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Biomedical subjects

S A Mason

Publications and source records attributed to S A Mason.

At least 19 recordsLinked to original sources

Site-directed mutagenesis of the phosphorylation sites in the mouse glucocorticoid receptor.

The functional significance of receptor phosphorylation in mediating the actions of glucocorticoids remains undefined. The identification of seven phosphorylation sites in the mouse glucocorticoid receptor (Bodwell, J. E., Orti, E., Coull, J. M., Pappin, D. J. C., Smith, L. I., and Swift, F. (1991) J. Biol. Chem. 266, 7549-7555) permits a direct examination of the potential regulatory role of glucocorticoid receptor phosphorylation in transactivation. Using oligonucleotide-directed mutagenesis of the mouse glucocorticoid receptor cDNA, we have substituted alanine or aspartate for the residues phosphorylated in this ligand-dependent transcription factor. COS-1 cells were cotransfected with mutant receptor cDNA expression vectors and a reporter plasmid containing the glucocorticoid-inducible mouse mammary tumor virus promoter linked to chloramphenicol acetyltransferase in order to characterize the effect of these substitutions on receptor-mediated gene expression. Substitution of alanine or aspartate at single phosphorylation sites does not prevent receptor transactivation. Receptors containing multiple substitutions of alanine or aspartate at the major phosphorylation sites in the acidic domain elicit levels of hormone-induced reporter gene expression that are comparable to wild-type receptors. Mutant receptors substituted with alanine at the five phosphorylation sites conserved among the rat, human, and mouse receptors exhibit a 22% decrease in transcriptional activity. Receptors mutated at all seven sites display a similar modest reduction. These results demonstrate that receptor phosphorylation at these seven identified residues is not a major determinant in glucocorticoid receptor transcriptional activity at the mouse mammary tumor virus promoter.

Animals

Young, scarred children and their mothers--a short-term investigation into the practical, psychological and social implications of thermal injury to the preschool child. Part I: Implications for the mother.

A short-term, prospective study, using both quantitative and qualitative methods, was designed to determine the practical, psychological and social implications of thermal injury resulting in scarring, for the mothers of thermally injured children, during the 6 months following the child's discharge from hospital. Mothers of 57 thermally injured children under 5 years of age were interviewed whilst the child was in hospital and at home, at 1 week, 2 months and 6 months following hospital discharge. Thermal injuries ranged from 1 to 41 per cent of body surface area and all required skin grafting. Qualitative analysis of interview transcripts resulted in the development of a model of the mother's response--The Maternal Thermal Injury Response Pattern (MTIRP)--which describes a phasic pattern of general response categories. The mothers' psychiatric morbidity was measured using Goldberg's (1978) 60-item General Health Questionnaire (GHQ). The mean of the mothers' total GHQ scores was 2.42 for the retrospective, pre-injury score, 24.5 at the hospital interview and 5.96 at 6 months following the child's discharge from hospital. In conclusion, the mother is a neglected victim of a young child's thermal injury. Use of the MTIRP as an educational tool for carers would promote increased understanding and, thus, more appropriate support.

Burns

A high angle neutron fibre diffraction study of the hydration of the A conformation of the DNA double helix.

A high angle neutron fibre diffraction study of the distribution of water around the A-form of DNA has been performed using the diffractometer D19 at the Institut Laue-Langevin, Grenoble. These experiments have exploited the ability to replace H2O surrounding the DNA by D2O so that isotopic difference Fourier maps can be computed in which peaks are identified with the distribution of water in the unit cell. All peaks of significant height have been accounted for by four families of water molecules whose positions and occupancies have been determined using least squares refinement. The coordinates of the water peaks making up each family do not deviate significantly from a regular helical arrangement with the same parameters as the DNA. Two of these families are of particular interest. The first consists of water molecules in the major groove linking successive charged phosphate oxygens along the polynucleotide chains. The second is associated with bases in the major groove and forms a central core of density along the helix axis. These two families provide a layer of hydration lining the interior wall of the major groove leaving a central channel to accommodate cations. The relationship between these observations and conformational stability is discussed.

DNA

The application of sensory change to reduce stereotyped behavior.

A combined reversal and multiple baseline design was utilized to assess reduction of repetitive hand movements for three severely mentally retarded children. Stereotypy was assessed during baseline (reinforcement for on task behavior) and sensory change (rings and reinforcement, rings, and faded rings) conditions. The results indicated sensory change effectively reduced the target responses. These results were durable up to 4 hours. We conclude that the procedure used in this study is a non-intrusive intervention that is an extension of the current literature pertaining to sensory extinction.

