced in all aerobic organisms during respiration and exist in the cell in a balance with biochemical antioxidants. Excess reactive oxygen resulting from exposure to environmental oxidants, toxicants, and heavy metals perturbs cellular redox balance and disrupts normal biological functions. The resulting imbalance may be detrimental to the organism and contribute to the pathogenesis of disease and aging. To counteract the oxidant effects and to restore a state of redox balance, cells must reset critical homeostatic parameters. Changes associated with oxidative damage and with restoration of cellular homeostasis often lead to activation or silencing of genes encoding regulatory transcription factors, antioxidant defense enzymes, and structural proteins. In this review, we examine the sources and generation of free radicals and oxidative stress in biological systems and the mechanisms used by reactive oxygen to modulate signal transduction cascades and redirect gene expression.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.67
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  • 79
    Digitale Medien
    Digitale Medien
    THE PINEAL GLAND AND MELATONIN: Molecular and Pharmacologic Regulation (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 53-65 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract The pineal gland expresses a group of proteins essential for rhythmic melatonin production. This pineal-specific phenotype is the consequence of a temporally and spacially controlled program of gene expression. Understanding of pineal circadian biology has been greatly facilitated in recent years by a number of molecular studies, including the cloning of N-acetyltransferase, the determination of the in vivo involvement of the cAMP-inducible early repressor in the regulation of N-acetyltransferase, and the identification of a pineal transcriptional regulatory element and its interaction with the cone-rod homeobox protein. Likewise, appreciation the physiological roles of melatonin has increased dramatically with the cloning and targeted knockout of melatonin receptors. With these molecular tools in hand, we can now address more specific questions about how and why melatonin is made in the pineal at night and about how it influences the rest of the body.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.53
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  • 80
    Digitale Medien
    Digitale Medien
    CYTOTOXICITY OF SHORT-CHAIN ALCOHOLS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 127-150 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Ethanol and other short-chain alcohols elicit a number of cellular responses that are potentially cytotoxic and, to some extent, independent of cell type. Aberrations in phospholipid and fatty acid metabolism, changes in the cellular redox state, disruptions of the energy state, and increased production of reactive oxygen metabolites have been implicated in cellular damage resulting from acute or chronic exposure to short-chain alcohols. Resulting disruptions of intracellular signaling cascades through interference with the synthesis of phosphatidic acid, decreases in phosphorylation potential and lipid peroxidation are mechanisms by which solvent alcohols can affect the rate of cell proliferation and, consequently, cell number. Nonoxidative metabolism of short-chain alcohols, including phospholipase D-mediated synthesis of alcohol phospholipids, and the synthesis of fatty acid alcohol esters are additional mechanisms by which alcohols can affect membrane structure and compromise cell function.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.127
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  • 81
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    Digitale Medien
    INHIBITION OF NITRIC OXIDE SYNTHASE AS A POTENTIAL THERAPEUTIC TARGET (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 191-220 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Nitric oxide (NO) regulates numerous physiological processes, including neurotransmission, smooth muscle contractility, platelet reactivity, and the cytotoxic activity of immune cells. Because of the ubiquitous nature of NO, inappropriate release of this mediator has been linked to the pathogenesis of a number of disease states. This provides the rationale for the design of therapies that modulate NO concentrations selectively. A well-characterized family of compounds are the inhibitors of NO synthase, the enzyme responsible for the generation of NO; such agents are potentially beneficial in the treatment of conditions associated with an overproduction of NO, including septic shock, neurodegenerative disorders, and inflammation. This article provides an overview of NO synthase inhibitors, focusing on agents that prevent binding of substrate l-arginine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.191
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  • 82
    Digitale Medien
    Digitale Medien
    GLIAL CELLS IN NEUROTOXICITY DEVELOPMENT (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 151-173 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in a layer of connective tissue. The term, or its shortened form-glia, has persisted as the preferred generic term for these cells. A reciprocal relationship exists between neurons and glia, and this association is vital for mutual differentiation, development, and functioning of these cell types. Therefore, perturbations in glial cell function, as well as glial metabolism of chemicals to active intermediates, can lead to neuronal dysfunction. The purpose of this review is to explore neuroglial sites of neurotoxicant actions, discuss potential mechanisms of glial-induced or glial-mediated central nervous system and peripheral nervous system damage, and review the role of glial cells in neurotoxicity development.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.151
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  • 83
    Digitale Medien
    Digitale Medien
