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  • 11
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 51 (1993), S. 165-174 
    ISSN: 0730-2312
    Keywords: cell growth inhibitors ; nalidixic acid ; ciprofloxacin ; DNA gyrase ; topoisomerase ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The 4-quinolone antibiotics nalidixic acid and ciprofloxacin and potent inhibitors of the bacterial type II topoisomerase DNA gyrase. Treatment of mouse L1210 leukemia cells with these drugs resulted in a delayed inhibition of cell proliferation. Prior to inhibition of cell proliferation, there was a time-dependent decrease in the cellular content of mitochondrial DNA (mtDNA). The decrease in mtDNA was associated with a decrease in the rate of mitochondrial respiration and an increase in the concentration of lactate in the growth medium. Inhibition of cell proliferation by 4-quinolones was reversible upon drug washout. However, there was a 2- to 4-day lag before the growth rate returned to normal levels. This was preceeded by an increase in mtDNA content and mitochondrial respiration. These studies suggest that inhibition of mammalian cell proliferation by 4-quinolone drugs is related to the selective depletion of mtDNA. © 1993 Wiley-Liss, Inc.
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  • 12
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 237-254 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The oral apparatus of neonatal and juvenile golden hamsters was investigated by clearing and staining of whole crania, videotaping of behavior, and electromyography of several jaw muscles. Chewing developed during the first postnatal week and matured in the second; however, suckling was still the primary mode of feeding. Micromovements of the jaws occurred early when the osseous skeleton and joints developed. Macromovements correlated well with EMG records and were limited to jaw opening at birth. Muscles of the oral floor generated large bursts of activity during jaw opening and tongue protrusion from 0 days postnatal (dpn), when simple and stereotyped gaping was induced, until 14 dpn, when movements were spontaneous and not stereotyped nor inducible. However, adductor muscle activity was brief, low in amplitude, and primarily involved with jaw stabilization until 4 dpn, when these muscles became active during closing the jaws; closing activity increased in frequency and amplitude until the end of the second week. Development of frequent, coordinated macromovements of chewing was associated with the refinement of joint structure and dental occlusion and with the growth of the craniofacial skeleton. Jaw movements and associated EMG's correlated better with available data on development of neural circuitry than with that for musculoskeletal development.
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  • 13
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 70 (1967), S. 13-33 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Different species of viruses contain linear or circular DNA molecules. The circular molecules are either single-chained or circular duplexes. The linear molecules from various species are always duplex. However, they may be either unique or circularly permuted collections of sequences. All species of linear duplexes that can be successfully tested can be shown to be terminally repetitious. The two temperate phages that have been studied (λ and P22) are unique and permuted collections, respectively. Shortly after infection both of these molecules form closed helical rings (superhelices). Certain virulent phages show no evidence of superhelix formation. How unique and permuted collections are produced at maturation is a puzzle. In this respect, it is of interest that P22 is a generalized transducing phage, whereas λ is a specialized transducing one.
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  • 14
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 87 (1976), S. 53-62 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We have investigated the effects of 2,4,6-trinitrobenzene sulfonic acid (TNBS), an amino reactive reagent, on passive cation movements in Ehrlich ascites tumor cells. Incubation of tumor cells with TNBS (3 mM) results in a two phase association of TNBS with the cells. An initial, rapid phase, presumably at the level of the membrane, is independent of temperature, while the second phase increases linearly in time and is temperature dependent. Kinetic analyses of Na+ movements indicate that TNBS: (1) inhibits Na+ movement from a slowly exchanging cellular compartment, but is without effect on a more rapidly exchanging compartment; (2) does not alter net Na+ accumulation in transport-inhibited cells; and (3) is without effect on non-exchange Na+ efflux at 0°C. The actions of TNBS on K+ movements depend upon temperature and the continued presence of TNBS in the environment. At 22°C two minute exposure of the cells to TNBS leads to 77% inhibition of K+ efflux. With continued exposure to TNBS, the inhibition is only 42%. Reduction of the temperature to 0°C decreases K+ efflux in control cells by 82%. Two minute exposure to TNBS enhances K+ efflux by 50%, while continuous exposure increases it by 144%. These results suggest: (1) TNBS interacts with several classes of membrane sites which are involved with the regulation of passive cation movements; and (2) passive Na+ and K+ movements across the cell membrane proceed by different pathways.
