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S A Sanders

Publications and source records attributed to S A Sanders.

14 recordsLinked to original sources
PubMed1992

Characterisation of a haem active-site mutant of horseradish peroxidase, Phe41----Val, with altered reactivity towards hydrogen peroxide and reducing substrates.

A horseradish peroxidase variant ([F41V] HRP-C*), in which Val replaces the conserved Phe at position 41 adjacent to the distal His, has been constructed. Its composition and spectroscopic, catalytic and substrate-binding properties were compared with those of the wild-type recombinant (HRP-C*) and plant (HRP-C) enzymes. Presteady-state kinetic measurements of the rate constant for compound I formation (k1) revealed an eightfold decrease in the reactivity of the Phe41----Val variant towards H2O2, in comparison with HRP-C or HRP-C*. Measurement of the remaining rate constants, k2 and k3, for the two single-electron reduction reactions of [F41V] HRP-C with para-aminobenzoic acid as reducing substrate, showed that they were 2.5-fold and 1.3-fold faster, respectively. In contrast, analysis of data from steady-state assays with 2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonate) as reducing substrate, showed decreased reactivity of the mutant enzyme to this compound, indicating a change in substrate specificity. Over the substrate range studied, the data for HRP-C* and for [F41V] HRP-C conformed to a simple modification of the accepted peroxidase mechanism in which a first-order step (ku), assumed to be product dissociation, becomes rate-limiting under our standard assay conditions. Calculations of rate constants from steady-state data yielded values of k1 for both enzyme forms in adequate agreement with those from pre-steady state measurements. They showed, furthermore, that both k3 for 2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonate) and ku were substantially decreased, fivefold and tenfold, respectively, in the mutant. Analogous to the decrease in ku, we observed a twofold increase in the affinity of the mutant variant for the inhibitor benzhydroxamic acid. The coordination-state equilibrium of the haem iron also appeared shifted towards the hexacoordinate high-spin form. These observations indicate that in addition to affecting reactivity to H2O2, mutations in the distal region and close to the haem iron also affect reactivity towards different reducing substrates, inducing perturbations in the neighbourhood of the aromatic-substrate-binding site, known to be 0.8-1.2 nm from the haem iron.

Amino Acid Sequence↗
PubMed1992

Structural studies by proton-NMR spectroscopy of plant horseradish peroxidase C, the wild-type recombinant protein from Escherichia coli and two protein variants, Phe41----Val and Arg38----Lys.

Wild-type recombinant horseradish peroxidase isoenzyme C and two protein variants, Phe41----Val and Arg38----Lys, have been characterised using both one- and two-dimensional NMR spectroscopy. Proton NMR spectra recorded in both resting and cyanide-ligated states of the proteins were compared with those of the corresponding plant peroxidase. The latter contains 18% carbohydrate in eight N-linked oligosaccharide side chains whereas the recombinant proteins are expressed in nonglycosylated form. The spectra of the plant enzyme and refolded recombinant protein are essentially identical with the exception of carbohydrate-linked resonances in the former, indicating that their solution structures are highly similar. This comparison also identifies classes of carbohydrate resonances in the plant enzyme which provides new information on the local environment and mobility of the oligosaccharide side chains. Comparison of the spectra of the cyanide-ligated states of the two variants and those of plant horseradish peroxidase C indicated that there were significant differences with respect to haem and haem-linked resonances. These could not be rationalised simply on the basis of the local perturbation expected from a single-site substitution. The two substitutions made to residues on the distal side of the haem apparently influenced the degree of imidazolate character of the proximal His170 imidazole ring thus perturbing the magnetic environment of the haem group. Inspection of the spectra of the Phe41----Val variant also showed that the resonances of a phenylalanine residue in the haem pocket had been incorrectly assigned to Phe41 in a previous study. A new assignment, based on additional information from two-dimensional nuclear Overhauser enhancement spectroscopy, was made to Phe152. The assignments made for the Phe41----Val variant were also used as a basis to investigate the structure of the complex formed with the aromatic donor molecule, benzhydroxamic acid.

Arginine↗
PubMed1992

Effects of prenatal exposure to diethylstilbestrol (DES) on hemispheric laterality and spatial ability in human males.

Ten males exposed to diethylstilbestrol (DES), a nonsteroidal synthetic estrogen, during gestation were compared to their matched, unexposed brothers on measures of brain hemispheric specialization for processing nonlinguistic spatial information and cognitive abilities. DES exposure was associated with reduced hemispheric laterality and lowered spatial ability. These data provide direct evidence of a relationship between brain laterality, spatial cognitive ability, and prenatal exposure to hormones in human males. Further, the implications of these findings for understanding sexual differentiation of the human brain are discussed.

Adolescent↗
PubMed1991

Hormonal contributions to sexually dimorphic behavioral development in humans.

Nineteen studies on the behavioral effects of prenatal exposure to hormones administered for the treatment of at-risk human pregnancy are reviewed. Because the role of prenatal exposure to hormones in the development of human behavioral sex differences is potentially confounded by society's differential treatment of the sexes, comparisons between exposed and unexposed subjects were evaluated and summarized separately for male and female subjects. Therefore, this review focuses on data for individuals whose prenatal hormone environments were atypical relative to what is normal for their own sex. Overall, it appears that prenatal exposure to androgen-based synthetic progestin exerted a masculinizing and/or defeminizing influence on human behavioral development, whereas prenatal exposure to natural progesterone and progesterone-based synthetic progestin had a feminizing and/or demasculinizing influence, particularly among female subjects. The data on prenatal exposure to synthetic estrogen derive primarily from subjects exposed to diethylstibestrol (DES). DES-exposed male subjects appeared to be feminized and/or demasculinized, and there is some evidence that exposed female subjects were masculinized. These findings are discussed in the context of prenatal hormonal contributions to sexually dimorphic behavioral development both within and between the sexes. Recommendations for the conduct of future research in developmental behavioral endocrinology are presented.

