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  • 1
    Electronic Resource
    Electronic Resource
    Recognition of human minor alloantigen(s) by cytotoxic lymphocytes in vitro (1982)
    Springer
    Immunogenetics 15 (1982), S. 485-499 
    Details
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Lymphocytes from an extensively transfused patient with aplastic anemia were induced to cytotoxicity against target cells from several HLA-matched siblings by in vitro stimulation with allogeneic cells. Effective stimulating cells shared HLA-B7 with the patient, but not all B7 individuals were effective. An additional factor, which was found to segregate in both the patient's and an unrelated sibship, was also necessary. Segregation of this minor alloantigen, W, was also revealed among the patient's HLA-matched sibs by differential susceptibility to lysis by effectors from the patient. The ratio of six positive to four negative siblings suggests that the antigen difference might be coded by a single locus. Lymphocytes from a normal sib, who like the patient is lacking the minor antigen, could not be induced to cytotoxicity against positive targets. Thus in vivo sensitization of the donor of the responding cells appears to be necessary for the demonstration of the cytotoxic response to the minor antigen in vitro. No correlation was observed between the segregation pattern of W and of known blood group antigens, and no cytotoxic antibody to W was detected in the patient's serum in several trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00345908
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  • 2
    Electronic Resource
    Electronic Resource
    Rate of potassium-sodium exchange by human lymphocytes: Prediction of the cooperative adsorption model (1979)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 98 (1979), S. 107-112 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The equilibrium parameters of potassium-sodium distribution in human lymphocytes, determined experimentally in the preceding study (Negendank and Shaller, '79), were incorporated into a stochastic treatment of the cooperative adsorption model in order to predict the kinetics of “active” potassium-sodium exchange. The rate of uptake of potassium, in potassium-depleted, sodium-loaded cells, is complex and deviates markedly from simple exponential functions. The sigmoid form of the exchange data closely followed the predicted curve. This result enhances one's confidence in the usefulness and applicability of the cooperative adsorption model, and adds further support to the association-induction hypothesis as a coherent theory of cell physiology.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1040980112
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  • 3
    Electronic Resource
    Electronic Resource
    Fast and slow fractions of K+ flux in human lymphocytes (1979)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 98 (1979), S. 539-552 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Potassium influx and efflux were studied in human peripheral blood lymphocytes equilibrated over a wide range of external K+ levels. The absence of a net ion movement throughout the flux study was established, trapped space was measured with polyethylene glycol, and cells were separated from incubation media without exposure to any washing solution. There are both rapid and slow cellular fractions of 42K influx and efflux, with half-times of exchange of around 2 minutes, and 400 minutes, respectively. The rapid component is identical in magnitude to the smaller non-saturable component of cell K+, while the slow component is identified with the larger, sigmoidal, saturable component of cell K+ that was previously shown to follow a cooperative adsorption isotherm. These results support the association-induction hypothesis, which predicts (a) a rapid fraction of K+ flux due to equilibration of ion within cell water existing in a state of polarized multilayers, and (b) a slower component of K+ flux limited by adsorption onto, or desorption from, fixed anionic sites existing throughout the cell. K+ influx, as a function of external K+, showed a triphasic relation with a peak around 1 mM K+ex, then a trough around 4 mM K+ex, and then a gradual rise. This relation was readily explained, in terms of the association-induction hypothesis, by the cooperative interaction between, and ion occupancy of, fixed anionic sites that absorb K+ or Na+.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1040980312
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  • 4
    Electronic Resource
    Electronic Resource
    Multiple fractions of sodium exchange in human lymphocytes (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 104 (1980), S. 443-459 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Human lymphocytes contain a large, saturable fraction of K+ that exchanges slowly with K+ in the external medium, and a small non-saturable fraction that exchanges rapidly. We determined whether or not Na+ exchanges in a similar manner with external Na+. Cells were pre-equilibrated to ensure absence of net ion movements. Efflux was studied by loading with 22Na and transferring without washing to a non-labeled medium. Influx was studied by transferring to labeled medium and separating large samples of cells at 6,000g. There are fast, intermediate, and slow fractions of Na+ exchange, with half-times of 2, 14, and 120 minutes. At normal external K+, most cell Na+ exchanges rapidly, while at lower external K+ the Na+ that replaces cell K+ exchanges slowly. Parallel sources of fast and slow fractions, such as extracellular ones and subpopulations of cells, were ruled out by simultaneous 42K and 22Na fluxes and by a quantitative analysis of the combined K+ and Na+ content and flux data over a range of external K+ and Na+ levels. Five possible models of ion fluxes occurring in series were considered. Surface matrix, surface binding sites, and cytoplasmic channels with rapid nuclea exchange were eliminated as sources of the fast fractions. Therefore, the fast fractions of K+ and Na+ must reflect the permeability of the surface membrane. This left only two possible sources of the slow fractions. One, a subcellular compartment (e.g., nucleus), was eliminated by the combined content and flux data. We conclude that the slow fractions of ion flux are rate-limited by adsorption onto and desorption from cellular macromolecules. The data support the association-induction hypothesis and are understood by reference to two fundamental concepts: that of rapid solute exclusion from cell water existing in a polarized state; and that of solute accumulation limited by adsorption onto fixed anionic sites within the cell.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041040317
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  • 5
    Electronic Resource
    Electronic Resource
