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Biomedical subjects

M Samuels

Publications and source records attributed to M Samuels.

At least 19 recordsLinked to original sources

Resuscitating paediatric induction: an action research approach.

OBJECTIVES: To establish teaching objectives, methods and assessment for a paediatric induction programme. DESIGN: Action research over a 2-year period. PARTICIPANTS: 88 doctors from three hospitals. MAIN OUTCOME MEASURES: These were end-of-course evaluations, using Likert scales, and free comments; independent evaluation by the West Midlands Deanery 4 months after courses, in which participating and non-participating units were compared, and summative assessment of trainees involving multiple-choice questions, a basic life-support scenario and an illness scenario. RESULTS: 88 participants attended four 3-day courses over 2 years. Mean satisfaction ratings were very high for content, personal value, and presentation. There was a significant rise in Deanery evaluation scores, compared with non-significant change in other hospitals, and there were excellent pass rates for trainees. CONCLUSIONS: Trainees strongly approve of induction with clear objectives, active teaching, and validated assessment.

Curriculum↗

Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23.

Coronary heart disease (CHD) accounts for half of the 1 million deaths annually ascribed to cardiovascular disease and for almost all of the 1.5 million acute myocardial infarctions. Within families affected by early and apparently heritable CHD, dyslipidemias have a much higher prevalence than in the general population; 20%-30% of early familial CHD has been ascribed to primary hypoalphalipoproteinemia (low HDL-C). This study assesses the evidence for linkage of low HDL-C to chromosomal region 11q23 in 105 large Utah pedigrees ascertained with closely related clusters of early CHD and expanded on the basis of dyslipidemia. Linkage analysis was performed by use of 22 STRP markers in a 55-cM region of chromosome 11. Two-point analysis based on a general, dominant-phenotype model yielded LODs of 2.9 for full pedigrees and 3.5 for 167 four-generation split pedigrees. To define a localization region, model optimization was performed using the heterogeneity, multipoint LOD score (mpHLOD). This linkage defines a region on 11q23.3 that is approximately 10 cM distal to-and apparently distinct from-the ApoAI/CIII/AIV gene cluster and thus represents a putative novel localization for the low HDL-C phenotype.

Cholesterol, HDL↗

Maternal behaviors associated with smothering: a preliminary descriptive study.

OBJECTIVES: To describe maternal behavior in 15 women identified as having smothered their children. DESIGN: A descriptive study of maternal behavior and interaction with her child, using videotapes of mother and child together. These were obtained by covert video surveillance in a hospital setting. Maternal behavior was rated using an assessment schedule designed to be used with video. RESULTS: The mothers showed a range of behaviors. Three groups emerged; one whose interaction with the child resembled normal maternal behavior, a second who interacted in a hostile way, and a third who showed a paucity of interaction. CONCLUSION: These preliminary data suggest that smothering may reflect more than one type of abnormal maternal relationship or attitude towards children. This may have implications for treatment and prognosis.

Adult↗

The experiences and views of parents who care for ventilator-dependent children.

Discussion in this paper is drawn from the literature examining the management of children with long-term assisted ventilation, and a study of parents' experiences and views of caring for their ventilator-dependent child at home. Difficulties in undertaking research into this group of children are highlighted. Recommendations are proposed regarding future multidisciplinary, multiagency service development in order to meet the needs of ventilator-dependent children and their families.

Adaptation, Psychological↗

Activities of the Sex-lethal protein in RNA binding and protein:protein interactions.

