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Biomedical subjects

S S Smith

Publications and source records attributed to S S Smith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Race/ethnicity and the 2000 census: implications for public health.

OBJECTIVES: This article addresses the potential impact of the revised standards for race and ethnicity on data from the 2000 census and public health data sources, policies, and programs. METHODS: The authors examine the relationship between race/ethnicity and health in selected measures, identify the factors that influence race/ethnicity identification, consider past experience in race/ethnicity reporting, and explore the challenges in understanding and managing the effects of new racial/ethnic categories in various data sets. RESULTS: The multiple-race group seems to compose only a small percentage of the US population and may have little impact on data for single-race groups. Actual effects will vary according to a number of factors, including the size, composition, and geographic distribution of the group. CONCLUSIONS: More research is needed to support a thorough understanding of the reporting of multirace data and the development of techniques for analyzing these data. Given the importance of understanding the relationship between race/ethnicity and health, the ability to produce useful, comparable, and meaningful data is essential.

Censuses↗
PubMed2000

Does brief loss of consciousness affect cognitive functioning after mild head injury?

Loss of consciousness often is considered an important variable when estimating head injury severity. The purpose of this study was to determine if brief loss of consciousness had any effect on the neuropsychological test performance of patients in acute recovery from an uncomplicated mild head injury (N = 195). Three groups of 65 patients were given a brief battery of neuropsychological tests within one week of sustaining a mild head injury. The groups, sorted on the basis of loss of consciousness (i.e., positive, negative, or equivocal), did not differ in age or education. There were no significant differences among the groups on any of the measures of attention, learning, memory, language, or executive functioning.

Journal Article↗
PubMed1999

A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.

BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.

Administration, Cutaneous↗
PubMed1999

The epidemiology of tobacco use, dependence, and cessation in the United States.

Tobacco use, primarily in the form of cigarette smoking, is the leading preventable cause of death in the United States. After epidemic increases in current smoking in the first half of the 20th century, overall rates of smoking have decreased during the past 30 years. Certain sociodemographic groups continue to have high rates of tobacco use. The prevalence of current smoking in adults in the United States decreased from 42.4% in 1965 to 24.7% in 1995. Recent epidemiologic data indicate that 47 million adults currently smoke cigarettes and over 5 million use smokeless tobacco; over 3 million adolescents are current smokers and over 750,000 use smokeless tobacco. Thus, tobacco use continues to be a major public health concern.

Adolescent↗
PubMed1999

Gender differences in smoking cessation.

Gender differences in smoking quit rates are frequently reported and are the subject of much speculation. This study examined the generalizability of gender differences in abstinence across study sites, treatments, and time of relapse, as well as potential mediators and moderators of gender effects. Participants were smokers who participated in 3 randomized clinical trials of the nicotine patch (N = 632). Men had higher cessation rates than women at all follow-ups. The impact of gender on abstinence was unaffected by controlling for study site, treatment, or time of relapse. There was little evidence for mediation or moderation of this relation by any of a host of predictor variables. The magnitude and consistency of the gender differential, coupled with an inability to account for it, highlights a compelling need for additional research specifically aimed at elucidating the relation between gender and abstinence.

Administration, Cutaneous↗
PubMed1999

Development and validation of the Wisconsin Smoking Withdrawal Scale.

The accurate assessment of nicotine withdrawal is important theoretically and clinically. A 28-item scale, the Wisconsin Smoking Withdrawal Scale, was developed that contains 7 reliable subscales tapping the major symptom elements of the nicotine withdrawal syndrome. Coefficients alpha for the subscales range from .75 to .93. This scale is sensitive to smoking withdrawal, is predictive of smoking cessation outcomes, and yields data that conform to a 7-factor structure. The 7 scales predicted intratreatment smoking, chi2(7, N = 163) = 15.19, p = .034. Moreover, the questionnaire is sufficiently brief so that it can be used in both clinical and research contexts.

Adult↗
PubMed1999

Cystic fibrosis transmembrane conductance regulator. Physical basis for lyotropic anion selectivity patterns.

