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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 116 (1990), S. 107-115 
    ISSN: 1432-1424
    Keywords: sodium-hydrogen exchange ; red cells ; sickle cell anemia ; erythrocyte ; reticulocyte ; cation transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Red cell volume regulation is important in sickle cell anemia because the rate and extent of HbS polymerization are strongly dependent on initial hemoglobin concentration. We have demonstrated that volume-sensitive K:Cl cotransport is highly active in SS whole blood and is capable of increasing MCHC. We now report that Na+/H+ exchange (Na/H EXC), which is capable of decreasing the MCHC of erythrocytes with pHi〈7.2, is also very active in the blood of patients homozygous for HbS. The activity of Na/H EXC (maximum rate) was determined by measuring net Na+ influx (mmol/liter cell·hr=FU) driven by an outward H+ gradient in oxygenated, acidloaded (pHi 6.0), DIDS-treated SS cells. The Na/H EXC activity was 33±3 FU (mean±se) (n=19) in AA whites, 37±8 FU (n=8) in AA blacks, and 85±15 FU (n=14) in SS patients (P〈0.005). Separation of SS cells into four density-defined fractions by density gradient revealed mean values of Na/H EXC four to five times higher in reticulocytes (SS1), discocytes (SS2) and dense discocytes (SS3), than in the fraction containing irreversibly sickled cells and dense discocytes (SS4). In contrast to K:Cl cotransport, which dramatically decreases after reticulocyte maturation, Na/H EXC persists well after reticulocyte maturation. In density-defined, normal AA red cells, Na/H EXC decreased monotonically as cell density increased. In SS and AA red cells, the magnitude of stimulation of Na/H EXC by cell shrinkage varied from individual to individual. We conclude that Na/H EXC is highly expressed in SS and AA young red cells and decays slowly after reticulocyte maturation.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 106 (1988), S. 219-231 
    ISSN: 1432-1424
    Keywords: sodium transport ; fibroblasts ; H.Ep.2 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Na+ transport was characterized in normal human fibroblasts and neoplastic H.Ep. 2 cells in order to investigate the role of the endogenous peptidic factor ‘inhibitin’ that is secreted by a variety of neoplastic cells (including H.Ep. 2) and inhibits Na+/Na+ exchange in human erythrocytes. Although active (Na+, K+-ATPase mediated) Na+ fluxes were similar in the two cell types, H.Ep. 2 cells maintained higher intracellular Na[su+] concentration (26mm) compared to fibroblasts (12mm). An analysis of passive Na+ fluxes showed a difference in the handling of Na+ via ouabain and bumetanide-insensitive transport between the two cell types: H.Ep. 2 cells achieved net Na+ influx via an amiloride-sensitive pathway that was only demonstrated in fibroblasts when 10% fetal calf serum (FCS) was present. Kinetic studies were undertaken to investigate the interaction between Na+ flux via Na+/H+ and Na+/Na+ exchanges. for this purpose, an outwardly directed Na+ gradient was created by loading the cells with Na+ (Na i 〉100mm) to activate the reverse functioning of Na+/H+ exchange (i.e., Na out + H in + ). The rates of ouabain-and bumetanide-insensitive Na+ efflux were measured over a range of extracellular Na+ concentrations (Na o + 14–140mm). In the presence of 10% FCS, the two cell types showed different responses: in fibroblasts the Na+ efflux rate showed an inverse correlation with extracellular Na+ concentration, while H.Ep. 2 cells significantly increased their rate of Na+ efflux as extracellular Na+ concentration increased. So although the thermodynamic force would direct net Na+ efflux when Na i + 〉Na o + , H.Ep.2 cells were under kinetic control to perform Na+/Na+ exchange. When exogenous inhibitin was tested on fibroblasts, the steady-state intracellular Na+ concentration increased from 14 to 19mm (p〈0.01). In Na+-loaded fibroblasts, serum-stimulated Na+ efflux was partially inhibitin sensitive and the maximal inhibitory effect was seen when extracellular Na+ concentration was 14mm and presumably the Na+/H+ exchanger operating in the reverse mode. This study demonstrated that, in contrast to fibroblasts, H.Ep.2 cells have a modified Na+/H+ exchange system whereby it acts in the Na in + H out + mode without exogenous growth factor activation and resists functioning in the reversed mode. It is proposed that inhibitin, is the endogenous modifier of this transport system in H.Ep.2 cells with the result that H.Ep.2 cells maintain a higher concentration of intracellular Na+ compared to fibroblasts.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 92 (1986), S. 163-170 