    REGULATION AND INHIBITION OF PHOSPHOLIPASE A2 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 175-189 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract In recent years, there has been great interest in the study of phospholipid metabolism in intact cell systems. Such an interest arises mainly from the discovery that cellular membrane phospholipids serve not only in structural roles, but are also reservoirs of preformed second messenger molecules with key roles in cellular signaling. These second messenger molecules are generated by agonist-induced activation and secretion of intracellular and extracellular phospholipases, respectively, i.e. enzymes that cleave ester bonds within phospholipids. Prominent members of the large collection of signal-activated phospholipases are the phospholipase A2s. These enzymes hydrolyze the sn-2 ester bond of phospholipids, releasing a free fatty acid and a lysophospholipid, both of which may alter cell function. In addition to its role in cellular signaling, phospholipase A2 has recently been recognized to be involved in a wide number of pathophysiological situations, ranging from systemic and acute inflammatory conditions to cancer. A growing number of pharmacologic inhibitors will help define the role of particular phospholipase A2s in signaling cascades.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.175
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  • 84
    Digitale Medien
    Digitale Medien
    REDOX REGULATION OF c-Ha-ras AND OSTEOPONTIN SIGNALING IN VASCULAR SMOOTH MUSCLE CELLS: Implications in Chemical Atherogenesis (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 243-265 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Reduction/oxidation (redox) reactions play a central role in the regulation of vascular cell functions. Recent studies in this laboratory have identified c-Ha-ras and osteopontin genes as critical molecular targets during oxidant-induced atherogenesis. This review focuses on the deregulation of gene transcription by redox-activated trans-acting factors after benzo(a)pyrene challenge and the modulation of extracellular matrix signaling in vascular smooth muscle cells by allylamine-induced oxidative injury. The induction of atherogenic vascular smooth muscle cell phenotypes by chemical injury exhibits remarkable parallels with those seen in other forms of atherogenesis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.243
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  • 85
    Digitale Medien
    Digitale Medien
    GENETIC REGULATION OF GLUTAMATE RECEPTOR ION CHANNELS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 221-241 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Transcriptional and translational regulation of glutamate receptor expression determines one of the key phenotypic features of neurons in the brain-the properties of their excitatory synaptic receptors. Up- and down-regulation of various glutamate receptor subunits occur throughout development, following ischemia, seizures, repetitive activation of afferents, or chronic administration of a variety of drugs. The promoters of the genes that encode the NR1, NR2B, NR2C, GluR1, GluR2, and KA2 subunits share several characteristics that include multiple transcriptional start sites within a CpG island, lack of TATA and CAAT boxes, and neuronal-selective expression. In most cases, the promoter regions include overlapping Sp1 and GSG motifs near the major initiation sites, and a silencer element, to guide expression in neurons. Manipulating the levels of glutamate receptors in vivo by generating transgenic and knockout mice has enhanced understanding of the role of specific glutamate receptor subunits in long-term potentiation and depression, learning, seizures, neural pattern formation, and survival. Neuron-specific glutamate receptor promoter fragments may be employed in the design of novel gene-targeting constructs to deliver future experimental transgene and therapeutic agents to selected neurons in the brain.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.221
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  • 86
    Digitale Medien
    Digitale Medien
    CYCLINS AND CELL CYCLE CHECKPOINTS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 295-312 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract The eucaryotic cell cycle is regulated by the periodic synthesis and destruction of cyclins that associate with and activate cyclin-dependent kinases. Cyclin-dependent kinase inhibitors, such as p21 and p16, also play important roles in cell cycle control by coordinating internal and external signals and impeding proliferation at several key checkpoints. Understanding how these proteins interact to regulate the cell cycle has become increasingly important to researchers and clinicians with the discovery that many of the genes that encode cell cycle regulatory activities are targets for alterations that underlie the development of cancer. Several therapeutic agents, such as DNA-damaging drugs, microtubule inhibitors, antimetabolites, and topoisomerase inhibitors, take advantage of this disruption in normal cell cycle regulation to target checkpoint controls and ultimately induce growth arrest or apoptosis of neoplastic cells. Other therapeutic drugs being developed, such as UCN-01, specifically inhibit cell cycle regulatory proteins.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.295
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  • 87
    Digitale Medien
    Digitale Medien
