Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alkylating agents have caused acute nonlymphocytic leukemia (ANLL), probably bladder cancer, and possibly other solid tumors. Phenacetin also has enhanced risk of bladder cancer, and probably also carcinoma of the renal pelvis. Topical nitrogen mustard, potassium arsenite, tar ointments, and methoxsalene have been related to development of nonmelanotic skin cancers. Immunosuppression by azathioprine, usually with prednisone, has enhanced risks of non-Hodgkin's lymphomas, hepatobiliary cancers, and various mesenchymal tumors. Liver cancers have been reported in users of androgenic anabolic steroids, and both hepatic cell adenomas and carcinomas have been associated with use of combined oral contraceptives. These contraceptives reduce risks of endometrial and ovarian carcinomas. Estrogens increase risk of endometrial cancer. Exposure to diethylstilbestrol in utero can result in clear cell carcinomas of the vagina and cervix, and possibly testicular carcinomas.
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PMID:Steroid hormones and medications that alter cancer risks. 304 37

In many excitable cells, there is a time after the action potential when the threshold for eliciting a second action potential is lower than it is in the steady state. The Hodgkin and Huxley (1952) equations predict such a supernormal period. Using their model, it is shown that the supernormal period results from the slow kinetics of the potassium current and does not depend on sodium current activation or inactivation or on the after-depolarization.
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PMID:Etiology of the supernormal period. 324 28

In a train of impulses in squid giant axon, accumulation of extracellular potassium causes successive afterhyperpolarizations to be progressively less negative. In Loligo, Frankenhaeuser and Hodgkin had satisfactorily accounted for the characteristics of this effect with a model in which the axon is surrounded by a space, width theta, and a barrier of permeability P. In axons isolated from Alloteuthis, we found that the model fitted the observations quite well. Superfusing the axon with hypotonic artificial seawater (ASW) caused theta and P to decrease, and, conversely, hypertonic ASW caused them to increase: this would be the case if both the space and the pathway through the barrier were extracellular. In some cases, in normal ASW, the afterhyperpolarizations in a train decreased very little, less than 0.7 mV. In these extreme cases, theta was estimated to be 190 nm and P to be 7 x 10(-4) cm s-1, both several times the values of 30 nm and 6 x 10(-5) cm s-1 estimated by Frankenhaeuser and Hodgkin. We suggest that in vivo the periaxonal space may be considerably wider than that seen in conventionally fixed squid tissue.
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PMID:K+ accumulation in the space between giant axon and Schwann cell in the squid Alloteuthis. Effects of changes in osmolarity. 334 36

We investigated the ionic interactions responsible for the characteristic nonrepetitive spike activity of amacrine cells. First we measured 4 pharmacologically separable ionic components: a voltage-gated, transient inward sodium current, a voltage-gated, sustained inward calcium current, a calcium-gated, sustained outward potassium current, and a voltage-gated, transient outward potassium current. The measurements provided the time course and magnitudes of the underlying conductances as functions of voltage. Each current was simulated following conventional Hodgkin-Huxley theory. A composite of the simulated currents was analytically reassembled to generate an approximation of the voltage response to a current step. By artificially varying the magnitude and kinetics of the different conductances in the simulation, we determined the range of values that supported the nonrepetitive spike-like response. Amacrine cells tend to remain refractory following an initial spike because (1) the entire activation range for potassium is located at positive potentials with respect to sodium inactivation, so sodium inactivation is never fully extinguished, and (2) the fully activated sodium conductance is of insufficient magnitude to subsequently reach threshold, given this residual inactivation. Shifting the sodium inactivation range by 10 mV, or increasing sodium conductance by 5 times, leads to a more repetitive form of activity. Changes in the magnitude, time course, or activation range of the potassium conductance cannot alter these conditions.
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PMID:The interaction of ionic currents mediating single spike activity in retinal amacrine cells of the tiger salamander. 368 3

