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S L Smith

Publications and source records attributed to S L Smith.

At least 19 recordsLinked to original sources
PubMed1992

Substoichiometric inhibition of microtubule formation by acetaldehyde-tubulin adducts.

We have shown previously that acetaldehyde forms stable covalent adducts with tubulin, resulting in impaired microtubule formation. The present study explored the mechanism responsible for impaired microtubule formation caused by the substoichiometric stable binding of acetaldehyde to tubulin. The free tubulin dimer was much more reactive with acetaldehyde than microtubules, binding more than twice as much aldehyde. The dimer also formed nearly twice as many stable adducts on its alpha-chain as on its beta-chain, whereas microtubules exhibited an equal distribution of adducts between the two subunits. These data confirm that the alpha-chain of free tubulin, but not microtubules, has an accessible highly reactive lysine (HRL) residue that is a preferential target of acetaldehyde binding. Adduct formation with the HRL residue also correlated with impaired tubulin polymerization, and only 0.08 moles of acetaldehyde bound per mole of HRL was required for complete inhibition; however, adducts with other lysine residues (bulk adducts) did not affect assembly. Adducts to microtubule-associated proteins (MAPs) also impaired the assembly of tubulin, but were much less effective than HRL adducts. In a copolymerization assay, HRL-adducted tubulin, in addition to being itself assembly incompetent, also interfered with polymerization of normal (unadducted) tubulin. Bulk adducts did not alter assembly and were incorporated normally into the growing polymer. When tubulin was cleaved by the proteolytic enzyme, subtilisin, microtubule formation could readily take place in the absence of MAPs. In this polymerization system, HRL adducts, but not bulk adducts, still markedly inhibited assembly. When low concentrations of acetaldehyde (50 microM) were used to generate HRL adducts, an adduct on only 1 out of 20 tubulin molecules was sufficient to totally block polymerization. These findings indicate that substoichiometric amounts of acetaldehyde bound to HRL of tubulin can markedly inhibit microtubule formation via direct interference of dimer-dimer interactions, and further suggest that low concentrations of acetaldehyde could generate sufficient amounts of HRL adducts in cellular systems to alter microtubule formation and function.

Acetaldehyde↗
PubMed1992

Effects of the adenylate cyclase activator forskolin and its inactive derivative 1,9-dideoxyforskolin on insect cytochrome P-450 dependent steroid hydroxylase activity.

The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae of Drosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm, Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5 x 10(-6) to 5 x 10(-4) M.

Adenylyl Cyclases↗
PubMed1992

Quality-of-life changes and psychiatric and neurocognitive outcome after heart and liver transplantation.

A prospective study compared psychiatric, neurocognitive, and quality-of-life changes of heart and liver transplant patients. The 51 heart and 61 liver transplant candidates and recipients completed the Beck depression inventory (BDI), state-trait anxiety inventory (STAI), sickness impact profile (SIP), mini-mental state (MMS), California verbal learning test (CVLT), Wisconsin card sorting test (WCST), trailmaking test (TMT), and the impact message inventory (IMI). Data were gathered before transplant and at 3-month intervals for up to 1 year after transplant. Psychometric tests scores were correlated with electroencephalograms for the liver patients. Both groups showed significant improvements after transplant in neurocognitive functioning, depressive symptoms, and quality of life.

Adult↗
PubMed1992

The importance of bicarbonate in large volume anesthetic preparations. Revisiting the tumescent formula.

BACKGROUND: The tumescent local anesthetic approach is now being used more widely in dermatologic surgery. Although the original formula contains 12.5 mEq sodium bicarbonate per 50 mL of lidocaine, traditionally buffered solutions contain 1 mEq per 10 mL. OBJECTIVE: This study examines the effects of changing the concentrations of sodium bicarbonate in the tumescent formula. METHODS: Various concentrations of sodium bicarbonate in tumescent anesthetic preparations were measured for pH. RESULTS: Tumescent anesthetic preparations containing 5 mEq/L have a more physiologic pH (7.41) than the classic formula of 12.5 mEq/L (7.73). Clinical use of this reduced sodium bicarbonate solution showed no difference from the original formula. CONCLUSIONS: Sodium bicarbonate can be used in a 1 mEq per 10 mL of lidocaine ratio similar to other buffered anesthetic solutions. This solution is physiologic in pH. However, some thought should also be given to the pKa of lidocaine, which is at pH 7.9. To achieve this even higher concentration (20 mEq/L) bicarbonate must be added to the tumescent solution. Thought must be given to these concepts when tumescent solutions are used in large volumes.

Anesthesia, Local↗
PubMed1992

Phosphatidylcholine composition of endotracheal tube aspirates of neonates and subsequent respiratory disease.

