Biomedical subjects
Publications and source records attributed to N E Williams.
The effect of urine pH on the plasma concentration and elimination of phenoperidine and its main metabolites was studied in six volunteers. The clearance of unchanged phenoperidine in acid urine was significantly greater than in neutral or alkaline urine. By contrast, the elimination of its basic metabolites was enhanced in uncontrolled or alkaline urine. Other pharmacokinetic parameters were not significantly affected.
The induced synthesis of identified surface membrane proteins has been demonstrated in deciliated Tetrahymena. Cells in the process of regenerating cilia were also studied using transmission electron microscopy in order to obtain information on the deployment of new membrane at the cell surface. The results obtained suggest a pattern of membrane flow that includes the 'pellicular alveoli', a subsurface membrane system characteristically present in ciliated protozoa. The results of 125I surface-marking experiments were consistent with the notion that new membrane is added initially in non-ciliated regions, then subsequently flows laterally to cover regenerating cilia.
The effects of atracurium besylate 0.3 mg kg-1 or 0.6 mg kg-1 on neuromuscular function were assessed by electromyography in 11 normal subjects, using successive trains of four supramaximal stimuli. After the induction of anaesthesia, the relation between the reduction in the amplitude of the compound muscle action potential and decrement was studied during the onset and recovery of nondepolarizing blockade. During induction, the decrease in the amplitude of the initial compound muscle action potential was usually greater than decrement, and resembled the pattern observed with pancuronium. In contrast, during recovery from myoneural blockade, decrement was invariably greater than the reduction in the amplitude of the action potential. It was considered that these effects were consistent with the action of atracurium on more than one group of receptors at the neuromuscular junction. The effects of atracurium were rapidly antagonized by neostigmine, and supplementary doses of the drug showed no evidence of cumulation.
Proteins of surface membranes and surface-related cytoskeletons in Tetrahymena vorax microstomes and macrostomes were compared by one-dimensional SDS polyacrylamide gel electrophoresis to see if protein differences could be detected that correlate with the transformation from one phenotype to the other. Some differences were observed. However, these alterations appear to result from the heat-shock procedure used to synchronize the microstome-to-macrostome transition. The apparent lack of transformation-specific changes in cortical proteins is discussed. Similarities and differences between cytoskeletal proteins of T. pyriformis GL-C and T. vorax are also noted and discussed.
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Case histories of three patients with intractable pain, all of whom responded to epidural morphine, are presented. Drug tolerance appeared to develop in two patients who survived longer than 10 days. Nevertheless this method of pain relief may be a useful adjunct to terminal care and in certain circumstances may allow for easier management in the patient's own home.
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Tetrahymena thermophila strain B could regenerate approximately 10% of its somatic ciliary mass in concentrations of cycloheximide believed to block all cytoplasmic protein synthesis. A quantitative study of the relative numbers and lengths of cilia regenerated in the presence and absence of cycloheximide under a variety of conditions suggested that specific initiation and elongation protein factors are involved in the control of ciliary morphogenesis in Tetrahymena.
The synthesis of ciliary-membrane phospholipids and ciliary proteins was studied after deciliation in starving Tetrahymena thermophila cells. Deciliated cells regenerated the new ciliary membrane without any induced phospholipid synthesis. The constant cell volume found during the regrowth of the cilia suggests that renewal of ciliary membranes takes place by insertion of intracellular membrane material into the cell surface. In contrast with the absence of induced phospholipid synthesis during ciliary regeneration, the synthesis of ciliary proteins was found to be induced. This enhanced synthetic activity was made possible by an increased rate of intracellular protein degradation in regenerating cells. It was found that the extent of the induced synthesis strongly depends upon the growth conditions of the cells before starvation. Furthermore, it was shown that the degree of induced protein synthesis is greater for higher-molecular-weight ciliary proteins than for lower-molecular-weight species.
Membrane proteins within cell fractions of Tetrahymena have been separated by polyacrylamide gel electrophoresis and the turnover of these proteins has been studied in nongrowing cells using double labeling procedures. Lactoperoxidase iodination and two-dimensional gel separations have revealed over 20 surface-labeled proteins, two of which are responsible for the single peak found in ciliary and nonciliary surface membranes. Turnover measurements show that there is heterogeneity in the rates at which membrane proteins turn over. The data suggest that larger proteins may turn over at higher rates in the microsomal fraction, as previously shown in mammalian cells. This was not found in the surface membrane fractions of Tetrahymena. However, membrane-associated cytoskeletal proteins had lower turnover rates than integral membrane proteins, and significant heterogeneity was found among the integral proteins measured. The implications of these findings for possible modes of membrane biogenesis in Tetrahymena are discussed.
The relationship between the depression in the amplitude of the compound muscle action potential and neuromuscular decrement (fade) was studied during the induction of non-depolarizing blockade, using a train of four supramaximal stimuli. Neuromuscular decrement (%) was defined as: [1 - (amplitude of fourth muscle action potential)/(amplitude of first muscle action potential)] x 100. When the amplitude of the first action potential was reduced by 50%, mean neuromuscular decrement increased in the order pancuronium < alcuronium < tubocurarine < frazadinium < gallamine. Similarly, the slope of the regression line relating the decrease in the amplitude of the action potential to decrement was least with pancuronium and greatest with gallamine. These results may reflect different affinities or intrinsic activities of the five drugs for prejunctional and postjunctional receptors. Thus, pancuronium may have a greater affinity for postsynaptic receptors, while tubocurarine and gallamine affect selectively the motor nerve terminal. It was confirmed that fazadinium had a more rapid onset on action than any of the other myoneural blocking drugs studied.
The plasma concentrations of phenoperidine were measured in five patients during general anaesthesia. The concentration of the drug decreased rapidly between 2 and 40 min and then declined more slowly. Detectable concentrations of phenoperidine were present in plasma for at least 3 h. In the five patients, the distribution half-life of the drug ranged from 3.19 to 14.23 min and the elimination half-life from 47.31 to 162.30 min. Unchanged phenoperidine and two identified metabolites (pethidine and norpethidine) were present in urine.
Simple media for Tetrahymena, using rat gut or soybean as the nutrient source are described. Cultures can be maintained in these media up to one year at room temperature.
Surface proteins of Tetrahymena were identified by lactoperoxidase iodination, and comparisons were made between a number of strains and species within the genus. An adequate procedure for strain comparisons was found to be solubilization of whole cells following iodination, separation of total cell protein using polyacrylamide gel electrophoresis, and identification of surface proteins by autoradiography of dried gels. The results obtained in the present study show the existence of both interspecific and intraspecific variation in surface proteins of tetrahymena, but the differences tend to be small within species and large between species. The relation of these cell surface fingerprints to the present taxonomic designations within the genus is discussed. Questions are raised about the functional significance of these surface proteins.
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Eleven patients were investigated for pituitary function after the injection of alcohol into the pituitary fossa; all had persistent pain and 8 had carcinoma of the breast. Most of the patients showed varying degrees of reduction of pituitary activity; 8 patients obtained significant pain relief and 3 patients exhibited polyuria. These 3 observations could not be completely correlated; the possible mechanisms which may lead to pain suppression by this method are discussed.
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