We have analyzed the combined utilization of highly permeant anions to induce membrane diffusion potentials and glucose uptake to probe the created potentials as a new approach to quantitative generation and estimation of membrane potential differences in vesicle studies. Rabbit jejunal brush-border membrane vesicles were used in our experiments so that membrane potential differences can be calculated from the Goldman-Hodgkin-Katz equation with the relative ion permeabilities recently reported for this preparation (Gunther, R.D., Schell, R.E. and Wright, E.M. (1984) J. Membrane Biol. 78, 119-127) or approximated by the Nernst potential for the anion. Iodide was selected as the highly permeant anion after showing its absence of effect on glucose uptake with equal concentrations of Na+ inside and outside the vesicles and the membrane potential clamped to zero with gramicidin D. Membrane potential was varied by altering the intra- and extravesicular iodide concentrations while keeping isosmolarity and isotonicity constant by chloride replacement. In these conditions, glucose uptake was sensitive and correlated to the expected membrane potentials. Moreover, a linear relationship between the log initial rate of glucose transport and membrane potential differences could be established. This linear relationship was quite insensitive to inside replacement of choline by potassium and to pH variations in the incubation medium, thus showing the reproducibility and the versatility of the method and the adequacy of glucose uptake as a probe for membrane potentials. However, no information can be gained on the stoichiometry of the Na+-glucose transporter as the slope of the straight line depends on both the charge carried by the fully loaded carrier and the point in the electric field at which the transition state of the carrier from cis to trans occurs. This new approach was compared with the more conventional one using valinomycin-induced K+-diffusion potentials and the Nernst potential for potassium as means for creating and estimating membrane potential differences. Both techniques were not equivalent, as linear relationships showing smaller slopes and sensitivity to pH were recorded with the latter. These differences are compatible with a potassium permeability in the presence of valinomycin that is lower than generally assumed, at least when compared to the permeability of the other ions present in the incubation medium.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Highly permeant anions and glucose uptake as an alternative for quantitative generation and estimation of membrane potential differences in brush-border membrane vesicles. 370 49

A number of small organic molecules with general anaesthetic action have been examined for their effects on the voltage-dependent potassium current of the squid giant axon. They include representatives of the three classes of anaesthetics examined in previous studies on the sodium current (Haydon & Urban, 1983a, b, c), i.e. the non-polar molecules n-pentane, cyclopentane and CCl4, several n-alkanols and the inhalation anaesthetics chloroform, halothane, diethyl ether and methoxyflurane. Potassium currents under voltage clamp were recorded in intact and in intracellularly perfused axons before, during and after exposure to the test substances, and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the curves of the steady-state activation against membrane potential and reductions in the potassium conductance at 60 or 70 mV membrane potential have been tabulated. On the same intact axons, all the anaesthetics with the exception of methoxyflurane reduced potassium currents less than sodium currents by about a factor of two or more. For the n-alkanols, butanol to decanol, the concentrations required to reduce the potassium current at 60 mV membrane potential by 50% were determined. For n-butanol to n-heptanol, the standard free energy per CH2 for adsorption to the site of action was estimated to be -2.91 kJ mol-1 as compared with -3.04 kJ mol-1 for reduction of the sodium current. The magnitude of the free energy decreased for alkanols with longer chain lengths. At anaesthetic concentrations that reduce the sodium current by 50%, the hydrophobic substances n-pentane and cyclopentane reduced the maximal sodium conductance, gNa, and the potassium conductance at 70 mV, gK70, equally by about a third, while the n-alkanols reduced both parameters by less than 10%. By contrast, diethyl ether and methoxyflurane were more effective in reducing the maximal potassium conductance. All of the test substances examined, except n-pentane and n-hexane, shifted the voltage dependence of the potassium steady-state activation in the depolarizing direction. A broad qualitative correlation was found between the shifts in the activation curves for sodium and potassium currents but, quantitatively, the agreement between the two shifts was poor. In n-decanol and methoxyflurane solutions, the voltage-clamped potassium currents exhibited pronounced inactivation-like behaviour. These currents can be fitted by the Hodgkin-Huxley formalism if an inactivation term analogous to the sodium current inactivation is added.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The actions of some general anaesthetics on the potassium current of the squid giant axon. 374 76

We have studied periodic as well as aperiodic behavior in the self-sustained oscillations exhibited by the Hodgkin-Huxley type model of Chay, T. R., and J. Keizer (Biophys. J., 1983, 42:181-190) for the pancreatic beta-cell. Numerical solutions reveal a variety of patterns as the glucose-dependent parameter kCa is varied. These include regimes of periodic beating (continuous spiking) and bursting modes and, in the transition between these modes, aperiodic responses. Such aperiodic behavior for a nonrandom system has been called deterministic chaos and is characterized by distinguishing features found in previous studies of chaos in nonbiophysical systems and here identified for an (endogenously active) excitable membrane model. To parallel the successful analysis of chaos in other physical/chemical contexts we introduce a simplified, but quantitative, one-variable, discrete-time representation of the dynamics. It describes the evolution of intracellular calcium (which activates a potassium conductance) from one spike upstroke to the next and exhibits the various modes of behavior.
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PMID:Bursting, beating, and chaos in an excitable membrane model. 388 58

