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Biomedical subjects

G A Thompson

Publications and source records attributed to G A Thompson.

At least 145 records · Page 8Linked to original sources
PubMed1984

The influence of diazepam on the serum protein binding of bupivacaine at normal and acidic pH.

Since both bupivacaine and diazepam are highly protein bound, it is possible that a drug displacement interaction could occur, resulting in an increase in free bupivacaine concentration that could exacerbate systemic toxicity. This study was undertaken to characterize the serum binding of diazepam and to evaluate any drug displacement interaction between diazepam and bupivacaine. Human serum obtained from venous blood of normal male and female volunteers was used for measurements of protein binding using an Amicon Micropartition System. Bupivacaine protein binding in the presence of 0, 0.5 and 1.5 microgram/ml diazepam was best described by the model for two classes of binding sites. Neither concentration of diazepam significantly altered the capacity or affinity for either class of bupivacaine binding sites when compared to control. Free concentrations of bupivacaine were statistically identical in the presence of both diazepam concentrations. The complete diazepam binding profile in both serum and isolated human serum albumin was best described by a model describing two classes of binding sites. The effect of an acidic pH on bupivacaine was also independent of diazepam concentration. Diazepam protein binding was not affected by a reduction in pH from 7.4 to 7.0. The data reported here suggest no binding displacement interaction exists between bupivacaine and concomitantly administered diazepam. Thus, administration of diazepam during a toxic reaction associated with bupivacaine should not alter free bupivacaine concentration.

Acidosis↗
PubMed1984

Continuous perineural infusions of bupivacaine for prolonged analgesia--a rapid two-point method for estimating individual pharmacokinetic parameters.

Results of previous studies have shown a 5-10 fold range in the clearance total and half-life of bupivacaine. Since bupivacaine has a narrow therapeutic range and highly variable pharmacokinetic parameters, rapid estimation of the parameters allows early dosage regimen adjustments, and hence, better pain management. The pharmacokinetic parameters in 17 patients were estimated based on two samples drawn within 18 h after initiation of therapy. Based on the estimated parameters, a later sample's concentration was predicted. Results of this study confirm the previously reported large variation in pharmacokinetic parameters. An excellent agreement between actual and predicted concentration was found. The use of this method allows early readjustment in the dosage regimen, resulting in effective pain management without compromising patient safety.

Aged↗
PubMed1984

Pharmacokinetics and neural blockade after subarachnoid lidocaine in the rhesus monkey. III. Effects of phenylephrine.

Using a rhesus monkey model, lidocaine (30 mg) in 7.5% dextrose was compared with lidocaine (30 mg) in 7.5% dextrose containing 1.5 mg of phenylephrine (Neosynephrine). Phenylephrine increased both duration of maximum motor block and time for complete motor recovery. A significantly higher sensory dermatome level and significantly longer time for complete sensory recovery was found when the lidocaine solution contained phenylephrine. Time for two-segment regression of sensory blockade was unaffected by phenylephrine. The slope of the regression phase for motor block was parallel for both treatments, suggesting differences in neural blockade were caused by a more profound initial block when phenylephrine was added. Pharmacokinetic analysis revealed identical absorption and elimination constants. Maximum plasma concentrations of lidocaine and time to reach maximum plasma concentrations were identical with and without phenylephrine. The systemic absorption (fraction of drug absorbed from the subarachnoid space) was complete with and without phenylephrine. No lag times for systemic absorption were found for either treatment. Our data demonstrate that there are no clinically significant differences between phenylephrine and epinephrine when added to lidocaine solutions for spinal anesthesia.

Anesthesia, Spinal↗
PubMed1983

Cold stress induces in situ phospholipid molecular species changes in cell surface membranes.

The structural organization of Tetrahymena pyriformis is such that its cilia are remote from the main centers of lipid metabolism. As a result, the ciliary membrane lipid composition of cells exposed to low-temperature stress is initially unaffected by the significant metabolic changes induced in microsomal membranes. Nevertheless, changes in the ciliary membrane lipid composition can be detected during the first 4 h of cold exposure. A combination of in vivo and in vitro experiments has provided strong evidence for a substantial retailoring of ciliary phospholipid molecular species in situ in the absence of any importation of lipids from the cell interior or change in overall ciliary fatty acid composition. The mechanism responsible for the ciliary lipid changes is independent of the one(s) triggering internal acclimation responses. Our observations establish for the first time that chilling stress can simultaneously induce separate and distinctive lipid modification responses in different parts of a cell. This finding could be important in identifying the molecular 'sensor' capable of actuating stress-induced lipid changes.