    ISSN: 1432-1424
    Keywords: sodium transport ; serum stimulation ; fibroblasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The relationships between intracellular sodium content, sodium transport and serum effects were investigated in human fibroblasts. In the cells with low intracellular sodium (Na iL /+ ;0.04 μmol sodium/mg protein) serum stimulated the sodium-potassium pump as measured by ouabain-sensitive sodium efflux and rubidium influx and also exerted a transstimulation of ouabain-insensitive sodium transport resulting in net influx. In cells with high intracellular sodium (Na iH /+ ;0.42 μmol sodium/mg protein) all aspects of sodium transport were increased compared to Na iL /+ cells. In these cells serum caused no change in sodium-potassium pump activity but significantly increased the ouabain-insensitive sodium fluxes resulting in net efflux. In Na iL /+ cells, serum promoted net sodium influx through an amiloride-sensitive pathway that was undetectable in the basal state. In Na iH /+ cells the serum-stimulated net efflux was amiloride sensitive but this pathway also contributed to a major portion of sodium transport in the basal state. This study demonstrated that sodium-potassium pump activity is directed by the supply of internal sodium and that serum can increase this supply by promoting net influx, and that serum-induced sodium transport can be modified by intracellular sodium content.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 118 (1990), S. 193-214 
    ISSN: 1432-1424
    Keywords: rabbit red cells ; Na/Na exchange ; Na/H exchange ; H+ and Na+ interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary We have studied the kinetic properties of rabbit red cell (RRBC) Na+/Na+ and Na+/H+ exchanges (EXC) in order to define whether or not both transport functions are conducted by the same molecule. The strategy has been to determine the interactions of Na+ and H+ at the internal (i) and external (o) sites for both exchanges modes. RRBC containing varying Na i and H l were prepared by nystatin and DIDS treatment of acid-loaded cells. Na+/Na+ EXC was measured as Na o -stimulated Na+ efflux and Na+/H+ EXC as Na o -stimulated H+ efflux and ΔpH o -stimulated Na+ influx into acid-loaded cells. The activation of Na+/Na+ EXC by Na o at pH i 7.4 did not follow simple hyperbolic kinetics. Testing of different kinetic models to obtain the best fit for the experimental data indicated the presence of high (K m 2.2 mM) and low affinity (K m 108 mM) sites for a single- or two-carrier system. The activation of Na+/H+ EXC by Na o (pH i 6.6, Na i 〈1 mM) also showed high (K m 11 mM) and low (K m 248 mM) affinity sites. External H+ competitively inhibited Na+/Na+ EXC at the low affinity Na o site (K H 52 nM) while internally H+ were competitive inhibitors (pK 6.7) at low Na i and allosteric activators (pK 7.0) at high Na i . Na+/H+ EXC was also inhibited by acid pH o and allosterically activated by H i (pK 6.4). We also established the presence of a Na i regulatory site which activates Na+/H+ and Na+/Na+ EXC modifying the affinity for Na o of both pathways. At low Na i , Na+/Na+ EXC was inhibited by acid pH i and Na+/H+ stimulated but at high Na i , Na+/Na+ EXC was stimulated and Na+/H+ inhibited being the sum of both pathways kept constant. Both exchange modes were activated by two classes of Na o sites,cis-inhibited by external H o , allosterically modified by the binding of H+ to a H i regulatory site and regulated by Na i . These findings are consistent with Na+/Na+ EXC being a mode of operation of the Na+/H+ exchanger. Na+/H+ EXC was partially inhibited (80–100%) by dimethyl-amiloride (DMA) but basal or pH i -stimulated Na+/Na+ EXC (pH i 6.5, Na i 80 mM) was completely insensitive indicating that Na+/Na+ EXC is an amiloride-insensitive component of Na+/H+ EXC. However, Na+ and H+ efflux into Na-free media were stimulated by cell acidification and also partially (10 to 40%) inhibited by DMA: this also indicates that the Na+/H+ EXC might operate in reverse or uncoupled modes in the absence of Na+/Na+ EXC. In summary, the observed kinetic properties can be explained by a model of Na+/H+ EXC with several conformational states, H i and Na i regulatory sites and loaded/unloaded internal and external transport sites at which Na+ and H+ can compete. The occupancy of the H+ regulatory site induces a conformational change and the occupancy of the Na i regulatory site modulates the flow through both pathways so that it will conduct Na+/H+ and/or Na+/Na+ EXC depending on the ratio of internal Na+:H+.
