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Biomedical subjects

S S Smith

Publications and source records attributed to S S Smith.

At least 91 records · Page 5Linked to original sources

Smoking outcome expectancies: factor structure, predictive validity, and discriminant validity.

Recent models of addiction posit that drug outcome expectancies are influential determinants of drug use. The current research examines the dimensional structure, predictive validity, and discriminant validity of expectancies for cigarette smoking in a prospective study. There was a good fit between the factor structure of the Smoking Consequences Questionnaire and the observed data. In addition, the internal consistency of each scale was satisfactory. Moreover, there was considerable evidence for the predictive and discriminant validity of expectancies. Expectancies of positive outcomes (positive reinforcement, negative reinforcement, and appetite-weight control) predicted withdrawal severity. Negative reinforcement expectancies and expectancies of negative consequences predicted cessation success. Predictive relations remained significant after controlling for related constructs: negative affect, stress, and dependence measures.

Adult↗

Coupled secretion of chloride and mucus in skin of Xenopus laevis: possible role for CFTR.

We used the isolated skin of Xenopus laevis to investigate the relationship between the secretion of salt, water, and mucus by submucosal glands expressing the cystic fibrosis transmembrane conductance regulator (CFTR). In situ hybridization and immunofluorescence provided evidence for specific expression of CFTR in the mucus-secreting cells of the subepidermal glands. Stimulation of isolated sheets of skin with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate produced active Cl secretion and a marked increase in tissue conductance that was correlated with mucous cell degranulation and the distention of the glandular ducts. This coordinated increase in active secretion of salt and mucus was abolished by pretreatment of skins with bumetanide or by removing Cl from the bathing solutions. These results provide evidence for an intimate coupling between electrolyte transport and mucus secretion that may illuminate the pathophysiology of mucus-producing glands in cystic fibrosis lung disease.

Animals↗

Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments.

OBJECTIVE: To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments. DESIGN: Two independent randomized placebo-controlled double-blind trials. SETTING: Smoking cessation clinic. SUBJECTS: Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking. INTERVENTIONS: Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2). MAIN OUTCOME MEASURES: Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving). RESULTS: Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking. CONCLUSION: Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms.

Administration, Cutaneous↗

The effects of athletic massage on delayed onset muscle soreness, creatine kinase, and neutrophil count: a preliminary report.

It was hypothesized that athletic massage administered 2 hours after eccentric exercise would disrupt an initial crucial event in acute inflammation, the accumulation of neutrophils. This would result in a diminished inflammatory response and a concomitant reduction in delayed onset muscle soreness (DOMS) and serum creatine kinase (CK). Untrained males were randomly assigned to a massage (N = 7) or control (N = 7) group. All performed five sets of isokinetic eccentric exercise of the elbow flexors and extensors. Two hours after exercise, massage subjects received a 30-minute athletic massage; control subjects rested. Delayed onset muscle soreness and CK were assessed before exercise and at 8, 24, 48, 72, 96, and 120 hours after exercise. Circulating neutrophils were assessed before and immediately after exercise, and at 30-minute intervals for 8 hours; cortisol was assessed before and immediately after exercise, and at 30-minute intervals for 8 hours; cortisol was assessed at similar times. A trend analysis revealed a significant (p < 0.05) treatment by time interaction effect for 1) DOMS, with the massage group reporting reduced levels; 2) CK, with the massage group displaying reduced levels; 3) neutrophils, with the massage group displaying a prolonged elevation; and 4) cortisol, with the massage group showing a diminished diurnal reduction. The results of this study suggest that sports massage will reduce DOMS and CK when administered 2 hours after the termination of eccentric exercise. This may be due to a reduced emigration of neutrophils and/or higher levels of serum cortisol.

Adult↗

Transition state analogs as affinity labels for human DNA methyltransferases.

A new class of affinity labels has been developed for human DNA (cytosine-5) methyltransferases. These oligodeoxynucleotides contain 5-fluorodeoxycytidine at a mispair within the recognition motif of the human enzyme. They were not effectively recognized by bacterial methyltransferases. They can be viewed as analogs of the intermediates transiently produced by methyltransferases during catalysis. Affinity labelling patterns suggest that both the structurally induced activity and the methyl-directed activity of the human enzymes operate by the same mechanism and reside on the same polypeptide chains.

