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Biomedical subjects

G A Thompson

Publications and source records attributed to G A Thompson.

At least 181 records · Page 10Linked to original sources

Membrane changes during growth of Tetrahymena in the presence of ethanol.

After a brief lag period for acclimation, Tetrahymena pyriformis, strain NT-1, is capable of growing in culture medium containing high levels of ethanol. When grown in a medium having 1.6% ethanol, the membrane phospholipid composition was significantly different from that of control cells. The principal changes included a reduction in hexadecenoic acids (16 : 1 and 16 : 2) from 23% to 5% and an increase in linoleic acid (18 : 2) from 14% to 25% Similar but less pronounced changes were observed in cells grown in lower ethanol concentrations. There was also a decrease in 2-aminoethylphosphonolipid in the ethanol-grown cells from 16% of the lipid phosphorus to 6% and a coincident rise in the phosphatidylethanolamine from 39% to 46%. The lipid pattern quickly reverted to normal when ethanol was removed. In order to ascertain the effects of ethanol on membrane physical properties, freeze-fracture electron microsocopy and fluorescence polarization studies were performed. Ethanol, as expected, had a clearly detectable fluidizing influence when present at 1.6%. However, changes induced in the membrane lipids by growth in the ethanol-containing medium led to a further fluidizing effect, whether they were tested in the presence or absence of ethanol. The alterations found here were qualitatively similar but quantitatively much more pronounced than those observed in mammals chronically exposed to ethanol.

Cell Membrane↗

Temperature-induced changes in fatty acid unsaturation of Tetrahymena membranes do not require induced fatty acid desaturase synthesis.

The usual rise in phospholipid-bound palmitoleic acid of Tetrahymena pyriformis cells slowly acclimating to low temperature exposure can be prevented by cycloheximide. This reduction in fatty acid desaturation is not caused by specific inhibition of a temperature-induced synthesis of a fatty acid desaturase but rather by a general effect equally conspicuous in isothermal cells. Cycloheximide-inhibited cells chilled and analyzed quickly, before long term ill effects of the drug are expressed, exhibit the rise in unsaturated fatty acids typical of temperature-acclimating cells.

Animals↗

The one-point method in predicting dosage regimen in case of hepatic and/or renal failure in presence or absence of change in volume of distribution.

In some clinical situations such as in acute myocardial or coronary infarction, liver disease, renal failure, hypoalbuminemia, displacement from protein binding, etc., both the volume of distribution and the elimination rate may change. The determination of the creatinine clearance may be too time consuming, and the serum creatinine concentration may be an unreliable indicator in some cases (acute renal failure, uremia, muscular diseases, old age, etc). Neither indicates change in elimination by extrarenal routes (metabolism in liver disease). The "repeated one-point method" is presented as clinical tool to calculate the dosage regimen for patients where differences in Vd and kel can be expected. The method is based on the evaluation of one blood sample each in the first two dosing intervals after administration of a test dose. The "repeated one-point method" is compared with the previously published "one-point method."

Creatinine↗

Increased levels of adenosine 3',5'-cyclic monophosphate in Tetrahymena stimulated by glucose and mediated by Ca2+ and epinephrine.

Stationary phase Tetrahymena cells exposed to 0.5-1% glucose experience an 8-fold increase in intracellular cyclic AMP within 1 hr. The increase follows an enhanced uptake of Ca2+ triggered by the glucose addition. Inhibiting the Ca2+ influx with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid blocks the increase in cyclic AMP, but the block can be reversed by the addition of epinephrine. Both this epinephrine effect and the glucose-induced increase in cyclic AMP are counteracted by the beta-adrenergic inhibitor dichloroisoproterenol.

Animals↗

Operant control of pathological tongue thrust in spastic cerebral palsy.

Pathological tongue thrust (reverse swallowing) has been associated with neuromuscular disorders and linked to dental malocclusion, articulation problems, difficulty in eating, and excessive drooling. In this study, observable tongue thrust in a 10-year-old retarded male was modified during mealtime using a procedure consisting of differential reinforcement (presentation of food contingent upon tongue in) and punishment (gently pushing the tongue back into the mouth with a spoon). Results of a reversal design showed substantial decreases in tongue thrust and food expulsion, and a large increase in observed chewing. These data compared favorably with data obtained for other retarded persons not judged to be tongue thrusters; in addition, the objective results of the treatment program were substantiated via pre-post evaluations done by occupational and physical therapists. These findings suggest that operant techniques may be an effective means of treating tongue thrust and its associated problems, and that further development and evaluation of behavioral interventions may provide a desirable alternative to more intrusive surgical or mechanical procedures.