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  • 15
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 106 (1981), S. 399-406 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effects of valinomycin (25 pM) on the membrane potential and on initial, passive Na+ and K+ movements have been determined in Ehrlich ascites tumor cells. The membrane potential of steady-state cells in a physiologic environment was - 23.2 mV. Addition of valinomycin induced a small, significant hyperpolarization (Vm = -29.6 mV) when averaged over the population tested. However, analyses of the response of individual cells to valinomycin showed two different potential effects: (1) the majority of cells hyperpolarized after treatment; but (2) a significant fraction depolarized when exposed to valinomycin. The Vm of steady-state cells incubated in saline with K+ at concentrations of 21 mM or 75 mM was - 21.4 mV and -22.0 mV, respectively. Addition of valinomycin to these cells was without effect on Vm, thus establishing the “null point” responses. Only for cells incubated in saline with a K+ of 75 mM was there agreement between Vm and K+ equilibrium potential (Vk). Determinations of cellular Na+ and K+ showed that valinomycin induced net losses of K+ and gains of Na+ by cells incubated in either physiologic saline or saline with a K+ concentration of 21 mM. However, the celular K+ of cells incubated in saline with a K+ concentration of 75 mM was unaltered by valinomycin. There was a two- to threefold increase in K+ permeability of the cell membrane in the presence of valinomycin. These results are consistent with the existence of two null points in the membrane-potential response to valinomycin: One is established when the membrane potential corresponds to Vk; the second occurs when the effects of valinomycin on K+ loss from the cell are exactly offset by its inhibition of active Na+ + K+ transport.
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  • 16
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 106 (1981), S. 407-418 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effects of altered external sodium and potassium concentrations on steady state, active Na+ + K+ transport in Ehrlich ascites tumor cells have been investigated. Membrane permeability to Na+ and K+, intracellular [Na+] and [K+], and membrane potential were measured. Active cation fluxes were calculated as equal and membrane potential were measured. Active cation fluxes were calculated as equal and opposite to the net, diffusional leak fluxes. Elevation of external K+ (6-60 Mm)by equivalent replacement of Na+ (154-91 mM) inhibits both active Na+ and K+ fluxes, but not proportionally. This results in a decrease of the coupling ratio (rp = -Jkp/JpNa) as external K+ is increased. Elevation of external K+ (3-68 mM) at constant Na+ (92mM) inbibits Jpk, but is without effect on JpNa. The coupling ratio declines from 1.01 ± 0.14 to 0.07 ± 0.05, a 14-fold alteration. Reduction of external Na+ (154-25 mM) at constant K+ (6mM) depresses JpNa, but is without effect on Jpk. The coupling ratio increases from 0.63 ± 0.04 at 154 mM Na+ to 4.5 ± 2.04 at 25 mM Na+. The results of this investigation are consistent with the independent regulation of active cation fluxes by the transported species. Kinetic analysis of the data indicates that elevation of external sodium stimulates active sodium efflux by interacting at “modifier sites” at the outer cell surface. Similarly, external potassium inhibits active potassium influx by interaction at separate modifier sites.
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  • 17
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 125 (1985), S. 499-506 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effects of heparin on the in vitro growth of rat cervical epithelial cells were examined. Heparin was found to inhbit in a dose dependent fashion the log-phase growth of rat cervical epithelial cells (RCEC) grown in the absence of medium supplements. An inhibition of growth is observed at concentrations as low as 500 ng/ml and 50% inhibition of growth occurs at a concentration of 5 μ/ml. The growth inhibitory activity of heparin is independent of anticoagulant activity since three separate non-anticoagulant preparations of heparin all inhibit growth. Other glycosaminoglycans including chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, hyaluronic acid, and keratin sulfate do not inhibit the growth of rat cervical epithelial cells. The ability of heparin to inhibit the log-phase growth of rat cervical epithelial cells is dependent on the composition of the medium in which the cells are grown. The addition of ≥ 7.5 ng/ml epidermal growth factor to epithelial cultures blocks the growth inhibitory activity of heparin. These results suggest that components of the extracellular matrix modulate the growth responses of epithelial cells and may be important in regulating cellular proliferation in normal and pathological states.