Affinity Labels↗

Progesterone withdrawal decreases latency to and increases duration of electrified prod burial: a possible rat model of PMS anxiety.

The purpose of this study was to determine whether withdrawal from chronic exposure to the female sex steroid progesterone (P) alters response of female rats to an electrified prod using the defensive burying paradigm, considered a rat model of anxiety. Withdrawal from chronic exposure to 500 micrograms P (daily, SC, for four days) resulted in a significant decrease in the latency (77%, P < 0.05) to prod burial and an increase in duration (75%, P < 0.05) of this reflexive response, compared with the behavior of oil-injected controls. These results are consistent with the idea that withdrawal from chronic exposure to P increases behaviors that accompany anxiety. At a lower dose (50 micrograms), withdrawal from chronically administered P produced significant changes in response to this paradigm only when the steroid was given concomitantly with estradiol (2 micrograms, SC, for two days). Prior exposure to indomethacin, which blocks the conversion of P to its metabolite 3 alpha,5 alpha-tetrahydroprogesterone (3-alpha-hydroxy-5-alpha-pregnan-20-one), prevented P withdrawal from altering response in the defensive burying paradigm. This finding suggests that it may be withdrawal from this metabolite, rather than P, which increases behaviors associated with increased anxiety.

Animals↗

Repetitive motion disorders: the design of optimal rate-rest profiles.

Repetitive motion disorders of the upper extremities are the primary cause of lost time in hand-intensive industries. Typical remedies include the introduction of job aids and the redesign of the job. An alternative approach is considered here. Procedures are developed that can be used to determine the parameters of a job (e.g., the rate of work and the number and duration of the rest breaks) that minimize repetitive motion disorders and maximize productivity. It is shown that in theory the job parameters can be set so that one can achieve not only a decrease in repetitive motion disorders but also an increase in productivity. The application of the procedures to an actual manufacturing job requiring high-repetitive, high-force hand motions is discussed in detail.

Cumulative Trauma Disorders↗

Order effects in the administration of the Booklet Category Test and Wisconsin Card Sorting Test.

In order to evaluate the possibility of significant order effects, the Booklet Category Test and Wisconsin Card Sorting Test were administered in counterbalanced order to 20 psychiatric patients, 36 neurological patients, and 30 healthy, elderly individuals. Administering the Booklet Category Test first improved scores on the Wisconsin Card Sorting Test, although not to a statistically significant degree. Unexpectedly administering the Wisconsin Card Sorting Test first resulted in poorer scores on the Booklet Category Test. The results are discussed in terms of future research and clinical implications.

Journal Article↗

Prevalence of daily and experimental smoking among University of Wisconsin-Madison undergraduates, 1989-1993.

Limited information is available on smoking among college students. This study surveyed smoking prevalence and frequency among University of Wisconsin-Madison undergraduates aged 17 to 22 (n = 6,069) during the years 1989 through 1993. Sampling was conducted before and after the implementation of a smoke-free campus policy. Daily smoking remained constant across the 5 years at just under 10% of the sample; males showed a trend toward increased daily smoking (7.8% to 11.7%), while females showed a declining trend (10.2% to 8.4%). Additionally, 27% engaged in experimental smoking (smoking every few days, weeks, or months), resulting in a disturbing overall rate of tobacco use: about 37% of all students. These data indicate a need for more directed efforts to help university students overcome the threat of tobacco addiction.

Adolescent↗

Novel action of nitric oxide as mediator of N-methyl-D-aspartate-induced phosphatidylinositol hydrolysis in neonatal rat cerebellum.