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel exhibits lyotropic anion selectivity. Anions that are more readily dehydrated than Cl exhibit permeability ratios (P(S)/P(Cl)) greater than unity and also bind more tightly in the channel. We compared the selectivity of CFTR to that of a synthetic anion-selective membrane [poly(vinyl chloride)-tridodecylmethylammonium chloride; PVC-TDMAC] for which the nature of the physical process that governs the anion-selective response is more readily apparent. The permeability and binding selectivity patterns of CFTR differed only by a multiplicative constant from that of the PVC-TDMAC membrane; and a continuum electrostatic model suggested that both patterns could be understood in terms of the differences in the relative stabilization of anions by water and the polarizable interior of the channel or synthetic membrane. The calculated energies of anion-channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19. The model predicts that large anions, like SCN, although they experience weaker interactions (relative to Cl) with water and also with the channel, are more permeant than Cl because anion-water energy is a steeper function of 1/r than is the anion-channel energy. These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative. This simple selectivity mechanism that governs permeability and binding acts to optimize the function of CFTR as a Cl filter. Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by "sticking" within the channel.

Algorithms↗
PubMed1999

CFTR: mechanism of anion conduction.

CFTR: Mechanism of Anion Conduction. Physiol. Rev. 79, Suppl.: S47-S75, 1999. - The purpose of this review is to collect together the results of recent investigations of anion conductance by the cystic fibrosis transmembrane conductance regulator along with some of the basic background that is a prerequisite for developing some physical picture of the conduction process. The review begins with an introduction to the concepts of permeability and conductance and the Nernst-Planck and rate theory models that are used to interpret these parameters. Some of the physical forces that impinge on anion conductance are considered in the context of permeability selectivity and anion binding to proteins. Probes of the conduction process are considered, particularly permeant anions that bind tightly within the pore and block anion flow. Finally, structure-function studies are reviewed in the context of some predictions for the origin of pore properties.

Amino Acid Sequence↗
PubMed1998

Progesterone withdrawal. II: insensitivity to the sedative effects of a benzodiazepine.

Previous results from this lab have demonstrated that the GABA-modulatory steroid 3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) exhibits withdrawal properties, increasing anxiety [M.A. Gallo, S.S. Smith, Progesterone withdrawal decreases latency to and increases duration of electrified prod burial: a possible rat model of PMS anxiety, Pharmacol. Biochem. 46 (1993) 897-904.] and seizure susceptibility [S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J. M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.] upon abrupt discontinuation after chronic administration of its parent compound, progesterone (P), in a manner similar to other GABA-modulatory drugs. Further, we have demonstrated that withdrawal from P produces insensitivity to the potentiating effects of the benzodiazepine (BDZ) lorazepam (LZM) on GABA-gated Cl- current [A.-M.N. Costa, K.T. Spence, S.S. Smith, J.M. H. ffrench-Mullen, Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to BDZ modulation in rats CA1 hippocampus, J. Neurophysiology 74 (1995) 464-469; S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J.M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.], assessed using whole cell patch clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. The purpose of the present study was to examine the withdrawal effects of P on the sedative potency of LZM, tested behaviorally as the ability to maintain position on a variable speed treadmill following LZM administration (0.75 mg/kg). Both continuous (continuous release P capsule, single withdrawal) as well as discontinuous (multiple P injection, multiple withdrawal) paradigms were tested. Longer continuous release paradigms were more effective in abolishing the sedative effects of LZM, without producing a change in baseline response. The LZM insensitivity observed following the multiple withdrawal paradigm was prevented by prior intraventricular administration of antisense oligonucleotide against the alpha4 subunit of the GABAA receptor. These results support the hypothesis that withdrawal from P decreases the behavioral response to LZM as a direct result of increases in the alpha4 subunit of the GABAA receptor. Withdrawal from P occurs endogenously during pre-menstrual and post-partum periods, when decreased response to BDZ has been reported.

Analysis of Variance↗
PubMed1998

Progesterone withdrawal I: pro-convulsant effects.