Aversive Therapy↗

An analysis of corneal transplantation: I--graft clarity.

A retrospective review has been undertaken of the clarity results of 378 keratoplasties performed by 6 Toronto corneal surgeons between January 1970 and December 1974. Lamellar keratoplasties were included in the data related to herpes simplex only. In herpes simplex penetrating grafts gave better vision than lamellar grafts. The following factors were statistically important with respect to graft clarity: age of recipient, type of corneal disease, peroperative corneal vessels, first or subsequent graft, pre- and/or postoperative glaucoma, postoperative anterior synechiae, combined procedure, vitreous loss, previous cataract surgery, and follow-up time. The following factors were statistically unimportant with respect to graft clarity: donor age, time from death to enucleation (median 2.8 hours), time from enucleation to use (median 24 hours), sex of donor and recipient, interrupted or running suture, use of microscope, penetrating or lamellar graft in herpes simplex, postoperative astigmatism, and division of postoperative anterior synechiae. Silk (compared with nylon), larger grafts and combined procedures all increased the incidence of graft rejection. Repeat grafts were associated with more preoperative corneal vascularization.

Adolescent↗

An analysis of corneal transplantation: II--postoperative astigmatism.

An analysis of 153 penetrating keratoplasties was undertaken. The same surgical technique was used in all cases. Three factors had a statistically significant effect on postoperative astigmatism, as measured by keratometry. (1) Astigmatism decreased with increasing follow-up time (P less than 0.05). (2) Vitreous loss at the time of the keratoplasty increased the amount of postoperative astigmatism (P less than 0.05). (3) Females had more postoperative astigmatism than males (P less than 0.05), but this was probably related to a tendency for females to have a greater incidence of postoperative anterior synechiae (P just greater than 0.05), and the fact that all 6 cases of vitreous loss were in females. There was an almost significant trend toward postoperative anterior synechiae being associated with increased astigmatism (P just greater than 0.05), and there was also a trend toward the division of these synechiae reducing the amount of astigmatism. Fifteen of the 153 penetrating grafts were done in cases of herpes simplex. These were compared with 11 lamellar grafts done for herpes simplex, and there was a statistically insignificant trend toward more postoperative astigmatism in penetrating grafts.

Astigmatism↗

Use of fluorescence polarization to monitor intracellular membrane changes during temperature acclimation. Correlation with lipid compositional and ultrastructural changes.

Fluorescence polarization of 1,6-diphenylhexatriene (DPH) was used to study the effects of temperature acclimation on Tetrahymena membranes. The physical properties of membrane lipids were found to be highly dependent on cellular growth temperature. DPH polarization in lipids from three different membrane fractions correlated well with earlier freeze-fracture and electron spin resonance observations showing that membrane fluidity progressively decreases in the order microsomes greater than pellicles greater than cilia throughout a wide range of growth temperatures. Changes in membrane lipid fluidity following a shift from high to low growth temperatures proceed rapidly in the microsomes, whereas there is a pronounced lag in the changes of peripheral cell membrane lipids. These data support previous observations that adaptive changes in membrane fluidity proceed via lipid modifications in the endoplasmic reticulum, followed by dissemination of lipid components to other cell membranes. The rapid changes in polarization observed in the microsomal lipids following a temperature shift correspond closely with the time-dependent alterations in both lipid fatty acid composition and freeze-fracture patterns of membrane particle distribution, suggesting that, in the endoplasmic reticulum, lipid phase separation is the primary cause of membrane particle rearrangements.

Animals↗

The predictive value of leucocyte migration inhibition test in human keratoplasty.

We compared the results of penetrating keratoplasty in 18 patients whose preoperative or immediate postoperative leucocyte migration inhibition (LMI) tests were positive (greater than 20% inhibition) with those in 15 patients whose LMI tests were negative. A negative LMI test indicated a greater chance of avoiding graft rejection (P less than 0.005), and of ending up with a clear graft (P less than 0.05).

Cell Migration Inhibition↗

Pharmacokinetics of antimalarials and proposals for dosage regimens.

Blood level data for the antimalarials amodiaquine, chloroguanide, chloroquine, pyrimethamine, quinine and sulphadoxine have been retrieved from the literature and pharmacokinetically analyzed. Minimum, average and maximum blood level concentrations at steady state in suppressive treatment and peak concentrations in therapeutic treatment were predicted and blood level-time curves simulated. Based on the computer-predicted data, changes in dosage regimens are proposed to reduce the fluctuations between maximum and minimum levels in suppressive treatment, and for obtaining maximum peak levels in therapeutic treatment already with the loading dose.

