Biomedical subjects

G W Martin

Publications and source records attributed to G W Martin.

At least 19 recordsLinked to original sources

PubMed2001

Interplay between termination and translation machinery in eukaryotic selenoprotein synthesis.

Termination of translation in eukaryotes is catalyzed by eRF1, the stop codon recognition factor, and eRF3, an eRF1 and ribosome-dependent GTPase. In selenoprotein mRNAs, UGA codons, which typically specify termination, serve an alternate function as sense codons. Selenocysteine incorporation involves a unique tRNA with an anticodon complementary to UGA, a unique elongation factor specific for this tRNA, and cis-acting secondary structures in selenoprotein mRNAs, termed SECIS elements. To gain insight into the interplay between the selenocysteine insertion and termination machinery, we investigated the effects of overexpressing eRF1 and eRF3, and of altering UGA codon context, on the efficiency of selenoprotein synthesis in a transient transfection system. Overexpression of eRF1 does not increase termination at naturally occurring selenocysteine codons. Surprisingly, selenocysteine incorporation is enhanced. Overexpression of eRF3 did not affect incorporation efficiency. Coexpression of both factors reproduced the effects with eRF1 alone. Finally, we show that the nucleotide context immediately upstream and downstream of the UGA codon significantly affects termination to incorporation ratios and the response to eRF overexpression. Implications for the mechanisms of selenocysteine incorporation and termination are discussed.

Base Sequence↗

PubMed2001

Selenocysteine incorporation directed from the 3'UTR: characterization of eukaryotic EFsec and mechanistic implications.

The mechanism of selenocysteine incorporation in eukaryotes has been assumed for almost a decade to be inherently different from that in prokaryotes, due to differences in the architecture of selenoprotein mRNAs in the two kingdoms. After extensive efforts in a number of laboratories spanning the same time frame, some of the essential differences between these mechanisms are finally being revealed, through identification of the factors catalyzing cotranslational selenocysteine insertion in eukaryotes. A single factor in prokaryotes recognizes both the selenoprotein mRNA, via sequences in the coding region, and the unique selenocysteyl-tRNA, via both its secondary structure and amino acid. The corresponding functions in eukaryotes are conferred by two distinct but interacting factors, one recognizing the mRNA, via structures in the 3' untranslated region, and the second recognizing the tRNA. Now, with these factors in hand, crucial questions about the mechanistic details and efficiency of this intriguing process can begin to be addressed.

3' Untranslated Regions↗

PubMed2001

Person-centred care for people with dementia: a quality audit approach.

This paper addresses the concept of person-centred care for people with dementia by consideration of an audit process using dementia care mapping as the audit tool. It is argued that this tool is best for identifying the lived experiences of the people in receipt of care. As a result it is able to identify the overall culture of care and its level of 'person-centred' approach. The audit was conducted on 12 units, half of which were day units and the others catering for inpatients. Five patients were mapped on each day for a 4-day period. The results give some idea of the quality of care and identify where improvement is necessary. Scores such as well-being values and the Dementia Care Index give clear signposts to the level of person-centred care and highlight where staff development is necessary. Recommendations are given to aid on-going planning.

Dementia↗

PubMed2001

Selenocysteine codons decrease polysome association on endogenous selenoprotein mRNAs.

BACKGROUND: Selenocysteine incorporation has been reported to be inefficient in all systems studied, including Escherichia coli, baculovirus-insect cell systems, rabbit reticulocyte in vitro translation systems, transiently transfected mammalian cells, and intact animals. Nonetheless, full-length selenoproteins containing up to 17 selenocysteine residues are produced in animals, indicating that the efficiency observed in manipulated systems might not accurately reflect the true efficiency of this process in nature. RESULTS: To begin to address this apparent discrepancy, we have examined the polysome profiles of endogenously expressed selenoprotein mRNAs in a mammalian cell line, and compared them with nonselenoprotein mRNAs. We report that three selenoprotein mRNAs, type 1 deiodinase, glutathione peroxidase and selenoprotein P, are under-loaded with ribosomes, based on their predicted open reading frame sizes. The average numbers of ribosomes per mRNA correspond to the sizes predicted by termination at the UGA selenocysteine codons. Appropriate loading on the type 1 deiodinase mRNA is seen following substitution of a cysteine codon for the selenocysteine codon, indicating that the UGA codon confers a translational penalty on the mRNA. Surprisingly, ribosomal loading is also increased by the expression of eukaryotic release factors eRF1 and eRF3. CONCLUSIONS: These results suggest that the presence of a selenocysteine codon confers a translational penalty on selenoprotein mRNAs, and that increased levels of release factors may alter the kinetics of termination.