Behavior↗
PubMed1986

A test of sex differences in aggressive response to hypothetical conflict situations.

Male (n = 289) and female (n = 268) college students were administered the Leifer-Roberts Response Hierarchy (Reinisch Revision) to evaluate the utility of this measure in reflecting sex differences in self-described potential for aggressive response. The Response Hierarchy provides a retrospective estimate of where physical and verbal aggression reside in an individual's hierarchy of possible behavioral responses to hypothetical conflict situations in adolescence. A score is obtained for: (a) physical aggression, (b) verbal aggression, (c) nonaggressive coping, and (d) withdrawal. When asked to respond as they would have or did at age 13 years, verbal aggression was the most frequent response with no significant sex difference in mean scores. Men selected physical aggression significantly more often than women (p less than .001). Using the binomial effect size display (BESD) to illustrate the magnitude of the sex difference, 69% of the men would be classified as physically aggressive (above the median), whereas only 31% of the women would be so classified. It was concluded that the Response Hierarchy consistently demonstrates sex differences among college students in retrospectively reported preference for choosing physical aggression versus other coping strategies as a response to hypothetical interpersonal conflict situations of adolescence.

Adaptation, Psychological↗
PubMed1984

Herpes simplex encephalitis.

This is an acute necrotizing encephalitis with a high mortality rate. It is thought to occur by the reactivation of herpes simplex virus type 1 from latently infected trigeminal ganglia, with subsequent centripetal spread and fulminant growth in tissue of the central nervous system. Prompt diagnosis and antiviral therapy are required because of the rapidly progressive nature and severe consequences of this disease. The physician must understand the pathophysiology to fully appreciate the need for early diagnosis and the gravity of mismanagement.

Acute Disease↗
PubMed1983

Palatability and meal patterns.

Investigations of palatability have often been confounded by nutritional, pharmacological or methodological problems. The present experiment examined the free-feeding meal patterns of two differentially preferred yet nutritionally equivalent diets. When the two diets were offered sequentially (Experiment 1), no differences were found in meal frequency, meal size, or meal duration. However, when the diets were offered simultaneously in Experiment 2, the preferred diet was consumed more frequently, in larger meals, and at a faster feeding rate than the less preferred diet. Further, the meal patterns in Experiment 2 of the preferred diet were identical with those found for both diets in Experiment 1. Therefore, the meal patterns of two diets with differing palatability depend upon the method of presentation with differences appearing when the diets are offered simultaneously but not when they are offered sequentially.

Animals↗
PubMed1982

Early barbiturate exposure: the brain, sexually dimorphic behavior and learning.

Barbiturates, one of the most widely prescribed and abused classes of drugs, reportedly have been prescribed in as many as 25% of pregnancies in the U.S. and Europe over the last 30 years. Nevertheless, there exists little if any data on long-term consequences of prenatal exposure to barbiturates in humans. Evidence from laboratory animals indicates that exposure to barbiturates during early developmental periods results in abnormal neural and biochemical differentiation of the central nervous system, deficits in learning, retarded attainment of developmental milestones, alteration of behavioral and physiological sex differences, increased activity, and decreased responsiveness to aversive and appetitive stimuli. Barbiturates appear to influence the brain via two routes: (1) by direct action on neural tissue; and (2) indirectly by altering hepatic metabolism of steroid hormones. It is concluded that prenatal exposure to barbiturates in human subjects may lead to learning disabilities, decreased IQ, performance deficits, increased incidence of psychosocial maladjustment, and demasculinization of gender identity and sex role behavior in males.

Animals↗
PubMedDate not supplied

High-risk sexual behavior among heterosexual undergraduates at a midwestern university.

Approximately 80% of a self-selected sample of 593 heterosexual undergraduate college students studied at a large Midwestern state university in 1988 had ever experienced penile-vaginal or penile-anal intercourse. One-fifth of the 477 sexually experienced women and men said they had had heterosexual and intercourse. The mean age at first vaginal intercourse was 17, while the mean age at first anal intercourse was about 18.5. Although less than four years, on average, had elapsed since the respondents' first vaginal or anal intercourse, females reported having had an average of 5.6 sexual partners, and males reported an average of 11.2 partners.

Adolescent↗
PubMedDate not supplied

Development of a tool to measure subjective time experience.

Although variations in time experience in specific health-illness situations have been documented, the information has not been systematically described. This is due in part to lack of reliable and valid measurement of time experience. This article, which reports the development and testing of Time Experience Scales (TES) in a sample of healthy adults, represents preliminary work in the identification of temporal experience in ill persons. Subjective time experience was defined as thoughts and feelings about the temporal frame in which life events occur. Semantic differential and Likert scale items indicated four conceptual dimensions of subjective time experience. A mail questionnaire was distributed to a purposive sample of community-based healthy adults. Data were analyzed separately for men (n = 587) and women (n = 475). Factor analysis methods resulted in the emergence of six robust empirical factors: meaning, fast tempo, slow tempo, attention to death, future orientation, and past orientation. Product moment correlations between scales (.01 to .45) indicated the validity, and coefficient alpha (.68 to .88) the reliability of measurement, using the factors. Results suggest that at least six distinct temporal experiences help people assign order, rhythm, and meaning to life events, thereby creating a continuing and optimal life story. Further reliability and validity testing is suggested.

Adolescent↗