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  • 18
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 132 (1987), S. 255-262 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The glycosaminoglycan heparin inhibits the growth of a number of different cell types in vitro including smooth muscle cells, mesangial cells, fibroblasts, and rat cervical epithelial cells (RCEC). Studies investigating the antiproliferative effects of heparin on smooth muscle cells have demonstrated the site of the cell cycle block and revealed several metabolic alterations that could be causally associated with growth inhibition. We have investigated these metabolic parameters in RCEC to determine whether they are also associated with the antiproliferative effects of heparin in epithelial cells. Heparin acts rapidly to inhibit RCEC growth with inhibition detectable by autoradiography 7 h after the addition of heparin. Heparin treated RCEC begin to enter S-phase 12 h after the removal of heparin. These findings suggest that heparin blocks RCEC in the early-to-mid G1 phase of the cell cycle rather than late in G1 or early in S-phase as has previously been demonstrated for smooth muscle cells. Unlike smooth muscle cells, the uptake of thymidine and uridine is not inhibited by heparin in RCEC. Treatment of medium with heparin-Sepharose does not reduce the subsequent growth of RCEC; heparin inhibits the growth of RCEC in heparin-Sepharose treated medium in a manner identical to that in nontreated medium. Therefore the growth inhibitory effects of heparin cannot be explained by the inactivation of mitogens present in serum. In contrast to its effects on smooth muscle cells, heparin treatment of RCEC does not result in a reduction in the binding of epidermal growth factor (EGF) to the cells. These results indicate that although heparin inhibits the growth of a variety of cell types, significant differences exist in the responses of the different cells to heparin.
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  • 19
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 87 (1976), S. 47-52 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We have investigated the effects of La+3 binding to the surface of Ehrlich ascites tumor cells on cell electrophoretic mobility and passive movements of Na+ and K+. Incubation of tumor cells in La+3-containing media results in a La+3 concentration-dependent decrease in net surface charge negativity. At [La+3] greater than 0.5 mM, the net surface charge becomes positive with maximum positivity occurring at [La+3] = 0.9 mM. The effects of La+3 binding on passive Na+ and K+ movements were investigated by following 22Na and K+ losses from ouabain-inhibited cells. Neither low (0.02) nor high (1.0 mM) [La+3] had any effect on the K+ efflux rate coefficient. 22Na losses from control and La+3-treated cells were consistent with washouts from two cellular compartments. Low [La+3] (0.02 mM) was without effect on Na+ loss from the cells. However, higher [La+3] (1.0 mM) resulted in a 48% inhibition of Na+ loss from the more slowly exchanging compartment. These results are not consistent with simple electrostatic interactions exerting a major influence on the passive movements of Na+ and K+. It is suggested that La+3 interacts with sites specific for Na+, perhaps involved in a carrier-mediated exchange system.
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  • 20
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 115 (1983), S. 131-136 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Recent investigations have indicated that cellular rheogenic properties may interfere with the correct estimation of Na+ and amino transport stoichiometry. We have reevaluated the stoichiometry of Na+ and α-aminoisobutyric acid (α-AIB) cotransport in Ehrlich ascites tumor cells depleted of Na+ and ATP by incubation in Na+ -free HEPES-buffered medium (pH 7.2) containing 160 mM K+ and 2.5 μM valinomycin. Transfer of the cells to a medium with 10 mM 22Na+, 10 mM 3H-AIB, and 150 mM K+ resulted in an enhancement of Na+ flux above basal levels, which represents 0.6 of the AIB uptake. Under these conditions the membrane potential, -7.0 ± 0.1 mV (SEM), does not change with the addition of AIB, -7.3 ± 0.6 mV (SEM). HgCl2 (10 m̈M) added to the medium inhibited AIB flux and AIB-stimulated Na+ flux by 45-50% but did not change the coupling ratio. HgCl2 (10 m̈M) does not inhibit the basal Na+ flux nor does it affect cellular Na+ or K+ content. In physiological medium cotransport is electrogenic. The membrane potential of Ehrlich cells in physiological medium is -22.3 ± 0.8 mV (SEM) and depolarizes to -16.7 ± 0.7 mV (SEM) upon addition of AIB. Under these conditions the coupling ratio was highly variable but the ratio of codepression is 0.90 ± 0.02 (SEM) in the presence of HgCl2 (10 m̈M). These results are consistent with a model (Smith and Robinson, 1981) in which the stoichiometry is one cosubstrate molecule per molecule of α-AIB. We suggest that H+ provides the alternative cosubstrate in this low Na+ environment and that in high Na+ medium the Na+ :AIB stoichiometry approaches 1:1.
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