Animals↗

PubMed2000

Dementia care mapping: an approach to quality audit of services for people with dementia in two health districts.

The audit reported in this paper and submitted to the Psychiatry of Old Age Management group, assessed six units within each of two health districts in the UK. Using a nonparticipatory observation method in the units selected, the aim was to measure quality and the environment of care. Dependency levels of the clients/residents were also estimated to give a clearer picture of the setting and the care requirements. This was intended to establish a baseline for the units mapped and to enable care developments to be focussed upon intended outcomes. Results led to a number of observations related to the levels of interaction between staff and clients/residents, the need for a wider range of activities to promote person-centred care, and a suggested route to the improvement in quality of life for this vulnerable group of people. Assessment of dependency levels linked to the results of the mapping showed that high dependency does not lead automatically to a lower quality of person centred care.

Activities of Daily Living↗

PubMed2000

Anti oppressive practice: a route to the empowerment of people with dementia through communication and choice.

This short study looks at the issue of anti oppressive practice and the way that it relates to the care of people with dementia. In particular it considers ways in which people can be empowered and given choices around aspects of day-to-day living in a care setting. The study took place over a period of 6 months and utilized the Dementia Care Mapping (DCM) observation process to assess the level of well being of residents in the setting studied. The results can only be seen as a first stage in the process of understanding ways in which people with dementia may be empowered. It is demonstrated that a change of practice developed over the 6 months between the two observation periods. Areas such as communications and day-to-day activities are examined to identify both problems and strategies for such change. The conclusion highlights the need to continue the mapping exercise as a way of ensuring that change is not only maintained but also advanced.

Activities of Daily Living↗

PubMed1999

Two distinct SECIS structures capable of directing selenocysteine incorporation in eukaryotes.

Translation of UGA as selenocysteine requires specific RNA secondary structures in the mRNAs of selenoproteins. These elements differ in sequence, structure, and location in the mRNA, that is, coding versus 3' untranslated region, in prokaryotes, eukaryotes, and archaea. Analyses of eukaryotic selenocysteine insertion sequence (SECIS) elements via computer folding programs, mutagenesis studies, and chemical and enzymatic probing has led to the derivation of a predicted consensus structural model for these elements. This model consists of a stem-loop or hairpin, with conserved nucleotides in the loop and in a non-Watson-Crick motif at the base of the stem. However, the sequences of a number of SECIS elements predict that they would diverge from the consensus structure in the loop region. Using site-directed mutagenesis to introduce mutations predicted to either disrupt or restore structure, or to manipulate loop size or stem length, we show that eukaryotic SECIS elements fall into two distinct classes, termed forms 1 and 2. Form 2 elements have additional secondary structures not present in form 1 elements. By either insertion or deletion of the sequences and structures distinguishing the two classes of elements while maintaining appropriate loop size, conversion of a form 1 element to a functional form 2-like element and of a form 2 to a functional form 1-like element was achieved. These results suggest commonality of function of the two classes. The information obtained regarding the existence of two classes of SECIS elements and the tolerances for manipulations of stem length and loop size should facilitate designing RNA molecules for obtaining high-resolution structural information about these elements.

Animals↗

PubMed1998

The test-retest reliability of the frequency of multiple drug use in young drug users entering treatment.