The validity of the membrane hypothesis of aging (Zs.-Nagy, 1978) was tested on identified giant neurons of the snail Lymnaea stagnalis L. by using a combination of intracellular microelectrophysiology and X-ray microanalysis of the intracellular water and electrolyte concentrations on the very same cells. The snails were taken from an inbred stock and divided into young, adult and old age groups (3, 12 and 24 mth, respectively). The giant neuron called LPa-2 from the left parietal ganglion was selected for the studies. The resting potential of the cell membrane was recorded by means of intracellular microelectrode technique. The very same cells were then explored by freeze fracture and analyzed by an energy dispersive bulk specimen method of X-ray microanalysis. The resting membrane potential displayed an age-dependent hyperpolarization, the intracellular water content decreased considerably and the intracellular potassium concentration increased almost 90% by old age. The relative passive permeability ratio for potassium (PK) and chloride (PCl) was calculated from the measured data by means of the Goldman-Hodgkin-Katz equation. Such calculations revealed that PK decreases nearly 50% with age causing the increase of the intracellular potassium content, and this is accompanied also by a significant decrease of the PCl. The results support the validity of the membrane hypothesis of aging and are in agreement with the general knowledge regarding the electrophysiological behaviour of the giant neurons of Gastropode snails.
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PMID:Verification of the membrane hypothesis of aging on the identified giant neurons of the snail Lymnaea stagnalis L. (Gastropoda, Pulmonata) by a combined application of intracellular electrophysiology and X-ray microanalysis. 400 10

A physically based theory of ionic currents associated with nervous activity is extended to provide a model of electrical activity in the cortex and its immediate neighbourhood. It is shown that the most significant variations of potential in the extracellular fluid are associated with fluctuations in density of calcium and potassium ions. Nervous activity may activate a calcium resonance at the external surface of a neural membrane, which in turn excites a potassium resonance. The resulting variations of electrical potential are sufficient to account for the event related potentials observed in the extracellular fluid. In addition, it is found that periodic variations of potential associated with the potassium resonance may be initiated by metabolic changes in ion concentrations and are in close correspondence with those identified experimentally with the alpha- and beta-rhythms. It is shown how to determine the effective conductance of the neural membrane from ionic theory, with a result comparable to that assumed by Hodgkin & Huxley, under the conditions of the voltage clamp.
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PMID:Extracellular fields within the cortex. 403 63

Alamethicin is an antibiotic which produces voltage gated channels in lipid bilayer membranes. Recently completed studies of the pressure dependence of alamethicin conductance have shown that its onset following application of a suprathreshold voltage step at a pressure of 100 MPa (1000 atm) is markedly slowed relative to that observed at ambient pressure. Furthermore, the time course of the onset of conductance becomes distinctly sigmoidal at elevated pressure, a condition which is not evident at atmospheric pressure. The decay of alamethicin conductance upon removal of suprathreshold applied voltage is also slowed by application of hydrostatic pressure, but it follows a single exponential time course at all pressures. In addition, kinetic parameters characterizing the onset and decay of conductance show distinctly different pressure dependences. These observations cannot be explained by a two state model in which alamethicin moves reversibly between nonconducting and conducting states. Therefore we re-examine critically a hypothesis made by previous workers, namely that alamethicin, in monomeric or aggregate form, moves upon application of suprathreshold voltage first from a nonconducting surface state to a nonconducting preassembly or precursor state, and then finally into a conducting state. Parameters of this three state model are related to a geometric factor which measures the degree of sigmoidal conductance response and which can be evaluated directly from experimental data. An alternative aggregation-type analysis, equivalent to that applied by Hodgkin & Huxley to the potassium conductance in squid axon, is also considered in the context of this same geometric factor. The possibility of distinguishing between these analyses on the basis of experimental data is discussed.
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PMID:A three state model for alamethicin conductance in bilayer membranes. 407 49


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