Pro-convulsant withdrawal properties have been reported for a variety of GABA-modulatory drugs, such as the benzodiazepines (BDZs, [S.E. File, The history of BDZ dependence: a review of animal studies, Neurosci. Biobehav. Rev. 14 (1990) 135-146; P.R. Finley, P. E. Nolan, Precipitation of BDZ withdrawal following sudden discontinuation of midazolam, DICP 23 (1989) 151-152]), barbiturates and ethanol [N. Kokka, D.E. Sapp, U. Witte, R.W. Olsen, Sex differences in sensitivity to pentylenetetrazol but not in GABAA receptor binding, Pharm. Biochem. Behav. 43 (1992) 441-447]. In this report, we test the hypothesis that pro-convulsant effects are produced by withdrawal from the GABA-modulatory neurosteroid 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) after sustained exposure to elevated circulating levels of its parent compound progesterone (P). Seizure activity was precipitated by picrotoxin or with the BDZ inverse agonist n-methyl-beta-carboline-3-carboxamide (beta-CC), and a seizure rating determined 24 h after abrupt discontinuation of P following a multiple withdrawal/chronic administration paradigm. In some cases, a pseudopregnant rat model was employed to produce increased ovarian production of P prior to withdrawal (ovariectomy). Rats undergoing P withdrawal exhibited greater seizure-like activity than vehicle-treated controls, and received seizure scores in the same range as rats undergoing BDZ withdrawal. Administration of a 5alpha-reductase blocker, MK-906, along with P, prevented this pro-convulsant effect of P withdrawal, suggesting that the GABA-modulatory 3alpha,5alpha-THP is the active compound responsible for this withdrawal effect. Combined administration of P and diazepam produced synergistic effects upon withdrawal and produced a seizure score higher than observed after withdrawal from either agent alone. These results suggest that P exhibits withdrawal properties via the neuroactive steroid 3alpha, 5alpha-THP, that include exacerbation of seizure activity. These results may have clinical relevance, as increased incidence and severity of seizures has been reported in susceptible women during times of declining circulating levels of P across the menstrual cycle [T. Backstrom, B. Zetterlund, S. Blom, M. Romano, Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with partial epilepsy, Acta Neurol. Scand. 69 (1984) 240-248; A.G. Herzog, Progesterone therapy in women with complex partial and secondary generalized seizures, Neurology 45 (1995) 1660-1662].

Animals↗
PubMed1998

Withdrawal from 3alpha-OH-5alpha-pregnan-20-One using a pseudopregnancy model alters the kinetics of hippocampal GABAA-gated current and increases the GABAA receptor alpha4 subunit in association with increased anxiety.

In the present study, we have characterized properties of steroid withdrawal using a pseudopregnant rat model. This paradigm results in increased production of endogenous progesterone from ovarian sources and as such is a useful physiological model. "Withdrawal" from progesterone induced by ovariectomy on day 12 of pseudopregnancy resulted in increased anxiety, as determined by a decrease in open arm entries on the elevated plus maze compared to control rats and pseudopregnant animals not undergoing withdrawal. Similar findings were obtained 24 hr after administration of a 5alpha-reductase blocker to a pseudopregnant animal, suggesting that it is the GABAA-modulatory 3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) that produces anxiogenic withdrawal symptoms. Twenty-four hours after steroid withdrawal, the time constant for decay of GABAA-gated current was also reduced sixfold, assessed using whole- cell patch-clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. Thus, 3alpha,5alpha-THP withdrawal results in a marked decrease in total GABAA current, a possible mechanism for its anxiogenic, proconvulsant sequelae. In addition, 3alpha,5alpha-THP withdrawal resulted in insensitivity to the normally potentiating effect of the benzodiazepine lorazepam (LZM) on GABAA-gated Cl- current. This withdrawal profile is similar to that reported for other GABAA-modulatory drugs such as the benzodiazepines (BDZs), barbiturates, and ethanol. These changes were also associated with significant two and threefold increases in both the mRNA and protein for the alpha4 subunit of the GABAA receptor, respectively, in hippocampus. The pseudopregnancy paradigm may be a useful model for periods of endogenous 3alpha,5alpha-THP withdrawal such as premenstrual syndrome and postpartum or postmenopausal dysphoria, when increased emotional lability and BDZ insensitivity have been reported.

Animals↗
PubMed1998

GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid.