Adolescent

Artifactual effects of sensory-integrative therapy on self-injurious behavior.

Three individuals who exhibited self-injurious behavior (SIB) were exposed to sensory-integrative therapy. Prior to treatment, a functional analysis baseline was conducted to identify the motivational features of their SIB. One subject's SIB appeared to be an attention-getting response (maintained by positive reinforcement), which varied subsequently as a function of attention being either withheld or provided noncontingently during sensory-integration sessions. The 2nd subject displayed a pattern of responding suggestive of stereotypic SIB (maintained by automatic reinforcement), which paradoxically increased during sensory-integration sessions. The 3rd subject's SIB appeared to function as an escape response (maintained by negative reinforcement), and his behavior during sensory-integration sessions was similar to that observed during baseline sessions in which demands were not present. The SIB of all 3 subjects later was reduced when behavior interventions were applied. The data presented raise questions about the active components of sensory-integrative therapy and the functional types of SIB for which it might be appropriate.

Adolescent

Neutron fibre diffraction study of DNA hydration.

Interactions with water are crucial to the conformation assumed by the DNA double helix. The location of water around the D conformation has been investigated in a neutron fibre diffraction study which shows that water is ordered in the minor groove of the DNA. The D conformation is important since its occurrence is limited to specific DNA base pair sequences which have been identified as functionally significant. This study is of particular interest because the D conformation has not been reported in single crystal studies of oligonucleotides.

DNA

A practical strategy for ongoing reinforcer assessment.

There is a need for practical methods of reinforcer assessment that systematically track ongoing changes in clients' preferences. In this study, the effects of a time-efficient reinforcer assessment package were evaluated in a multiple baseline across 3 preschoolers with autism, comparing individualized item selections by experienced teachers with children's presession preferences for items of various sensory qualities. Systematic assessment of children's reinforcers for correct responding virtually eliminated nontargeted maladaptive behaviors, as well as yielding expected improvements in accuracy. The powerful side-effects of potent reinforcers underline the importance of increased attention to reinforcer assessment in research and practice.

Autistic Disorder

Study of ethanol-lysozyme interactions using neutron diffraction.

Single-crystal neutron diffraction has been used to observe the interactions between deuterated ethanol (CD3CD2OH) and lysozyme in triclinic crystals of hen egg white lysozyme soaked in 25% (v/v) ethanol solutions. A total of 6047 observed reflections to a resolution of 2 A were used, and 13 possible ethanol sites were identified. The three highest occupied sites are close to locations for bromoethanol found in an earlier study by Yonath et al. [Yonath, A., Podjarny, A., Honig, B., Traub, W., Sielecki, A., Herzberg, O., & Moult, J. (1978) Biophys. Struct. Mech. 4, 27-36]. Structure refinements including a model for the flat solvent lead to a final crystallographic agreement factor of 0.097. Comparison with earlier neutron studies on triclinic lysozyme showed that neither the molecular structure nor the thermal motions were affected significantly by the ethanol. A detailed analysis of the ethanol-lysozyme contacts showed 61% of these to be with hydrophobic sites, in agreement with the dominant hydrophobic nature of ethanol. This, together with the fact that the molecular structure of lysozyme is not perturbed, suggests a model for denaturation of lysozyme by alcohol, which proceeds via a dehydration of the protein at high alcohol concentration.

Animals

Exchange of individual hydrogens for a protein in a crystal and in solution.

A preliminary comparison of the solvent exchange of individual hydrogens of a protein in solution and in a crystal has been possible by using data for lysozyme from 1H nuclear magnetic resonance and neutron diffraction studies. It is suggested that this approach enables a direct comparison of local dynamical behaviour in the two states. The results indicate markedly similar behaviour for many residues, but significant differences are indicated in several regions of the protein.

Animals

Sedation for outpatient conservative dentistry. A trial of pentazocine supplementation to diazepam and local analgesia techniques.

Pentazocine 30 mg. or 15 mg or a placebo, was administered randomly to forty-nine patients undergoing conservative dental treatment in combination with a local analgesic block and intravenous diazepam. Simple cardiorespiratory measurements were made throughout the treatment period. Patients in the 30 mg pentazocine group required some 6 mg diazepam less than the placebo (control) group (P less than 0.05). Patients receiving 15 mg pentazocine also required less diazepam compared to the control group, but this difference was not statistically significant. There were no significant differences between the three groups either in recovery times or the cardiorespiratory measurements.

Adolescent