The phosphatidylcholine (PC) content of the initial endotracheal tube aspirate was measured in 105 infants intubated for resuscitation or for ventilation for respiratory distress syndrome, using high performance liquid chromatography and postcolumn fluorescence derivitization with diphenyl-1,3,5-hexatriene. Sixty eight had measurable PC. Of the infants who developed respiratory distress syndrome, with or without subsequent chronic lung disease, neither the percentage of dipalmitoylphosphatidylcholine (DPPC) nor the ratio of DPPC to palmitoyloleoylphosphatidylcholine (POPC), showed any correlation with gestational age. However, both parameters were significantly lower overall in this group than in the group of infants who did not develop respiratory distress syndrome. Infants with a ratio of DPPC:POPC less than 3.0 developed respiratory distress syndrome irrespective of gestational age, but there was considerable overlap between groups for values greater than this. The infants with respiratory distress syndrome who went on to develop chronic lung disease had the same initial PC profile as those with respiratory distress syndrome who did not develop chronic lung disease, but differed as a group by being lighter and more premature. The development of chronic lung disease was not associated with a particular initial PC composition. Other factors related to increasing prematurity must therefore be involved in rendering infants vulnerable to developing chronic lung disease.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Tympanic electrocochleography: normal and abnormal patterns of response.

Electrocochleography has been widely used in human and animal studies of endolymphatic hydrops. A variety of response patterns have been reported in normal and hydropic ears. Recent clinical studies have focused almost exclusively on the amplitude ratio of the summating potential (SP) and action potential (AP) derived from alternating polarity click responses. In this report normal response patterns are described with a tympanic membrane electrode employing condensation, rarefaction and alternating polarity clicks and tone burst stimulation. A variety of response abnormalities are described in patients with suspected endolymphatic hydrops. The exclusive use of alternating polarity clicks is not adequate to reveal the nature of these abnormalities.

Acoustic Stimulation↗
PubMed1992

Liver transplantation.

Liver transplantation is indicated for many patients with irreversible end-stage liver disease. This article discusses patient evaluation and selection, causes of end-stage liver disease, donor liver recovery, the transplant surgical procedure, and acute postoperative care of the adult liver transplant recipient.

Humans↗
PubMed1991

The 21-aminosteroid antioxidant tirilazad mesylate, U-74006F, blocks cortical hypoperfusion following spreading depression.

Cortical spreading depression (SD) has been implicated in the pathophysiology of classical migraine headache and cerebral ischemia. A reduction in cerebral blood flow (CBF), mimicking that seen during the aura and headache phase of migraine, is typically observed following SD in the rat. This phenomenon may also play a role in potentiating ischemic brain damage. In the present study, brief cortical exposure to 1 M KCl produced a marked suppression of EEG amplitude which persisted 20 min in the rat. Upon normalization of the EEG, cortical blood flow declined 20-30% and remained low for at least 2 h. Treatment with a 1 mg/kg i.v. dose of the 21-aminosteroid antioxidant tirilazad mesylate (U-74006F), 2 min following KCl application, completely blocked the hypoperfusion while leaving the magnitude and duration of the EEG suppression and mean arterial pressure unchanged. Tirilazad mesylate is a potent inhibitor of oxygen radical-mediated lipid peroxidation both in vitro and in vivo. Thus, based on present results, an oxygen radical hypothesis is proposed to account for the SD-induced cerebral hypoperfusion.

Animals↗
PubMed1991

Regulation of cytochrome P-450 dependent steroid hydroxylase activity in Manduca sexta: effects of the ecdysone agonist RH 5849 on ecdysone 20-monooxygenase activity.

The non-steroidal ecdysone agonist RH 5849 (1,2-dibenzoyl-1-tert-butylhydrazine) was found to inhibit in a dose-response and apparently competitive fashion the cytochrome P-450 dependent ecdysone 20-monooxygenase activity in the midgut of wandering stage last instar larvae of the tobacco hornworn, Manduca sexta. More effectively on a per molar basis than the naturally occurring molting hormones ecdysone and 20-hydroxyecdysone, RH 5849 was also found to elicit the dramatic 50-fold increase in midgut steroid hydroxylase activity (which normally occurs with the onset of the wandering stage) when injected into competent head or thoracic ligated pre-wandering last instar larvae. These data support and extend the potential usefulness of RH 5849 as a pharmacological probe for further investigating the actions of ecdysteroids and their role(s) in the regulation of ecdysteroid monooxygenases.

Animals↗
PubMed1991

Metrical variation in the thumb, index, and middle finger among four samples of both sexes.

