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  • 1
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 2 (1996), S. 467-469 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (ΔF508), causes severe CF and resides on 70% of mutant chromosomes. Severe CF is also caused by premature ...
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 2 (1996), S. 608-609 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Bed-well and colleagues reply — The abundance of many mRNAs containing premature stop mutations is reduced when compared to the corresponding wild type mRNA. Various models have been proposed to explain this observation, and it is possible that nonsense codons within different mRNAs can ...
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 10 (2004), S. 452-454 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Despite advances over the last few decades, patients with cystic fibrosis typically die of obstructive lung disease by their mid-30s. Following discovery of the responsible gene in 1989, the work of many scientists implicated the cystic fibrosis transmembrane conductance regulator (CFTR) as a ...
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 372 (1981), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
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  • 5
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1 Time course of voltage-induced Cl~ channel activation. Successive records were obtained at times shown at the right margin and at holding potentials given at the left margin. Membrane voltage is expressed with respect to pipette as reference; upward current deflections are outward currents, ...
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 350 (1991), S. 277-278 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE product of the gene that is defective in cystic fibrosis may be a chloride channel. This is the implication of new work, reported by Anderson et at.1 in Science* and by Kart-ner etal. in Cell2, showing that expression of the cystic fibrosis gene in nonepithelial cells endows them with a plasma ...
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  • 7
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Flounder intestine is morphologically less heterogeneous than the intestines of higher vertebrates; in particular, it contains no crypts11. (Possibly for this reason, it cannot be stimulated to secrete NaCl and water12, differing in this respect from avian and mammalian intestine, both of which ...
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 33 (1977), S. 351-384 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The electrophysiologic properties of rabbit colonic epithelial cells were investigated employing microelectrode techniques. Under open-circuit conditions, the transepithelial electrical potential difference (PD) averaged 20 mV, serosa positive, and the intracellular electrical potential (ψ mc ) averaged −32 mV, cell interior negative with respect to the mucosal solution; under short-circuit conditions,ψ mc averaged −46 mV. The addition of amiloride to the mucosal solution abolishes the transepithelialPD and active Na transport, andψ mc is hyperpolarized to an average value of −53 mV. These results indicate that Na entry into the mucosal cell is a conductive process which, normally, depolarizesψ mc . The data obtained were interpreted using a double-membrane equivalent electrical circuit model of the “active Na transport pathway” involving two voltage-independent electromotive forces (emf's) and two voltage-independent resistances arrayed in series. Our observations are consistent with the notions that: (a) The emf's and resistances across the mucosal and baso-lateral membranes are determined predominantly by the emf (64mV) and resistance of the Na entry process and the emf (53 mV) and resistance of the process responsible for active Na extrusion across the baso-lateral membranes: that is, the electrophysiological properties of the cell appear to be determined solely by the properties and processes responsible for transcellular active Na transport. The emf of the Na entry process is consistent with the notion that the Na activity in the intracellular transport pool is approximately one-tenth that in the mucosal solution or about 14mM. (b) In the presence of amiloride, the transcellular conductance is essentially abolished and the total tissue conductance is the result of ionic diffusion through paracellular pathways. (c) The negative intracellular potential (with respect to the mucosal solution) is due primarily to the presence of a low resistance paracellular “shunt” pathway which permits electrical coupling between the emf at the baso-lateral membrane and the potential difference across the mucosal membrane; in the absence of this shunt, the “well-type” electrical potential profile characteristic of rabbit colonic cells would be ‘converted’ into a “staircase-type” profile similar to those reported for frog skin and toad urinary bladder by some investigators.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 46 (1979), S. 27-39 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Measurements of the unidirectional influxes of Na and Cl from the mucosal solution into the epithelium (J me ) of flounder intestine under short-circuit conditions reveal the presence of a coupled NaCl influx process at the brush border membrane which appears to be essential for the absorption of these ions.J me Cl andJ me Na were inhibited by replacing Na or Cl, respectively, in the bathing media with nontransported ions which also reduced the short-circuit current (I sc) to near-zero values. Addition of furosemide to the mucosal solution alone inhibited theI sc and reducedJ me Cl andJ me Na under control conditions, but not in the absence of Na or Cl, respectively. The reductions inJ me Cl andJ me Na elicited by ion replacement or furosemide were approximately equal, suggesting that the coupled influx mechanism mediates a one-for-one entry of these ions into the cell from the mucosal solution. Furosemide inhibited Cl absorption by reducing the unidirectional Cl flux from mucosa to serosa, consistent with its inhibition of the influx process. As in other epithelia, coupled NaCl influx is inhibited by cyclic AMP, which accounts for the decrease in Cl absorption elicited by cyclic nucleotides. These results support the notion thattranscellular NaCl transport is a neutral process and that the serosa-negative transepithelial electrical potential difference and preponderance of Cl over Na absorption under short-circuit conditions result from dissimilar permeabilities of the paracellular pathway to Na and Cl.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 71 (1983), S. 209-218 
    ISSN: 1432-1424
    Keywords: tracheal epithelium ; Cl secretion ; electrophysiology ; equivalent electrical circuit ; epinephrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary We used intracellular microelectrode techniques and equivalent electrical circuit analysis to examine the changes in individual membrane resistances and electromotive forces that accompany stimulation of Cl secretion across canine tracheal epithelium. Tissues were pretreated with indomethacin (10−6 m, mucosal solution) to reduce basel Cl secretion rate. Subsequent addition of epinephrine (10−6 m, submucosal solution) increased the rate of electrogenic Cl secretion as indicated by an increase in the short-circuit current (I sc) and decrease in the transepithelial resistance (R t ). The reduction inR t was due to decreases in bothR a andR b (the resistances of the apical and basolateral cell membranes, respectively). At the apical membrane, a nearly 10-fold decrease inR a was accompanied by reversal of the electromotive force (E a ) from +11±9 mV to −31±3 mV. Variations in Cl secretion rate induced by indomethacin and epinephrine disclosed a direct relation betweenR a andE a . In the presence of indomethacinR a was high andE a was consistent with the chemical potential difference for Na across the apical membrane (ca. +60 mV), reflecting the predominance of Na absorption across indomethacin-treated tissues. In the presence of epinephrine,R a was low andE a was consistent with the chemical potential difference for Cl across this barrier (−31 mV), reflecting the dominance of Cl secretion across epinephrine-treated tissues. These findings suggest that the conversion from absorption to secretion primarily involves a secretogogue-induced decrease in apical membrane resistance to Cl. At the basolateral membrane, epinephrine decreasedR b threefold without markedly altering the electromotive force across this barrier (E b ). To the extent thatR b andE b represent the resistance and chemical potential difference for K diffusion across the basolateral membrane, the inverse relation betweenR b andI sc suggests that stimulation is associated with increased basolateral membrane K permeability without marked changes in intracellular K activity.
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