    METALLOTHIONEIN: An Intracellular Protein to Protect Against Cadmium Toxicity (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 267-294 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Metallothioneins (MT) are low-molecular-weight, cysteine-rich, metal-binding proteins. MT genes are readily induced by various physiologic and toxicologic stimuli. Because the cysteines in MT are absolutely conserved across species, it was suspected that the cysteines are necessary for function and MT is essential for life. In attempts to determine the function(s) of MT, studies have been performed using four different experimental paradigms: (a) animals injected with chemicals known to induce MT; (b) cells adapted to survive and grow in high concentrations of MT-inducing toxicants; (c) cells transfected with the MT gene; and (d) MT-transgenic and MT-null mice. Most often, results from studies using the first three approaches have indicated multiple functions of MT in cell biology: MT (a) is a "storehouse" for zinc, (b) is a free-radical scavenger, and (c) protects against cadmium (Cd) toxicity. However, studies using MT-transgenic and null mice have not strongly supported the first two proposed functions but strongly support its function in protecting against Cd toxicity. Repeated administration of Cd to MT-null mice results in nephrotoxicity at one tenth the dose that produces nephrotoxicity in control mice. Human studies indicate that 7% of the general population have renal dysfunction from Cd exposure. Therefore, if humans did not have MT, "normal" Cd exposure would be nephrotoxic to humans. Thus, it appears that during evolution, the ability of MT to protect against Cd toxicity might have taken a more pivotal role in the maintenance of life processes, as compared with its other proposed functions (i.e. storehouse for zinc and free radical scavenger).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.267
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  • 88
    Digitale Medien
    Digitale Medien
    NEW INSIGHTS INTO DOPAMINERGIC RECEPTOR FUNCTION USING ANTISENSE AND GENETICALLY ALTERED ANIMALS1 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 313-341 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Dopaminergic receptors are widespread throughout the central and peripheral nervous systems, where they regulate a variety of physiological, behavioral, and endocrine functions. These receptors are also clinically important drug targets for the treatment of a number of disorders, such as Parkinson's disease, schizophrenia, and hyperprolactinemia. To date, five different dopamine receptor subtypes have been cloned and characterized. Many of these subtypes are pharmacologically similar, making it difficult to selectively stimulate or block a specific receptor subtype in vivo. Thus, the assignment of various physiological or behavioral functions to specific dopamine receptor subtypes using pharmacological tools is difficult. In view of this, a number of investigators have-in order to elucidate functional roles-begun to use highly selective genetic approaches to alter the expression of individual dopamine receptor subtypes in vivo. This review discusses recent studies involving the use of genetic approaches for the study of dopaminergic receptor function.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.313
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  • 89
    Digitale Medien
    Digitale Medien
    TERATOLOGY OF RETINOIDS (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 399-430 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Either an excess or a deficiency of vitamin A and related compounds (retinoids) causes abnormal morphological development (teratogenesis). Potential retinoid sources come from dietary intake, nutritional supplements, and some therapeutic drugs. Therefore, understanding the mechanisms of retinoid teratogenesis is important. This review first gives an overview of the principles of teratology as they apply to retinoid-induced malformations. It then describes relevant aspects of the biochemical pathway and signal transduction of retinoids. The teratogenic activity of various retinoid compounds, the role of the retinoid receptors, and important toxicokinetic parameters in teratogenesis are reviewed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.399
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  • 90
    Digitale Medien
    Digitale Medien
    BIOCHEMICAL, CELLULAR, AND PHARMACOLOGICAL ASPECTS OF THE MULTIDRUG TRANSPORTER1 (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 361-398 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Considerable evidence has accumulated indicating that the multidrug transporter or P-glycoprotein plays a role in the development of simultaneous resistance to multiple cytotoxic drugs in cancer cells. In recent years, various approaches such as mutational analyses and biochemical and pharmacological characterization have yielded significant information about the relationship of structure and function of P-glycoprotein. However, there is still considerable controversy about the mechanism of action of this efflux pump and its function in normal cells. This review summarizes current research on the structure-function analysis of P-glycoprotein, its mechanism of action, and facts and speculations about its normal physiological role.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.361
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  • 91
    Digitale Medien
    Digitale Medien
    beta-ADRENERGIC RECEPTORS AND RECEPTOR SIGNALING IN HEART FAILURE (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 343-360 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract Cardiac beta-adrenergic receptors, which respond to neuronally released and circulating catecholamines, are important regulators of cardiac function. Congestive heart failure, a common clinical condition, is associated with a number of alterations in the activation and deactivation of beta-adrenergic receptor pathways. Studies with failing hearts from humans and animals indicate that such alterations include changes in the expression or function of beta-adrenergic receptors, G-proteins, adenylyl cyclases, and G-protein receptor kinases. The net effect of these alterations is the substantial blunting of beta-adrenergic receptor-mediated cardiac response. An important unanswered question is whether the loss of cardiac beta-adrenergic receptor responsiveness is a contributing cause, or a result, of ventricular dysfunction. Even though this question remains unanswered, the concept of targeting the beta-adrenergic pathway in the failing heart is becoming increasingly popular and several new therapeutic strategies are in development.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.343