Metrical length and width parameters of the first through third ray metacarpals and phalanges are presented for four samples of adults of both sexes drawn from radiographs of the Ten State Nutrition Survey (1968-1970). Radiographic measurements were obtained with the aid of a digitizer and computer translation program. The establishment of ranges of variation among these samples allows their use in clinical diagnosis, for example of syndromes via pattern profile analysis. Proportional analyses of hand metrics can now be extended to include widths of the first three rays as well as lengths, and data for such a purpose are now available for American blacks. Mexican-Americans, and Oriental-Americans in addition to American white groups. Examples of intersample variation are given; the need to consider such variation in clinical contexts is emphasized.

Adult↗
PubMed1991

Application of image analysis to neurological screening through figure-copying tasks.

Approaches to the detection and monitoring of neurological dysfunction are generally resource-intensive and often difficult to evaluate objectively. This paper describes an approach to neurological screening which is based on the on-line analysis of figure copying tasks, and a variety of features are measured to characterise task execution. It is shown how both qualitative and quantitative measures of individual performance can be obtained in real time. A preliminary experimental study is described to identify appropriate performance indicators for a reference asymptomatic population and for a population with a known abnormal clinical history. The results obtained experimentally demonstrate that the approach proposed, while convenient and efficient in terms of the resources required in implementation, nevertheless offers a high degree of robustness and sensitivity which supports an optimistic view of its clinical viability.

Adolescent↗
PubMed1991

Acetaldehyde and microtubules.

Acetaldehyde covalently binds to tubulin to form stable and unstable adducts. Although tubulin has numerous lysine residues available to react with acetaldehyde, a key highly reactive lysine (HRL) on the alpha chain appears to be a preferential target for stable binding. The HRL residue is available for selective binding when tubulin is in the free (dimer) state but not when it is in the polymerized (microtubule) state. Stable binding of acetaldehyde to the HRL residue markedly inhibits tubulin assembly into microtubules, whereas stable binding to other residues (bulk adducts) has little influence on assembly. Substoichiometric stable binding of acetaldehyde to the HRL is sufficient to inhibit polymerization, via direct interference of tubulin dimer-dimer interactions, and an HRL adduct on only one out of 20 tubulin molecules can totally inhibit polymerization. These findings, along with our previous studies demonstrating impaired microtubule-dependent protein trafficking pathways in livers of ethanol-fed animals, indicate that low acetaldehyde concentrations, formed during ethanol oxidation in vivo, could generate sufficient amounts of HRL adducts on the alpha chain of tubulin in cellular systems to alter microtubule formation and function. In addition to alpha-tubulin, calmodulin and actin have also been found to have enhanced reactivity toward acetaldehyde. Thus, a general hypothesis to describe cellular injury induced by acetaldehyde adducts can be formulated: during ethanol oxidation, acetaldehyde forms stable adducts via binding to reactive lysine residues of preferential target proteins, resulting in selective functional impairment of these proteins and ultimately leading to cellular injury.

Acetaldehyde↗
PubMed1991

In vivo and in vitro characterization of mesothelial lipid inclusions.

The nature of intracytoplasmic lipid inclusions found in cultured rabbit and rat peritoneal mesothelial cells was examined by ultrastructural and biochemical techniques. Transmission electron microscopy also demonstrated extracellular release of these lipid bodies. Differential fixation with tannic acid revealed 2 types of inclusions, lamellated (lamellar bodies) and nonlamellated (homogeneous). The lamellar bodies were found near or in the Golgi apparatus and on the cell surface where occasionally they were observed in exocytotic pouches. The homogeneous inclusions were the predominant species being found primarily intracellularly. Lipid bodies obtained from the culture media over the cells displayed on electron microscopy the same morphological characteristics as those seen intracellularly. Exposure of confluent cultures of mesothelial cells to the vital lipid stain Nile Red caused the appearance of intensely fluorescent droplets in or on the cells at wave lengths consistent with staining for phosphatidylcholine-rich vesicles. Incubation of the cells with (14C)-choline and subsequent analysis of phospholipid formation revealed high rates of (14C)-phosphatidylcholine addition to both intra- and extracellular lipid pools. Taken together, mesothelial cells exhibit lipid bodies similar in ultrastructure to the surfactant containing organelles of Type II pneumocytes.

Animals↗
PubMed1991

Comparison of the efficacy of mechanistically different antioxidants in the rat hemorrhagic shock model.

