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Biomedical subjects

N E Williams

Publications and source records attributed to N E Williams.

At least 73 records · Page 4Linked to original sources
PubMed1979

Pharmacokinetics and pharmacological effects of neostigmine in man.

1 The pharmacokinetics of neostigmine was studied in six patients during the reversal of neuromuscular block induced by tubocurarine chloride. The effect of the drug on neuromuscular function was simultaneously assessed by electromyography. 2 Neostigmine was rapidly eliminated from plasma after intravenous administration. The decline in the plasma concentration of the drug was invariably resolved into two exponential components. The fast disposition (distribution) half-life of the drug was invariably less than 1 min; the slow disposition (elimination) half-life ranged from 15.4--31.7 min. 3 Neostigmine usually increased the amplitude of the compound muscle action potential and diminished electromyographic decrement within 2 min of intravenous injection. The pharmacological effect of neostigmine was usually maximal between 7 and 15 min. There was an inverse relationship between the plasma concentration of the drug and the facilitation of neuromuscular transmission. 4 Red cell acetylcholinesterase activity was almost completely inhibited within 2--3 min of intravenous injection of neostigmine. Enzyme activity recovered to approximately 28% of control values by 30 min and to 55% by 60 min.

Acetylcholinesterase↗
PubMed1978

Clearance of neostigmine from the circulation during the antagonism of neuromuscular block.

The plasma concentration of neostigmine was measured in five patients during the antagonism of neuromuscular block. The concentration of the drug decreased rapidly between 2 and 5 min after administration, and then more slowly. Detectable concentrations of neostigmine were present in plasma after 60 min. In the five patients the distribution half-life of neostigmine was less than 1 min; the elimination half-life ranged from 15.4 to 30.1 min.

Adult↗
PubMed1977

Inter-strain variability of structural proteins in Tetrahymena.

The high molecular weight proteins found in isolated pellicles of Tetrahymena have been compared in several individual strains within the genus using SDS polyacrylamide gel electrophoresis. Three variants of the beta-protein of epiplasm (MW 174,000; 155,000; 145,00) and 2 of the C-protein (MW 140,000; 122,000) were found among the strains examined. No variation was observed in the major kinetodesmal fiber protein (MW 250,000). The variation found between strains in the proteins of a structure which is (as far as we know) the same in all strains indicates a disjunction between evolutionary change at the 2 levels of organization. The taxonomic implications of the observed variation in structural proteins in Tetrahymena are discussed.

Animals↗
PubMed1977

Biochemical approaches to problems of cellular patterning.

The expression of intracellular patterning is perhaps nowhere more impressive than in the arrangements of structural elements associated with the cell surface in protozoa. The view is proposed that biochemical studies of protozoan plasma membranes and associated surface structures represent important contributions of potential significance for the understanding of the perpetuation and expression of positional information at the intracellular level. Some recent work dealing with the isolation, identification, and metabolism of pellicular proteins in Tetrahymena is presented and discussed. Some integral membrane proteins have been identified by iodination and polyacrylamide gel electrophoresis. Labeling studies suggest heterogeneous turnover rates within the group of presently identified membrane proteins. High molecular weight proteins with some similarity to spectrin have been isolated from Tetrahymena epiplasm. It is suggested that the ciliate epiplasm is one example of membrane-associated, actomyosin-like systems found in a variety of cell types. The epiplasm may play a role in the positioning of surface-associated structures and in the control of cell shape.

Animals↗
PubMed1976

A quantitative gas-liquid chromatographic method for the determination of neostigmine and pyridostigmine in human plasma.

A sensitive and selective analytical method was used to measure the concentration of neostigmine and pyridostigmine in human plasma. The procedure involved preliminary ion-pair extraction of the drugs into dichloromethane, followed by concentration and anlysis of the ion-pair complex using a gas-liquid chromatographic system fitted with a nitrogen detector. Using the peak area ratio technique, pyridostigmine bromide was used as the internal standard for the quantitation of neostigmine in plasma; neostigmine bromide was the internal marker for the determination of pyridostigmine. The method depends on the thermal dequaternisation of the quaternary amines, and can be used to detect 5 ng/ml in a 3-ml plasma sample. Accurate measurement can be made at levels of 50-1000 ng/ml. This assay procedure has been applied to the separate determination of the plasma concentration of neostigmine and pyridostigmine after single administration of intravenous doses in aneasthetised patients.

Chromatography, Gas↗
PubMed1976

Plasma concentration of edrophonium in man.