The Drosophila sex determination gene Sex-lethal (Sxl) controls its own expression, and the expression of downstream target genes such as transformer , by regulating pre-mRNA splicing and mRNA translation. Sxl codes an RNA-binding protein that consists of an N-terminus of approximately 100 amino acids, two 90 amino acid RRM domains, R1 and R2, and an 80 amino acid C-terminus. In the studies reported here we have examined the functional properties of the different Sxl protein domains in RNA binding and in protein:protein interactions. The two RRM domains are responsible for RNA binding. Specificity in the recognition of target RNAs requires both RRM domains, and proteins which consist of the single domains or duplicated domains have anomalous RNA recognition properties. Moreover, the length of the linker between domains can affect RNA recognition properties. Our results indicate that the two RRM domains mediate Sxl:Sxl protein interactions, and that these interactions probably occur both in cis and trans. We speculate that cis interactions between R1 and R2 play a role in RNA recognition by the Sxl protein, while trans interactions stabilize complex formation on target RNAs that contain two or more closely spaced binding sites. Finally, we show that the interaction of Sxl with the snRNP protein Snf is mediated by the R1 RRM domain.

Amino Acid Sequence↗

Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1.

The fission yeast Sty1 stress-activated MAP kinase is crucial for the cellular response to a variety of stress conditions. Accordingly, sty1- cells are defective in their response to nutrient limitation, lose viability in stationary phase, and are hypersensitive to osmotic stress, oxidative stress, and UV treatment. Some of these phenotypes are caused by Sty1-dependent regulation of the Atf1 transcription factor, which controls both meiosis-specific and osmotic stress-responsive genes. However, in this report we demonstrate that the cellular response to oxidative stress and to treatment with a variety of cytotoxic agents is the result of Sty1 regulation of the Pap1 transcription factor, a bZip protein with structural and DNA binding similarities to the mammalian c-Jun protein. We show that both Sty1 and Pap1 are required for the expression of a number of genes involved in the oxidative stress response and for the expression of two genes, hba2+/bfr1+ and pmd1+, which encode energy-dependent transport proteins involved in multidrug resistance. Furthermore, we demonstrate that Pap1 is regulated by stress-dependent changes in subcellular localization. On imposition of oxidative stress, the Pap1 protein relocalizes from the cytoplasm to the nucleus in a process that is dependent on the Sty1 kinase. This relocalization is the result of regulated protein export, rather than import, and involves the Crm1 (exportin) nuclear export factor and the dcd1+/pim1+ gene that encodes an Ran nucleotide exchange factor.

Activating Transcription Factor 1↗

The Atf1 transcription factor is a target for the Sty1 stress-activated MAP kinase pathway in fission yeast.

The atf1+ gene of Schizosaccharomyces pombe encodes a bZIP transcription factor with strong homology to the mammalian factor ATF-2. ATF-2 is regulated through phosphorylation in mammalian cells by the stress-activated mitogen-activated protein (MAP) kinases SAPK/JNK and p38. We show here that the fission yeast Atf1 factor is also regulated by a stress-activated kinase, Sty1. The Sty1 kinase is stimulated by a variety of different stress conditions including osmotic and oxidative stress and heat shock. Deletion of the atf1+ gene results in many, but not all, of the phenotypes associated with loss of Sty1, including sensitivity to environmental stress and inability to undergo sexual conjugation. Furthermore, we identify a number of target genes that are induced rapidly in a manner dependent upon both the Sty1 kinase and the Atf1 transcription factor. These genes include gpd1+, which is important for the response of cells to osmotic stress, the catalase gene lambda important for cells to combat oxidative stress, and pyp2+, which encodes a tyrosine-specific MAP kinase phosphatase. Induction of Pyp2 by Atf1 is direct in that it does not require de novo protein synthesis and results in a negative feedback loop that serves to control signaling through the Sty1/Wis1 pathway. We show that Atf1 associates stably and is phosphorylated by the Sty1 kinase in vitro. Taken together, these results indicate that the interaction between AM and Sty1 is direct. These findings highlight a remarkable level of conservation in transcriptional control by stress-activated MAP kinase pathways between fission yeast and mammalian cells.

Activating Transcription Factor 1↗

A hypothesis-assessment model of categorical argument strength.