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  • 5
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A variant of the apolipoprotein E gene, APOE*4, is associated with both sporadic Alzheimer’s disease (AD) and a subset of familial AD and this association is stronger with early as opposed to late onset AD. Both APOE*4 and α1-antichymotrypsin (ACT) will accelerate the rate of amyloid filament formation and are major constituents of the plaques associated with AD. We now show that a dinucleotide microsatellite allele in the 5′-flanking sequence of the ACT gene, designated A10, in association with APOE*4 significantly increases the risk of developing sporadic AD, which accounts for the majority of AD cases.
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  • 6
    Electronic Resource
    Electronic Resource
    Bradford : Emerald
    British food journal 102 (2000), S. 40-51 
    ISSN: 0007-070X
    Source: Emerald Fulltext Archive Database 1994-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Describes self-reported dietary supplement use among elderly people in the UK and explores the association between supplement use and socioeconomic, physical and dietary factors. A three-phase survey incorporating face-to-face interviews, self-completed four-day dietary diaries with a food frequency questionnaire and follow-up face-to-face interviews took place in urban Nottingham and rural Nottinghamshire, Lincolnshire and Leicestershire. A total of 957 elderly people (aged over 65) were randomly selected from general practitioner lists. A total of 36 per cent of the urban respondents and 41 per cent of rural respondents were taking at least one dietary supplement. Respondents who did not smoke were of a higher social class and had more qualifications were the most likely to take supplements. Fish oil was the most commonly taken supplement, followed by multivitamins, garlic tablets and vitamin C. The mean dietary intake of all respondents was above the reference nutrient intakes (RNIs) for nutrients studied. The diets of supplement users, excluding nutrients derived from supplementation, contained more iron, vitamin C, fibre, folate and oily fish than non-users. Dietary supplement usage is widespread among the UK elderly, although supplement users within this sample do not appear to have diets which warrant supplementation to meet RNIs in the nutrients studied. Many advantages are, however, reported of consuming fish oils, garlic and higher intakes of anti-oxidants.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 14 (1994), S. 0 
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Formaldehyde is a nasal carcinogen in the rat but the cancer risk this chemical poses for humans remains to be determined. Formaldehyde induces nonlinear, concentration-dependent increases in nasal epithelial cell proliferation and DNA-protein cross-link formation following short-term exposure. Presented in this review are results from a mechanistically based formaldehyde inhalation study in which an important endpoint was the measurement of cell proliferation indices in target sites for nasal tumor induction. Male Fischer 344 rats were exposed to 0, 0.7, 2, 6, 10, or 15 ppm formaldehyde for up to 2 years (6 hr/day, 5 day/week). Statistically significant increases in cell proliferation were confined to the 10 and 15 ppm groups, which remained elevated throughout the study. The concentration-dependent increases in cell proliferation correlated strongly with the tumor response curve, supporting the proposal that sustained increases in cell proliferation are an important component of formaldehyde carcinogenesis. The nonlinearity observed in formaldehyde-induced rodent nasal cancer is consistent with a high-concentration effect of regenerative cell proliferation of the target organ coupled with the genotoxic effects of formaldehyde. Cell kinetic data from these studies provide important information that may be utilized in the assessment of risk for humans exposed to formaldehyde.
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    New technology, work and employment 5 (1990), S. 0 
    ISSN: 1468-005X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Sociology , Economics
    Notes: Great claims have been made about the growth prospects of the telematics sector, the primary source of communications networks and services. However, this article argues that the telematics sector faces some formidable barriers to growth, especially with respect to skills provision.
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Monoclonal antibody blocking studies reveal the involvement of three molecular pathways that mediate adhesion of resting human peripheral CD4^ T cells to IL-1-induced cultured human umbilical-vein endothelial cells (HUVEC). Antibodies specific for both the LFA-1 integrin and the inducible ...
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  • 10
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The nasal epithelium is an important target site for chemically induced toxicity and carcinogenicity. Gene expression data are being used increasingly in studies of such conditions. In order to provide normal baseline data for this target organ, we investigated gene expression profiles in nasal ...
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