Acclimatization↗
PubMed1983

Adaptation of Lemna paucicostata to Sublethal Methionine Deprivation.

During initial exposure to 40 nanomolar propargylglycine (PAG), Lemna paucicostata colonies undergo abnormal fragmentation and a lag in frond emergence, most severe at 24 to 48 hours. Thereafter, frond emergence resumes and the frond/colony ratio rises. Such ;adapted' plants withstand subculture into the same concentration of PAG without fragmentation or decreases in frond emergence, and display enhanced tolerance to higher concentrations. Adaptation is not dependent upon outgrowth of a few preexisting especially tolerant plants. Exogenous methionine prevents these events and overcomes the PAG-induced lag in frond emergence even after it is underway. These changes in frond emergence are not reflected in the rates of protein and wet weight accumulation which decrease by about 25% during the first 24 hours and continue unchanged thereafter. Cystathionine gamma-synthase activity rapidly decreases to 9% of control during the first 12 hours of exposure to 40 nanomolar PAG but thereafter climbs to 12% of control. Studies of the uptake and internal concentration of PAG during these events are reported.Exposure to a combination of 36 micromolar lysine plus 3 micromolar threonine is an alternative means to bring about sublethal methionine deprivation. Thus exposed, Lemna undergoes an analogous sequence of effects on morphology and growth which are preventable by exogenous methionine and which lead to an adapted state. Cystathionine gamma-synthase specific activity in plants adapted to 36 micromolar lysine plus 3 micromolar threonine is 1.8 times control. However, addition of PAG showed that under these conditions enzyme activity can be decreased to as little as 54% of control without affecting the growth rate. Together these results suggest that adaptation is related to methionine limitation and that the plants adjust, in part, by increasing the steady-state concentrations of cystathionine gamma-synthase and other enzymes in the methionine pathway.

Journal Article↗
PubMed1983

In vivo metabolism of 5'-methylthioadenosine in lemna.

Evidence is presented that Lemna converts 5'-methylthioadenosine (MTA) to methionine. The methylthio moiety and four of the ribose carbons of the nucleoside contribute the methylthio and the four-carbon moieties of methionine. Plants grown in the presence of inhibitors which block methionine biosynthesis convert MTA to methionine at a rate sufficient to sustain normal growth (at least 4.4 nanomoles per colony per doubling with a molar yield of at least 65%). The pathway for conversion is shown to be constitutive in plants grown in standard medium and to function at a rate sufficient to dispose of MTA arising as a result of polyamine synthesis, and to explain the observed rate (1.4 nanomoles per colony per doubling) of preferential recycling of methionine sulfur (Giovanelli, Mudd, Datko 1981 Biochem Biophys Res Commun 100: 831-839). Rapid entry of methionine methyl into S-adenosylmethionine and phosphorylcholine was observed for plants grown in standard medium. Adenine generated during this cycle is efficiently salvaged into ADP and ATP.Conversion of MTA to methionine completes the steps in methionine thiomethyl recycling (Giovanelli, Mudd, Datko 1981 Biochem Biophys Res Commun 100: 831-839) in which the sulfur of methionine is retained while the four-carbon moiety is not. The findings further show that the four-carbon moiety of methionine can be derived via the ribose moiety of MTA in addition to the established route from O-phosphohomoserine via transsulfuration. Previous observations (Giovanelli, Mudd, Datko 1980 Biochemistry of Plants pp 453-505) can now be interpreted as establishing that exogenous methionine down-regulates its own net synthesis via the transsulfuration pathway.

Journal Article↗
PubMed1983

Separation of galactolipid molecular species by high-performance liquid chromatography.

A technique for the separation, detection, and quantification of molecular species of monogalactosyldiglyceride and digalactosyldiglyceride is described. Use of the technique to analyze the molecular species composition of the galactolipids isolated from Dunaliella salina chloroplasts is presented. The results indicate that the respective compositions of the two lipids are quite different. This suggests that the enzymes involved in galactolipid metabolism are very specific with respect to acyl chain composition and pairing, or that extensive retailoring of constituent acyl chains occurs following formation of digalactosyldiglyceride from monogalactosyldiglyceride.