The plasma concentration of edrophonium was measured in man after intravenous administration. In 5 patients, the clearance of edrophonium from the circulation during the 1-hr period of sampling was invariably resolved into 2 exponential components. An initial rapid phase of elimination from plasma (T/2 = 0.54 TO 1.92 Min) was followed by a much slower decline (T/2 = 24.23 to 45.00 Min), corresponding to the fall in concentration between 10 and 60 min. In parallel experiments in the rat, the clearance of 14C-edrophonium was resolved into 3 exponential components, although the final component could not be reliably defined until 1 to 3 hr after intravenous injection. It is suggested that the rapid fall in the plasma concentration of edrophonium in both species is not dependent on metabolism or excretion, but is due to the rapid uptake of the drug by the liver and kidneys.

Acetylcholinesterase↗
PubMed1976

Macronuclear division with and without microtubules in Tetrahymena.

The effects of cold shocks (0 degrees C) and colchicine (4 mg/ml) on macronuclear microtubules and macronuclear division have been investigated in Tetrahymena. Macronuclear division was affected by both treatments, but loss of microtubules occurred only in the presence of colchicine. When colchicine was applied immediately prior to macronuclear elongation, the nuclei underwent a partial elongation without microtubules, but were unable to constrict and separate into daughter nuclei. Such nuclei were cut in two by the advancing cytoplasmic fission furrow. When colchicine was applied to macronuclei in the fully elongated state, that maintained their elongation in the absence of microtubules, and were subsequently separated into daughter nuclei by the cytoplasmic furrow. It is suggested that macronuclear microtubules, most probably the membrane-associated microtubules, are required for the terminal stages of nuclear elongation and separation. However, the considerable macronuclear elongation which takes place in the absence of microtubules serves to focus attention on molecular mechanisms of force production which must reside elsewhere in the macronucleus.

Animals↗
PubMed1973

Regulation of microtubules in Tetrahymena. I. Electron microscopy of oral replacement.

The coupled resorption and redifferentiation of oral structures which occurs in Tetrahymena pyriformis under conditions of amino acid deprivation has been studied by transmission electron microscopy. Two patterns of ciliary resorption have been found, (a) in situ, and (b) after withdrawal into the cytoplasm. No autophagic vacuoles containing cilia or ciliary axonemes have been seen. Stomatogenic field basal bodies arise by a process of rapid sequential nucleation, with new ones always appearing next to more mature ones, even though the latter may not be fully differentiated. Accessory radial ribbons of microtubules develop immediately adjacent to oral field basal bodies as a late step in their maturation. It can be seen that the formation of basal bodies and their orientation within the oral complex are separate processes. This is true for about 130 of the approximately 170 oral basal bodies; the remaining 40 or so form within the patterned groups of ciliary units as a later event. Clusters of randomly oriented thin-walled microtubules are found surrounding oral basal bodies at all times during stomatogenesis. They may either represent stores of microtubule subunit protein, or serve as effectors of basal body movement during their orientation into pattern.

Animals↗
PubMed1973

Regulation of microtubules in Tetrahymena. II. Relation between turnover of microtubule proteins and microtubule dissociation and assembly during oral replacement.

Experiments are reported which were designed to test for induced synthesis of microtubule proteins associated with the rapid proliferation of basal bodies and associated intracytoplasmic microtubules which occurs during oral replacement in Tetrahymena. None was found. Instead, it is shown that these structures can be formed with de novo synthesis of as little as 6% of their microtubule proteins. It is suggested that basal body proliferation may be controlled by synthesis of morphogenetic regulator proteins.

Animals↗
PubMed1971

The synthesis of microtubule and other proteins of the oral apparatus in Tetrahymena pyriformis.

Several proteins, including microtubule proteins, have been isolated from the oral apparatus of the ciliate Tetrahymena. The synthesis of these proteins has been studied in relation to formation of this organelle system by the cell. Electron microscopy has shown that the isolated oral apparatus consists primarily of basal bodies, pellicular membranes, and a system of subpellicular microtubules and filaments. Cilia were removed during the isolation; therefore none of the proteins studied was from these structures. Evidence was obtained from the study of total oral apparatus protein which indicates that at least some of the proteins involved in formation of this organelle system may be synthesized and stored in the cytoplasm for use over long periods. This pattern of regulation was found for three individual proteins isolated from the oral apparatus fraction after extraction with a phenol-acetic acid solvent. A different pattern of regulation was found for microtubule proteins isolated from the oral apparatus of Tetrahymena. The data suggest that microtubule proteins, at least in logarithmically growing cells, are not stored in a cytoplasmic pool but are synthesized in the same cell cycle in which they are assembled into oral structures.

Animals↗
PubMed1971

Streptomycin uptake by Mycobacterium tuberculosis.

Data are presented indicating that (14)C-streptomycin uptake by tubercle bacilli increases as a function of exposure time, is directly and proportionately related to concentration, and involves at least two phases.

Carbon Isotopes↗