[Blood digitalis curves in the aged].
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Biomedical subjects
Publications and source records attributed to S Lin.
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The effect of diphenylhydantoin (DPH) has been studied on certain membrane properties of the crayfish stretch receptor neuron (SRN) and of neurons in the abdominal and buccal ganglia of Aplysia. DPH decreases the amplitude of post-tetanic hyperpolarization of the SRN, which is thought to be an expression of the electrogenic pump, and does not antagonize the effect of ouabain on this activity. DPH decreases the membrane resistance of all the different types of neurons studied, with little or no change in the resting membrane potential. It decreases the overshoot of the action potential in some of the neurons studied and prolongs the falling phase and the undershoot in other neurons. DPH also decreases repetitive firing. These effects have also been observed at different external concentrations of potassium. It is concluded that DPH, in the different preparations studied, does not have any effect on or decreases the electrogenic pump, but produces changes in other membrane properties which are consistent with its anticonvulsant action.
The effect of diphenylhydantoin (DPH) on certain synapses of neurons in the abdominal ganglion of Aplysia and on the gamma-aminobutyric acid (GABA) mediated inhibitory synapse of the crayfish stretch receptor neuron (SRN) has been studied. DPH decreases the amplitude of the excitatory postsynaptic potential, but is ineffective on the "short" ACh mediated, Cl- dependent, inhibitory postsynaptic potential (IPSP) in Aplysia. However, it facilitates the "long" ACh mediated, K+ dependent, IPSP, in this same group of neurons. DHP has a profound effect on the GABA mediated, Cl- dependent, inhibitory synapse of the SRN. The time course of the IPSP is prolonged up to 10 times control values, due to an increased and prolonged postsynaptic conductance. Similar results have been obtained in the SRN with iontophoretic application of GABA. This selective effect of DPH on synaptic mechanisms, especially in view of the role of GABA and ACh as putative transmitters in the mammalian nervous system, may play an important role for the anticonvulsant action of DPH.
Contemporary analytical systems based on mass spectrometry include as components a gas chromatograph, a mass spectrometer, and a computer. The form of operation is usually in electron impact ionization mode for identification and structural studies, and in chemical ionization mode for quantitative analyses. Important stages in the development of these systems included the design of "molecule separators" for the concentration of solutes in the gas phase, the use of mass spectrometers as specific ion detectors, the introduction of chemical ionization techniques, and the development of computer-based operation, data acquisition, and data analysis capabilities. A current line of investigation is concerned with the design and use of systems based on atmospheric pressure ionization. Samples are ionized in a small reaction chamber external to the low-pressure region of a quadrupole mass analyzer. The primary source of electrons is a 63Ni foil or a corona discharge. The ionization process leading to positive ions involves a sequence of ion molecule reactions, usually electrons leads to carrier gas ions leads to reagent ions leads to sample component ions. Negative ions may be formed by direct electron attachment, or by ion molecule reactions that include new types of elimination reactions. The source will accept a variety of gases and solvents. The sample may be introduced in the gas phase without solvents, by probe injection, or in the effluent stream from a gas chromatograph. Samples may be introduced in the liquid phase in solvents by injection after the fashion of gas chromatography or in the effluent stream from a high-performance liquid chromatograph. The novel aspects of atmospheric pressure ionization mass spectrometry lie in its versatility and high sensitivity of detection. Few clinical chemistry laboratories now use these systems. Significant future uses are likely to be in analytical work involving therapeutic drug monitoring and studies of drug metabolism, and in analyses for environmental biohazards including pesticides, herbicides, polyhalobiphenyls, dibenzodioxins, and other toxic compounds.
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To study the molecular basis of changes in sugar uptake rate in cultured mouse fibroblasts with different physiological states, we have measured the high affinity binding of [3H] cytochalsin B, a potent sugar transport inhibitor, to actively growing and contact inhibited Balb/3T3 cells as well as to 3T12 and SV3T3 cells. Binding was the same whether the cells were detached from dishes with EDTA or trypsin. The amount of drug bound to intact cells measured with a centrifugation assay was essentially the same as that bound to cell sonicates measured with equilibrium dialysis. Cytochalasin B binding to intact cells was extremely rapid and reversible over a wide range of drug concentrations, and was not affected by 0.1 M D--glucose in the assay medium. Actively growing and contact inhibited 3T3 cells had a similar number of high affinity cytochalasin B binding sites per cell, while 3T12 and SV3T3 cells had one third to one fourth the number of sites per cell. However, the number of sites per mug cellular protein appeared to be similar for cells in all of the physiological states examined.
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Using a membrane filter assay, we have obtained results from both kinetic and competition experiments indicating that histones bind more strongly to bromodeoxyuridine-substituted DNA than to normal DNA. At 37 degrees C in our standard buffer of 0.2 M ionic strength, the rate of dissociation of histones H1, H2, and h4 from BrdU-substituted DNA is respectively 7, 4, and 2 times slower than it is from normal DNA. Competition experiments show an even greater difference between BrdU-substituted and normal DNA with respect to histone binding. The tighter binding of histones to BrdU-substituted DNA is of interest because of the known effects of BrdU on eukaryotic chromosome condensation and staining, virus induction, and the inhibition of differentiation.
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By equilibrium competition experiments, the dissociation constant (K(RD)) of lac repressor for E. coli DNA carrying a deletion of the lac operon was measured at a variety of salt concentrations. These data are used in the consideration of several aspects of protein-DNA interaction: Quantitative estimates of specificity are made. Specificity changes only slightly with salt concentration. We calculate that in vivo, 98 percent or more of repressor is bound to DNA predominately at sites other than the lac operator. Inducers shift repressor from operator to nonoperator DNA, but do not free it from DNA. The general affinity of repressor for E. coli DNA is sufficient to support a model where repressor slides along DNA for significant distances. The effective dissociation constant of repressor for operator (K(eff)) is very sensitive to the total DNA concentration. We propose that "junk" DNA in eucaryotes functions to maintain total DNA at an optimum concentration. We consider the lac operon in the nucleus of a lymphocyte, point out that severe difficulties would be encountered, and suggest possible solutions.
Recently developed scanning electron microscopes provide sufficient resolution to allow useful observation of subcellular biological objects. Preparation methods for such objects need not be limited to the traditional coating and mounting procedures. Many methods developed for transmission electron microscopy are immediately adaptable to scanning electron microscopy. We show that a number of techniques are available to the microscopist which yield adequate contrast and high resolution. As examples we show skeletal muscle myofibrils dispersed to reveal thick filaments, uncoated on a thin carbon film; a tropomyosin tactoid, negatively stained with uranyl acetate; oncornavirus, conventionally coated; and T4 bacteriophage on an aluminium substrate.
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The authors used radioimmunity to study blood digoxin behaviour in patients with normal renal function and with variable BUN. The computerized and mathematically considered data showed that digitalic intoxication occurs with higher digoxin blood levels in patients with renal failure than in normal renal function cases. In the first case, moreover, it occurs sooner than in the second one, and the total digoxin dose is smaller than in normal patients. We have found that the large range of digosin blood levels is vital in deciding the therapeutic and toxic dose; that may be done, for most cases, following the estimate of the theoretical saturation dose using our method.
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