Journal Article↗
PubMed1982

Gorlin's syndrome, or nevoid basal cell carcinoma syndrome.

Gorlin's syndrome is a condition inherited in an autosomal dominant fashion. It involves many organs, but principally affects the skin, skeleton, and endocrine and nervous systems. The most common features are multiple nervi and basal cell carcinomas of the skin, benign jaw cysts, dyskeratotic pits in the palms and soles, rib and vertebral abnormalities, brachymetacarpalism, and calcification of the falx cerebri. In 14 patients, 4 of whom belonged to one family, the age at the time of diagnosis ranged from 11 to 63 years. Ten patients are alive, but five are severely disfigured by carcinomas. Two patients died of complications resulting from uncontrolled tumours, and two died of other cancers. New skin tumours constantly develop; small ones can be excised, but large ones require extensive surgery with or without radiotherapy.

Adolescent↗
PubMed1982

Phospholipid molecular species alterations in Tetrahymena ciliary membranes following low-temperature acclimation.

The molecular species compositions of phosphatidylcholine, phosphatidylethanolamine, and 2-(aminoethyl)-phosphonolipid, the three principal phosphoglycerides of Tetrahymena pyriformis ciliary membranes, have been determined by coupled gas chromatography-mass spectrometry of the tert-butyldimethylsilyl derivatives of their phospholipase C derived diglycerides. There were striking changes in the molecular species composition of phosphatidylcholine and phosphatidylethanolamine after the cells were chilled from 39 to 15 degrees C. The low temperature induced changes occurring in each phospholipid class were markedly different from those taking place in the other two. The molecular species patterns of the ciliary phosphoglycerides resembled in a qualitative way the patterns found in their microsomal counterparts. However, the relative proportions of many molecular species within each ciliary phospholipid class were very different from those of the corresponding microsomal component, and changes induced in a particular microsomal phospholipid class by chilling were often absent or even reversed in the equivalent ciliary phospholipid. Compositional changes in ciliary phospholipids during low-temperature acclimation were greater in nearly all respects than were concurrent changes in microsomal phospholipids. The molecular species data confirm that the cell possesses a variety of highly selective mechanisms allowing those organelles which accept phospholipids of microsomal origin to retain a surprising degree of independence in responding to environmental stress.

Acclimatization↗
PubMed1982

Methionine Biosynthesis in Lemna: STUDIES ON THE REGULATION OF CYSTATHIONINE gamma-SYNTHASE, O-PHOSPHOHOMOSERINE SULFHYDRYLASE, AND O-ACETYLSERINE SULFHYDRYLASE.

Regulation of enzymes of methionine biosynthesis was investigated by measuring the specific activities of O-phosphohomoserine-dependent cystathionine gamma-synthase, O-phosphohomoserine sulfhydrylase, and O-acetylserine sulfhydrylase in Lemna paucicostata Hegelm. 6746 grown under various conditions. For cystathionine gamma-synthase, it was observed that (a) adding external methionine (2 mum) decreased specific activity to 15% of control, (b) blocking methionine synthesis with 0.05 muml-aminoethoxyvinylglycine or with 36 mum lysine plus 4 mum threonine (Datko, Mudd 1981 Plant Physiol 69: 1070-1076) caused a 2- to 3-fold increase in specific activity, and (c) blocking methionine synthesis and adding external methionine led to the decreased specific activity characteristic of methionine addition alone. Activity in extracts from control cultures was unaffected by addition of methionine, lysine, threonine, lysine plus threonine, S-adenosylmethionine, or S-methylmethionine sulfonium to the assay mixture. Parallel studies of O-phosphohomoserine sulfhydrylase and O-acetylserine sulfhydrylase showed that O-phosphohomoserine sulfhydrylase activity responded to growth conditions identically to cystathionine gamma-synthase activity, whereas O-acetylserine sulfhydrylase activity remained unaffected. Lemna extracts did not catalyze lanthionine formation from O-acetylserine and cysteine. Estimates of kinetic constants for the three enzyme activities indicate that O-acetylserine sulfhydrylase has much higher activity and affinity for sulfide than O-phosphohomoserine sulfhydrylase.The results suggest that (a) methionine, or one of its products, regulates the amount of active cystathionine gamma-synthase in Lemna, (b) O-phosphohomoserine sulfhydrylase and cystathionine gamma-synthase are probably activities of one enzyme that has low specificity for its sulfur-containing substrate, and (c) O-acetylserine sulfhydrylase is a separate enzyme. The relatively high activity and affinity for sulfide of O-acetylserine sulfhydrylase provides an explanation in molecular terms for transsulfuration, and not direct sulfhydration, being the dominant pathway for homocysteine biosynthesis.