According to the proposed hypothesis-assessment model, the strength of inductive categorical arguments, such as {All Robins Have Substance X therefore All Birds Have Substance X}, is determined by the same factors that affect hypothesis plausibility in the everyday social milieu. The premises of such arguments are viewed as evidence and the conclusion is viewed as a hypothesis. Specifically, the proposed model predicts that the perceived strength of general-conclusion categorical arguments will be a function of (a) the number of premises that instantiate the conclusion; (b) the scope of the conclusion; and (c) the number of accessed alternatives to the conclusion. In Experiment 1, one group rated the strength of individual arguments and another constructed superordinate hypotheses in response to the premise information alone. Most of the variance in perceived argument strength was accounted for by the proposed predictors, R = .94. Experiment 2 employed a new set of arguments and included an additional forced-choice condition in which subjects had to choose the stronger of two arguments. Again, the correlation between predictors and argument strength was high, R = .91, and, all significant forced-choice preferences except one were correctly predicted by the model. The one unpredicted preference suggests the need to include conclusion accessibility as a fourth factor. Also, on a subset of the forced-choice pairs in which no significant preference was observed, two distinct patterns of responding were detected-one predicted and the other unanticipated. Some strengths and limitations of the proposed hypothesis-assessment model are discussed in light of these results.

Adult↗

Home monitoring of infants at increased risk of sudden death.

Home apnoea and cardiorespiratory monitors are commonly used in the UK, the rest of Europe and USA in infants at increased risk of 'sudden infant death'. The efficacy of apnoea and cardiorespiratory monitors remains unknown. The use of transcutaneous oxygen monitoring is presented as an alternative method of home monitoring. Recommendations are proposed regarding nursing practice and the future of home monitoring in infants at increased risk of sudden death.

Attitude to Health↗

Sex-specific control of Sex-lethal is a conserved mechanism for sex determination in the genus Drosophila.

In D. melanogaster the binary switch gene Sex-lethal (Sxl) plays a pivotal role in somatic sex determination -- when the Sxl gene is on the female pathway is followed, while the male pathway is followed when the gene is off. In the present study we have asked whether the Sxl gene is present in other species of the genus Drosophila and whether it is subject to a similar sex-specific on-off regulation. Sxl proteins were found in all of the drosophilids examined, and they display a sex-specific pattern of expression. Furthermore, characterization of the Sxl gene in the distant drosophilan relative, D. virilis, reveals that the structure and sequence organization of the gene has been well conserved and that, like melanogaster, alternative RNA processing is responsible for its sex-specific expression. Hence, this posttranscriptional on-off regulatory mechanism probably existed before the separation of the drosophilan and sophophoran subgenera and it seems likely that Sxl functions as a sex determination switch gene in most species in the Drosophila genus. Although alternative splicing appears to be responsible for the on-off regulation of the Sxl gene in D. virilis, this species is unusual in that Sxl proteins are present not only in females but also in males. The D. virilis female and male proteins appear to be identical over most of the length except for the amino-terminal approx. 25 aa which are encoded by the differentially spliced exons. In transcriptionally active polytene chromosomes, the male and female proteins bind to the same cytogenetic loci, including the sites corresponding to the D. virilis Sxl and tra genes. Hence, though the male proteins are able to interact with appropriate target pre-mRNAs, they are apparently incapable of altering the splicing pattern of these pre-mRNAs.

Alternative Splicing↗

Future trends in the health care economy.

Most articles on the future of health care are by professionals involved in the delivery of health care services. This article is unique in that trends are examined from the perspective of the public and purchasers of care. The authors focus on 12 trends that are or will be affecting the industry, and on the sometimes unintended consequences and new conflicts that may develop.

Capital Financing↗

Negative extrathoracic pressure ventilation--evaluation of the neck seal.

The effect of the neck seal used in the application of negative extra-thoracic pressure ventilation was studied using near infrared spectroscopy. Changes in cerebral blood volume (CBV) were monitored during discontinuation of negative pressure and during removal of the neck seal. CBV increased by 0.17 ml 100 ml brain-1 (95% CI +0.0875 to +0.481) when negative pressure was discontinued. Removal of the neck seal had no significant effect on CBV. It is concluded that the neck seal does not cause significant jugular venous occlusion.

Blood Volume Determination↗