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  • 92
    Digitale Medien
    Digitale Medien
    EXCITATORY AMINO ACID TRANSPORTERS: A Family in Flux (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 39 (1999), S. 431-456 
    Details
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Abstract As the most predominant excitatory neurotransmitter, glutamate has the potential to influence the function of most neuronal circuits in the central nervous system. To limit receptor activation during signaling and prevent the overstimulation of glutamate receptors that can trigger excitotoxic mechanisms and cell death, extracellular concentrations of excitatory amino acids are tightly controlled by transport systems on both neurons and glial cells. l-Glutamate is a potent neurotoxin, and the inadequate clearance of excitatory amino acids may contribute to the neurodegeneration seen in a variety of conditions, including epilepsy, ischemia, and amyotrophic lateral sclerosis. To establish the contributions of carrier systems to the etiology of neurological disorders, and to consider their potential utility as therapeutic targets, a detailed understanding of transporter function and pharmacology is required. This review summarizes current knowledge of the structural and functional diversity of excitatory amino acid transporters and explores how they might serve as targets for drug design.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.39.1.431
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  • 93
    Digitale Medien
    Digitale Medien
    THE WISKOTT-ALDRICH SYNDROME PROTEIN (WASP): Roles in Signaling and Cytoskeletal Organization (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 905-929 
    Details
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency that is characterized by recurrent infections, hematopoietic malignancies, eczema, and thrombocytopenia. A variety of hematopoietic cells are affected by the genetic defect, including lymphocytes, neutrophils, monocytes, and platelets. Early studies noted both signaling and cytoskeletal abnormalities in lymphocytes from WAS patients. Following the identification of WASP, the gene mutated in patients with this syndrome, and the more generally expressed WASP homologue N-WASP, studies have demonstrated that WASP-family molecules associate with numerous signaling molecules known to alter the actin cytoskeleton. WASP/N-WASP may depolymerize actin directly and/or serve as an adaptor or scaffold for these signaling molecules in a complex cascade that regulates the cytoskeleton.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.immunol.17.1.905
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  • 94
    Digitale Medien
    Digitale Medien
    REGULATION OF NATRIURETIC PEPTIDE SECRETION BY THE HEART (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 193-217 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Secreted by the heart, more specifically by atrial cardiomyocytes under normal conditions but also by ventricular myocytes during cardiac hypertrophy, natriuretic peptides are now considered important hormones in the control of blood pressure and salt and water excretion. Studies on natriuretic peptide secretagogues and their mechanisms of action have been complicated by hemodynamic changes and contractions to which the atria are constantly subjected. It now appears that atrial stretch through mechano-sensitive ion channels, adrenergic stimulation via alpha1A-adrenergic receptors, and endothelin via its ETA receptor subtype are major triggering agents of natriuretic peptide release. With several other stimuli, such as angiotensin II and beta-adrenergic agents, modulation of natriuretic peptide release appears to be linked to local generation of prostaglandins. In all cases, intracellular calcium homeostasis, controlled by several ion channels, is considered a key element in the regulation of natriuretic peptide secretion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.193
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  • 95
    Digitale Medien
    Digitale Medien
    TIMING OF SYNAPTIC TRANSMISSION (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 521-542 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Many behaviors require rapid and precisely timed synaptic transmission. These include the determination of a sound's direction by detecting small interaural time differences and visual processing, which relies on synchronous activation of large populations of neurons. In addition, throughout the brain, concerted firing is required by Hebbian learning mechanisms, and local circuits are recruited rapidly by fast synaptic transmission. To achieve speed and precision, synapses must optimize the many steps between the firing of a presynaptic cell and the response of its postsynaptic targets. Until recently, the behavior of mammalian synapses at physiological temperatures was primarily extrapolated from studies at room temperature or from the properties of invertebrate synapses. Recent studies have revealed some of the specializations that make synapses fast and precise in the mammalian central nervous system at physiological temperatures.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.521
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  • 96
    Digitale Medien
    Digitale Medien
    THE ROLE OF TIMING IN THE BRAIN STEM AUDITORY NUCLEI OF VERTEBRATES (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 497-519 
    Details