Antimalarials↗

Self-regulation of membrane fluidity. The effect of saturated normal and methoxy fatty acid supplementation on Tetrahymena membrane physical properties and lipid composition.

Tetrahymena cells elongated and desaturated massive supplements of palmitic or lauric acid at nearly twice the rates employed by unfed cells, thereby maintaining constant the physical properties of their membrane lipids. However, when a mixture of the 9- and 10-monomethoxy derivatives of stearic acid was administered, these compounds were incorporated without further metabolism. The marked fluidizing effect of the phospholipid-bound methoxy-fatty acids elicited an immediate reduction in fatty acid desaturase activity, the pattern of change being very similar to that induced by supplements of polyunsaturated fatty acids. The modulation of fatty acid desaturase activity by methoxy-acids clearly seems to be governed by membrane fluidity rather than by some form of end product inhibition of the type which might have been postulated to explain the similar effect caused by polyunsaturated fatty acids.

Animals↗

Tetrahymena strives to maintain the fluidity interrelationships of all its membranes constant. Electron microscope evidence.

When cells of Tetrahymena pyriformis, strain NT-1, were chilled from their growth temperature of 39.5 degrees C to lower temperatures, the plasma membrane, outer alveolar, nuclear, outer mitochondrial, food vacuolar, and endoplasmic reticulum membranes each responded in a fashion quite characteristic of the membrane type. In most cases a distinctive rearrangement of intramembrane particles, as discerned by freeze-fracture electron microscopy, began abruptly at a definitive temperature. By comparing the freeze-fracture patterns of membranes in cells grown at 39.5, 27, and 15 degrees C, it was shown that the initial particle rearrangement in a given membrane always occurred at a fixed number of degrees below the growth temperature of the cell. Gradual chilling of a cell grown at constant temperature induced these membrane changes first in the outer alveolar membrane, then, in order of decreasing response to temperature, in the endoplasmic reticulum, outer mitochondrial membrane, nuclear envelope, and vacuolar membrane. The normally stable relationships between the physical properties of the several membrane types could in some cases be reversed, but only temporarily, by fatty acid supplementation or during the initial phases of acclimation to growth at a different temperature. The system provides a unique opportunity to study the effects of environmental change upon the physical properties of several functionally distinct but metabolically interrelated membranes within a single cell.

Animals↗

Differentiation of food vacuolar membranes during endocytosis in Tetrahymena.

The origin and differentiation of Tetrahymena pyriformis food vacuolar membranes has been studied by freeze-fracture electron microscopy. By measuring the temperature needed to induce the onset of lipid phase separation (as inferred by the appearance of particle-free regions in replicas) and calculating the changes in average intramembrane particle distribution, a distinct modification of the vacuolar membrane could be observed from the time of its formation from disk-shaped vesicles to its maturation before egestion of its indigestible contents. Whereas the nascent vacuolar membrane first showed signs of phase separation at 9 degrees C, this temperature rose to 14 degrees C in the completed vacuole and then, after lysosomal fusion, eventually declined to 12 degrees C. The average membrane particle density on the PF face increased from 761 +/- 219 to 1,625 +/- 350 per micron 2 during membrane differentiation. Like other membranes of the cell, the vacuolar membrane underwent adaptive changes in its physical properties in cells maintained for several hours at low temperature. This exposure to low temperature caused an equal effect in vacuoles formed before, during, or after the temperature shift-down. Normal changes in the properties of the vacuolar membrane may have some bearing on its programmed sequence of fusion reactions.

Animals↗

Molecular control of membrane properties during temperature acclimation. Fatty acid desaturase regulation of membrane fluidity in acclimating Tetrahymena cells.

This is a study of the molecular mechanisms employed by Tetrahymena pyriformis to change the lipid composition and thereby the fluidity of its various membranes during temperature acclimation. By quantitatively measuring the intramembrane particle aggregation using freeze-fracture electron microscopy, membrane physical properties in 39.5 degrees C grown cells shifted to 15 degrees C were found to be correlated with the degree of phospholipid fatty acid desaturation. Alteration of the phospholipid polar head group distribution from that of 39.5 degrees C-grown cells to the significantly different pattern of 15 degrees C grown cells appeared not to be of critical importance in the acclimation process. Changes in fatty acid desaturation during acclimation from high to low temperatures and vice versa were analyzed using normal cells and cells fed large amounts of polyunsaturated fatty acids. Fatty acid desaturase activity corresponded to the degree of membrane fluidity but not to the cell temperature. All evidence was compatible with the hypothesis that membrane fluidity is self-regulating, with the action of fatty acid desaturases being modulated by the physical state of their membrane environment.

Acetates↗