    A critical temperature transition of K+-Na+ exchange in human lymphocytes (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 103 (1980), S. 87-95 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Human lymphocytes were equilibrated for 48 hours at 5-6 mM K+ex over a range of temperatures between 0 and 37°C, and at 5°C over a range of external K+ levels between 0 and 32 mM. Cell K+ and Na+ contents are normal between 37 and 10′. Below 10′ there is a critical thermal transition in ion contents centering around 3°C. This and the steep sigmoidal isotherms of K+ and Na+ at 5°C confirm the cooperative nature of ion exchange. At 0′, cell K+ is maintained at a concentration that is seven to eight times that of the external medium. Isotopic K+ influx shows smaller, rapidly-exchanging, and larger, slowly-exchanging fractions. The latter, which correspond to the saturable, sigmoidal components of cell K+, are slowed by decreasing temperature. Although there is a critical temperature transition of K+-Na+ exchange, there is no corresponding transition for isotopic K+ exchange, which has an activation energy of 11.6 kcal/mole. The combined ion content and flux data are readily understood by reference to two major concepts of the association-induction hypothesis: that of rapid solute exclusion from cell water existing in a state of polarized multilayers, and that of solute accumulation limited by adsorption onto and desorption from fixed anionic sites that interact with one another in a critical, cooperative fashion.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041030113
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  • 6
    Electronic Resource
    Electronic Resource
    The effect of metabolic inhibition on lon contents and sodium exchange in human lymphocytes (1982)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 110 (1982), S. 291-299 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Lymphocytes depleted of ATP by incubation in iodoacetate (IAA) and nitrogen (N2) lost K and gained Na. Isotopic Na exchange showed a fast fraction and a slower exponential fraction, the latter conventionally assumed to reflect surface membrane properties. The gain of cell Na was not accounted for by a decrease in 22Na efflux in either the slow or the fast fraction. After 3-5 hours, Na efflux increased. These results led us to question the concept that normal cell ion levels are maintained by an ATPase pump and could not be explained by exchange diffusion, cotransport, countertransport, or other inherently dissipative mechanisms. The data are, on the other hand, consistent with the concept that cell ion contents are determined by their relative exclusion from cell water coupled with selective adsorption onto fixed macromolecular anionic sites within the cell. In this view, the IAA, N2-induced rise in cell Na is due to the occupancy of adsorption sites losing K, while the increased isotopic exchange is due to a decreased activation energy for ion-site interaction.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041100312
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  • 7
    Electronic Resource
    Electronic Resource
    Potassium-sodium distribution in human lymphocytes: Description by the association-induction hypothesis (1979)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 98 (1979), S. 95-105 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Human lymphocytes were equilibrated for 48 hours over a wide range of external potassium levels, and their contents of potassium, sodium, and water determined. As external potassium rose from zero, cell potassium rose steeply in a sigmoidal fashion, reached half-saturation at 0.4 mM external potassium, and then saturated at 129 mmoles/kg cells. The saturable cell potassium exchanged mole-for-mole with sodium. Analysis of the saturable components by a statistical-mechanical adsorption model demonstrated a cooperative interaction between sites determining equilibrium potassium-sodium distribution. Superimposed upon the saturable fraction of cell potassium was a smaller one that was non-saturable with increasing external potassium to at least 64 mM, and that, when expressed as mmoles/liter cell water, existed in a ratio to external potassium of 0.6. The results strongly support the association-induction hypothesis, which predicts a small non-saturable component of ions determined by exclusion from oriented cell water and a cooperative interaction between sites throughout the cell that associate with potassium or sodium.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1040980111
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  • 8
    Electronic Resource
    Electronic Resource
    The effects of temperature and ouabain on steady-state Na and K exchanges in human lymphocytes (1982)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 113 (1982), S. 440-454 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The temperature-dependence of steady-state exchanges of K and Na were determined under conditions in which cell viability, ATP, water, Ca, and Mg were not confounding variables. Steady-state ion contents are near-normal between 37° and 10° C, Below 10° C K is replaced by Na in a mole-for-mole fashion with significant net K retention and Na exclusion occurring even below 3°C. The rates of steady-state Kand Na exchanges have markedly different temperature-dependences; between 37° and 10° C, for example, that of K decreases markedly while that of Na remains near-normal, and there is no consistent correlation between the steady-state exchanges and the ionic contents. Ouabain increases steady-state Na flux at 37° C and induces a more marked temperature-dependence over the entire temperature range. This effect is not due simply to inhibition of some processes and unmasking others; it mirrors a pronounced effect of ouabain on the intrinsic properties of Na self-exchange. These results are compatible with a model based on two simple concepts: (1) partial ionic exclusion from cellular water that is ordered by interaction with proteins; and (2) ionic accumulation mediated by adsorption onto and desorption from fixed macromolecular anionic sites, the majority of which interact with one another in a cooperative fashion. In this view, the sharp temperature transition in the net replacement of K by Na below 10° C is due to a critical transition in the selectivity of the cooperatively interacting adsorption sites. The rates of steady-state self-exchanges of K and Na are determined by parameters of ion-site interaction, and the major set of ion-adsorbing sites that interact cooperatively have a steep thermal activation energy of ionic self-exchange. When they are in the K-preferring state above 10° C, exchange of K has a steep temperature-dependence. When they are in the Na-preferring state below 10° C, exchange of Na has a steep temperature-dependence. When these sites are forced into a Na-preferring state at all temperatures by treatment with ouabain, exchange of Na acquires a steep temperature-dependence over the entire temperature range 37° to 0° C.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041130313
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