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Vertebrate animals gain biologically important information from environmental sounds. Localization of sound sources enables animals to detect and respond appropriately to danger, and it allows predators to detect and localize prey. In many species, rapidly fluctuating sounds are also the basis of communication between conspecifics. This information is not provided directly by the output of the ear but requires processing of the temporal pattern of firing in the tonotopic array of auditory nerve fibers. The auditory nerve feeds information through several parallel ascending pathways. Anatomical and electrophysiological specializations for conveying precise timing, including calyceal synaptic terminals and matching axonal conduction times, are evident in several of the major ascending auditory pathways through the ventral cochlear nucleus and its nonmammalian homologues. One pathway that is shared by all higher vertebrates makes an ongoing comparison of interaural phase for the localization of sound in the azimuth. Another pathway is specifically associated with higher frequency hearing in mammals and is thought to make use of interaural intensity differences for localizing high-frequency sounds. Balancing excitation from one ear with inhibition from the other in rapidly fluctuating signals requires that the timing of these synaptic inputs be matched and constant for widely varying sound stimuli in this pathway. The monaural nuclei of the lateral lemniscus, whose roles are not understood (although they are ubiquitous in higher vertebrates), receive input from multiple pathways that encode timing with precision, some through calyceal endings.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.497
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  • 97
    Digitale Medien
    Digitale Medien
    ETIOLOGY AND PATHOGENESIS OF PARKINSON'S DISEASE (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 123-144 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Parkinson's disease (PD) is an age-related neurodegenerative disorder that affects approximately 1 million persons in the United States. It is characterized by resting tremor, rigidity, bradykinesia or slowness, gait disturbance, and postural instability. Pathological features include degeneration of dopaminergic neurons in the substantia nigra pars compacta coupled with intracytoplasmic inclusions known as Lewy bodies. Neurodegeneration and Lewy bodies can also be found in the locus ceruleus, nucleus basalis, hypothalamus, cerebral cortex, cranial nerve motor nuclei, and central and peripheral components of the autonomic nervous system. Current treatment consists of a dopamine replacement strategy using primarily the dopamine precursor levodopa. While levodopa provides benefit to virtually all PD patients, after 5-10 years of treatment the majority of patients develop adverse events in the form of dyskinesia (involuntary movements) and fluctuations in motor response. Further, disease progression is associated with the development of dementia, autonomic dysfunction, and postural instability, which do not respond to levodopa therapy. Accordingly, research efforts have been directed toward understanding the etiology and pathogenesis of PD in the hope of developing a more effective therapy that will slow or halt the natural progression of PD. This paper reviews recent advances.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.123
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  • 98
    Digitale Medien
    Digitale Medien
    COMPUTATIONAL NEUROIMAGING OF HUMAN VISUAL CORTEX (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 145-173 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Functional magnetic resonance imaging is a new neuroimaging method for probing the intact, alert, human brain. With this tool, brain activity that has been hidden can now be measured. Recent advances in measuring and understanding human neural responses underlying motion, color, and pattern perception are reviewed. In individual human brains, we can now identify the positions of several retinotopically organized visual areas; measure retinotopic organization within these areas; identify the location of a motion-sensitive region in individual brains; measure responses associated with contrast, color, and motion; and measure effects of attentional modulation on visually evoked responses. By framing experiments and analyses as questions about visual computation, these neuroimaging measurements can be coupled closely with those from other basic vision-science methods.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.145
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  • 99
    Digitale Medien
    Digitale Medien
    MONOAMINE OXIDASE: From Genes to Behavior (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 197-217 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B knock-out mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A. In contrast, MAO B knock-out mice do not exhibit aggression and only levels of phenylethylamine are increased. Mice lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Both MAO A and B knock-out mice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.197
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  • 100
    Digitale Medien
    Digitale Medien
    MICROGLIA AS MEDIATORS OF INFLAMMATORY AND DEGENERATIVE DISEASES (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 22 (1999), S. 219-240 
    Details
    ISSN: 0147-006X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Microglia are the principal immune cells in the central nervous system (CNS) and have a critical role in host defense against invading microorganisms and neoplastic cells. However, as with immune cells in other organs, microglia may play a dual role, amplifying the effects of inflammation and mediating cellular degeneration as well as protecting the CNS. In entities like human immunodeficiency virus (HIV) infection of the nervous system, microglia are also critical to viral persistence. In this review we discuss the role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1146/annurev.neuro.22.1.219
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