Journal Article↗
PubMed1982

Low Temperature-Induced Alterations in the Chloroplast and Microsomal Membranes of Dunaliella salina.

The metabolic regulation of membrane lipid composition has been examined using the cell wall-less, unicellular green alga Dunaliella salina (UTEX 1644) as a model system. Low temperature stress was employed to initiate and study the regulatory response.When cultures growing logarithmically at 30 degrees C were chilled to 12 degrees C, cell division ceased for approximately 100 hours, and then the cells resumed logarithmic growth at a slower rate. The phospholipid, glycolipid and protein content, on a per cell basis, was, in each case, approximately 20% higher in cells grown at 12 degrees C. The volume of the 12 degrees C-acclimated cells was 2.8 times that of 30 degrees C-grown cells. The quantity of chloroplast membrane, as determined by morphometric analysis, was 20% greater, whereas the content of microsomal membrane material was more elevated, being approximately 2.8 times that of 30 degrees C-grown cells.Lipid compositional analyses were carried out on purified chloroplasts and microsomes isolated from Dunaliella grown at 30 and 12 degrees C and also from cells 12 and 60 hours following a shift from 30 to 12 degrees C. In both chloroplast and microsomal phospholipids fatty acid unsaturation increased during acclimation to low temperature. Generally, microsomal phospholipids responded more quickly and to a greater extent than did chloroplast phospholipids. Despite these alterations, little change in the relative proportions of phospholipid classes was observed in either cell fraction.In sharp contrast to the pattern of phospholipid change, chloroplast glycolipids responded to low temperature by significantly increasing the proportion of one specific class, digalactosyl diglycerides, relative to monogalactosyl diglycerides, while showing minimal change in fatty acid distribution within any given glycolipid class.The ease and rapidity with which Dunaliella cells can be manipulated with respect to environmental stress and isolation of intact cell organelles makes it particularly well suited for research on intermembrane lipid dynamics within the plant cell.

Journal Article↗
PubMed1982

Methionine Synthesis in Lemna: Inhibition of Cystathionine gamma-Synthase by Propargylglycine.

Propargylglycine, vinylglycine, and cysteine each cause irreversible inactivations of cystathionine gamma-synthase (and, in parallel, of O-phosphohomoserine sulfhydrylase) activities in crude extracts of Lemna paucicostata. Inactivation by propargylglycine or vinylglycine is completely prevented by 40 millimolar O-phospho- or O-succinyl-l-homoserine; that by cysteine is only partially prevented. Propargylglycine (PAG), the most potent of these inhibitors, causes rapid and drastic inactivation of both activities in intact Lemna. Studies of plants growing in steady states in the presence of various concentrations (0-150 nanomolar) of PAG showed that 16% of control activity is necessary and sufficient to maintain normal rates of growth and methionine biosynthesis, and that 10% of control activity is essential for viability. Addition of either 2 micromolar methionine or 31 micromolar cystine to growth medium containing 150 nanomolar PAG permits growth at 75 to 100% of control rates when enzyme activity is less than 10% of control. Whereas methionine presumably rescues by directly providing the missing metabolite, cystine may rescue by enhancing substrate accumulation and thereby promoting flux through residual cystathionine gamma-synthase. The results indicate that the down-regulation of cystathionine gamma-synthase to 15% of control which occurs when plants are grown in 2 micromolar methionine (Thompson, Datko, Mudd, Giovanelli Plant Physiol 69: 1077-1083), by itself, is not sufficient to reduce the rate of methionine biosynthesis.

Journal Article↗