The hormone progesterone is readily converted to 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) in the brains of males and females. In the brain, 3alpha,5alpha-THP acts like a sedative, decreasing anxiety and reducing seizure activity, by enhancing the function of GABA (gamma-aminobutyric acid), the brain's major inhibitory neurotransmitter. Symptoms of premenstrual syndrome (PMS), such as anxiety and seizure susceptibility, are associated with sharp declines in circulating levels of progesterone and, consequently, of levels of 3alpha,5alpha-THP in the brain. Abrupt discontinuation of use of sedatives such as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms. Here we report a progesterone-withdrawal paradigm, designed to mimic PMS and post-partum syndrome in a rat model. In this model, withdrawal of progesterone leads to increased seizure susceptibility and insensitivity to benzodiazepine sedatives through an effect on gene transcription. Specifically, this effect was due to reduced levels of 3alpha,5alpha-THP which enhance transcription of the gene encoding the alpha4 subunit of the GABA(A) receptor. We also find that increased susceptibility to seizure after progesferone withdrawal is due to a sixfold decrease in the decay time for GABA currents and consequent decreased inhibitory function. Blockade of the alpha4 gene transcript prevents these withdrawal properties. PMS symptoms may therefore be attributable, in part, to alterations in expression of GABA(A) receptor subunits as a result of progesterone withdrawal.

Animals↗
PubMed1998

Stalling of human DNA (cytosine-5) methyltransferase at single-strand conformers from a site of dynamic mutation.

Single-strand conformers (SSCs) from the C-rich strand of the triplet repeat at the FMR-1 locus are rapidly and selectively methylated by the human DNA (cytosine-5) methyltransferase. The apparent affinity of the enzyme for the FMR-1 SSC is about tenfold higher than it is for a control Watson-Crick paired duplex. The de novo methylation rate for the SSC is over 150-fold higher than the de novo rate for the control duplex. Methylation of what is generally called a hemi-methylated duplex occurs with a rate enhancement of over 100-fold, while methylation of what can be viewed as a hemi-methylated FMR-1 SSC is actually slower than the de novo rate. The pronounced inhibition of the methyltransferase by the methylated SSC suggests that the enzyme has a higher affinity for the methylated product of its reaction with the SSC than it has for the unmethylated SSC substrate. Gel retardation studies show that the methyltransferase binds selectively to SSCs from the C-rich strand of the FMR-1 triplet repeat. This suggests a two-step stalling process in which the human methyltransferase first selectively methlyates and subsequently stalls at the C-rich strand SSC. Stalling may reflect the inability of the enzyme to release a DNA product that is fixed in a conformation resembling its transition state by the unusual structure of the substrate. In particular, the data suggest that DNA methyltransferase may physically participate in biological processes that lead to dynamic mutation at FMR-1. In general, the data raise the possibility that a two-step stalling process occurs at secondary structures associated with chromosome instability, chromosome remodelling, viral replication or viral integration and may account for the local hypermethylation and global hypomethylation associated with viral and non-viral tumorigenesis.

Base Composition↗
PubMed1998

Cystic fibrosis transmembrane conductance regulator (CFTR) anion binding as a probe of the pore.

We compared the effects of mutations in transmembrane segments (TMs) TM1, TM5, and TM6 on the conduction and activation properties of the cystic fibrosis transmembrane conductance regulator (CFTR) to determine which functional property was most sensitive to mutations and, thereby, to develop a criterion for measuring the importance of a particular residue or TM for anion conduction or activation. Anion substitution studies provided strong evidence for the binding of permeant anions in the pore. Anion binding was highly sensitive to point mutations in TM5 and TM6. Permeability ratios, in contrast, were relatively unaffected by the same mutations, so that anion binding emerged as the conduction property most sensitive to structural changes in CFTR. The relative insensitivity of permeability ratios to CFTR mutations was in accord with the notion that anion-water interactions are important determinants of permeability selectivity. By the criterion of anion binding, TM5 and TM6 were judged to be likely to contribute to the structure of the anion-selective pore, whereas TM1 was judged to be less important. Mutations in TM5 and TM6 also dramatically reduced the sensitivity of CFTR to activation by 3-isobutyl 1-methyl xanthine (IBMX), as expected if these TMs are intimately involved in the physical process that opens and closes the channel.

1-Methyl-3-isobutylxanthine↗