Nitric oxide (NO) is an intercellular mediator produced within the cerebellum and other central nervous system sites. Results from the present study suggest a novel role for this gaseous second messenger in mediating the stimulatory actions of the excitatory amino acid agonist N-methyl-D-aspartate (NMDA) on turnover of phosphatidylinositol (PI) in the neonatal cerebellum. Activation of the NMDA receptor stimulates PI turnover in developing cerebellum when these neurons are in a depolarized state, but the mechanism underlying this effect is unknown. We measured changes in PI hydrolysis induced by NMDA in the presence of baclofen, which is known to depolarize neurons by activating presynaptic inhibitory gamma-aminobutyric acidB autoreceptors. NMDA increased PI hydrolysis by 80% in the presence of 1 microM baclofen. This modulatory action of NMDA was prevented by two competitive inhibitors of NO synthase, L-NG-monomethylarginine and L-N omega-nitroarginine, as well as by hemoglobin, which binds NO. Inhibition of NMDA-induced PI hydrolysis by L-NG-monomethylarginine was reversed by prior administration of L-arginine (200 microM), the physiological substrate of NO synthase. Arginine (500 microM) alone was also able to increase PI hydrolysis significantly. Superoxide dismutase, which prolongs the half-life of NO, also significantly increased the ability of NMDA to stimulate PI hydrolysis. However, NO-induced activation of the cGMP pathway did not appear to be responsible for the NMDA-induced increase in PI hydrolysis, because addition of 8-bromo-cGMP decreased this parameter, and methylene blue, which blocks guanylate cyclase activity, did not inhibit the PI hydrolysis evoked by NMDA receptor activation. These results suggest that NMDA receptor activation acts to release NO, which then acts through a novel pathway to enhance the hydrolysis of PI in the developing rat cerebellum. This novel role for NO in mediating the stimulatory actions of NMDA on PI hydrolysis may be important for developmental processes in the central nervous system.

Animals↗

Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation.

The properties of the methyl-directed DNA (cytosine-5-)-methyltransferase (EC 2.1.1.37) suggest that it is the enzyme that maintains patterns of methylation in the human genome. Proposals for the enzyme's mechanism of action suggest that 5-methyldeoxycytidine is produced from deoxycytidine via a dihydrocytosine intermediate. We have used an oligodeoxynucleotide containing 5-fluorodeoxycytidine as a suicide substrate to capture the enzyme and the dihydrocytosine intermediate. Gel retardation experiments demonstrate the formation of the expected covalent complex between duplex DNA containing 5-fluorodeoxycytidine and the human enzyme. Formation of the complex was dependent upon the presence of the methyl donor S-adenosylmethionine, suggesting that it comprises an enzyme-linked 5-substituted dihydrocytosine moiety in DNA. Dihydrocytosine derivatives are extremely labile toward hydrolytic deamination in aqueous solution. Because C-to-T transition mutations are especially prevalent at CG sites in human DNA, we have used high-performance liquid chromatography to search for thymidine that might be generated by hydrolysis during the methyl transfer reaction. Despite the potential for deamination inherent in the formation of the intermediate, the methyltransferase did not produce detectable amounts of thymidine. The data suggest that the ability of the human methyltransferase to preserve genetic information when copying a methylation pattern (i.e., its fidelity) is comparable to the ability of a mammalian DNA polymerase to preserve genetic information when copying a DNA sequence. Thus the high frequency of C-to-T transitions at CG sites in human DNA does not appear to be due to the normal enzymatic maintenance of methylation patterns.

Base Sequence↗

Recognition of foldback DNA by the human DNA (cytosine-5-)-methyltransferase.

In order to specify the recognition requirements of the human DNA (cytosine-5-)-methyltransferase, two isomeric 48mers were synthesized so as to link a long block of DNA with a shorter complementary block of DNA through a tether consisting of five thymidine residues. These isomeric foldback molecules, differing only in the location of the 5-methyldeoxycytosine, were shown to be unimolecular, to contain a region of duplex DNA, and to contain a region of single-stranded DNA. When used as substrates for the DNA methyltransferase, only one of the isomers was methylated. A comparison of the structures of the two isomers allows us to begin to define the potential sites of interaction between the enzyme and the three nucleotides forming a structural motif consisting of 5-methyldeoxycytosine, its base-paired deoxyguanosine, and a deoxycytosine 5' to the paired deoxyguanosine.

Base Sequence↗

Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers.

Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.

Alcoholism↗