Four pharmacological mechanisms for antagonizing free radical generation or reactions were compared in terms of their efficacy in attenuating hemorrhagic shock in rats. These included opposing superoxide generation by xanthine oxidase (e.g., oxypurinol), inhibiting arachidonic acid oxidation by cyclooxygenase (e.g., ibuprofen), chelating iron (e.g., desferal), and inhibiting lipid peroxidation (e.g., tirilazad mesylate [U-74006F] and U-78517G). Animals were hemorrhaged to a mean arterial pressure (MAP) of 43-45 mmHg where they were held for 2 hr. Five minutes prior to the end of the hemorrhage period, either vehicle, U-74006F (10 mg/kg), U-78517G (10 mg/kg), oxypurinol (10 or 25 mg/kg), desferal (10 or 25 mg/kg), or ibuprofen (10 mg/kg) was administered i.v., followed by the reinfusion of shed blood. In vehicle-treated animals, MAP declined progressively over the 2 hr post-reinfusion. Ibuprofen, desferal, and oxypurinol treatments each failed to attenuate this decline. In contrast, both U-74006F and U-78517G resulted in a significantly improved maintenance of MAP. Evidence of shock-induced lipid peroxidation was observed in terms of a 73.8% depletion in liver vitamin E content at 2 hr post-reinfusion in vehicle-treated rats. This decrease was prevented by both U-74006F and U-78517G. Inhibition of free radical-induced lipid peroxidation appears more effective for attenuating free radical pathophysiology in hemorrhagic shock that attempting to inhibit specific pathways of oxygen radical generation.

Animals↗
PubMed1991

U-78517F: a potent inhibitor of lipid peroxidation with activity in experimental brain injury and ischemia.

U-78517F (2-[4-[2,6-di-(1-pyrrolidinyl)-4-pyridinyl)-1-piperazinyl] methyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, dihydrochloride), which combines the antioxidant ring portion of alpha-tocopherol together with the amine of the previously described 21-aminosteroids (e.g., U-74006F), is a novel inhibitor of iron-catalyzed lipid peroxidation. U-78517F was found to have a 50% inhibitory concentration (IC50) of 0.6 microM against 200 microM ferrous chloride-initiated lipid peroxidation in rat brain homogenates, compared to 8 microM for U-74006F, 28 microM for alpha-tocopherol and 43 microM for the ring portion of alpha-tocopherol (i.e., trolox). Both stereoisomers of the racemic U-78517F proved to be equally active antioxidants. Against lipid peroxidation initiated by xanthine/xanthine oxidase, U-78517F was even more potent, with an IC50 of 0.01 microM. U-78517F was also observed to protect cultured mouse spinal neurons against iron-induced damage, with an IC50 of approximately 0.5 microM. When administered to male CF-1 mice i.v. at 5 min after a severe concussive head injury. U-78517F produced a dose-related improvement in the 1-hr neurological recovery. The minimum effective i.v. dose was 1.0 micrograms/kg. Measurement of U-78517 concentrations in the brains of mice after administration of a 10-mg/kg i.v. dose revealed effective antioxidant levels for as long as 2 hr. Evidence of an in vivo antioxidant action was provided by the attenuation of iron-induced blood-brain barrier disruption (i.e., Evans' blue extravasation) in rats pretreated with U-78517F.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Establishing reliability of biomechanical data using univariate and multivariate approaches.

The purpose of this study was to use generalizability theory with both univariate and multivariate approaches to examine reliability of total body center of mass (CM) values calculated from cinematographical data. Twenty-eight college-aged male volunteers were filmed by a LOCAM camera at 100 fps while performing the basic locomotion skill of walking. Film analysis was conducted on each subject using six frames of film depicting a one-stride walking cycle consisting of right heel strike, right foot flat, left toe-off, left heel strike, left foot flat, and right toe-off. Nineteen segmental endpoints and a reference point were digitized by three experienced plotters. The digitizing sequence was replicated three times by each plotter. A FORTRAN program calculated nine CM values (three plotters by three repetitions) for each subject filmed in each of the six positions of the stride. The x- and y-coordinates of the CM values were the dependent variables analyzed by fully crossed 3-way univariate and multivariate ANOVAs (subjects by plotters by repetitions). All measurement facets were considered to be random. Results indicate that there was very little repetition error but considerable interplotter error for most frames. Phi-coefficients for x- and y-coordinates, separately, fluctuated across frames. The univariate values for the x-coordinates were similar but slightly less than the multivariate values. The Phi-coefficients for Y, however, were considerably lower than the multivariate values. The multivariate Phi-coefficients for generalizing over three plotters and three repetitions ranged from .82 to .90.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Strain-gauge fontanometry--an advance in non-invasive intracranial pressure measurement.

The validation of a fontanometer based on the strain-gauge principle is described. Fontanelle pressures correlated well with invasively determined cerebrospinal fluid (CSF) pressures in a group of neonates and infants with hydrocephalus. This device, which can be zeroed in vivo, has the additional advantage of a fast response time and allows reliable measurements of spontaneous pulsations and induced changes in CSF pressure. Unlike previously reported devices, the accuracy of this transducer was shown to be independent of external forces.

Humans↗