Assessment of multiple drug use relies primarily on self-report. Several studies support the reliability of client self-reports of drug use but these studies have not involved assessment of the actual frequency of drug use. This test-retest reliability study assessed the frequency of drug use in a clinical sample of 103 multiple drug users, aged 16-25 years. At initial assessment, all participants completed the Drug Use History Form (DUHF) that inquired about the number of drug-using days and the daily frequency of use for 13 drug classes during four time intervals. The DUHF was readministered 2-4 weeks later. Reliability was assessed using Intra-class correlations (ICC's). The results indicated that clients do, in general, reliably report both the number of days of use and daily frequencies. The two frequency measures were not highly correlated. Reliability estimates declined over time but most markedly after 90 days, suggesting that assessments of drug use can be reliably extended beyond 30 days. Frequency estimates based solely on the number of days of use of a substance may be unreliable estimates of actual drug consumption, indicating limitations to this commonly used outcome measure.

Adolescent↗

PubMed1998

A social marketing model for disseminating research-based treatments to addictions treatment providers.

AIMS: Researchers must develop effective strategies for disseminating research-based treatments. This study evaluates the application of a dissemination model based on principles of social marketing and diffusion theory. DESIGN: A case study describes how the model was implemented. A qualitative design was employed to examine rates of adoption and adaptation of an early intervention program by a targeted system of addictions agencies. SETTING: The interventions were developed at the Addiction Research Foundation in Toronto and disseminated to Assessment and Referral (A/R) Centres in Ontario, Canada. PARTICIPANTS: Study participants included the managers and a designated therapist for 33 participating A/R centres. MEASUREMENTS: Managers were asked mainly open-ended questions concerning whether their agency had made a formal decision to adopt the intervention and whether therapists in their agency were using the early intervention program. "Adoption" was operationalized as offering the complete four-session intervention to at least one client. FINDINGS: At 12 months after the completion of training workshops, 68% of 34 agencies in the target system had adopted the program while 85% of the agencies were using some components of the intervention with clients. CONCLUSIONS: The dissemination model appeared to be effective although its application proved to be time-consuming and labour-intensive. The "market analysis", systems focus and field-test components of the model appeared to contribute to its success.

Delivery of Health Care↗

PubMed1998

Ritual action and its effect on the role of the nurse as advocate.

Problems related to the ability of the nurse to act as advocate for patients have caused dilemmas in the profession over recent years. This paper seeks to address the issue from the aspect of ritual action which pervades the day-to-day activities of nurses and could therefore have an effect on nurse-patient relations. By looking at a short study based on data from nurses working with dying patients, part of work in progress on the subject, it is possible to draw some conclusions about the effect that such rituals and routines have on practice. Examination of the work of Douglas leads to speculation about the ways that rituals associated with restricted language can undermine the nurse's ability to advocate successfully. Results from the study are limited given the small sample, but they give some indication of trends and possibilities that more exhaustive research may confirm.

Communication Barriers↗

PubMed1998

Empowerment of dying patients: the strategies and barriers to patient autonomy.

The growing debate about the ability of the nurse to empower patients has featured frequently in the nursing journals over recent years. This paper seeks to address the issue around the need to empower dying patients by an examination of nurses' written reflections on critical incidents in their practice. Geertz's 'thick description' has been used to interpret the data. The issues of power and professionalism are central to the discussion. The results are tentative given the sample size but point towards a redefinition of the empathetic approach and the adoption of a 'facilitative' approach to the sharing of power. The paper recommends careful examination of the role of the nurse and the communication process to identify further barriers to patient empowerment.

Communication Barriers↗

PubMed1998

Communication breakdown or ideal speech situation: the problem of nurse advocacy.

The issue of advocacy has dominated discussion of the ethical dilemmas facing nurses. However, despite this, nurses seem to be no further towards a solution of how they can be effective advocates for patients without compromising their working identity or facing conflicts of loyalty. This article considers some of the problems around advocacy and, by the use of critical incidents written by nurses involved in a diploma module, attempts to highlight where the problem could lie. A communications model is outlined, using a theoretical framework taken from the work of Jürgen Habermas, and applied to nursing practice. Finally, two examples are given from the research, which illustrate how the model could be used, highlighting the problems and pitfalls that still have to be overcome. The conclusion is a positive one, in that it suggests that advocacy is possible if nurses re-examine their practice in the light of the model proposed.

Communication↗

PubMed1998

Rethinking the role of residential treatment for individuals with substance abuse problems.

The Substance Abuse Bureau of the Ontario Ministry of Health recently launched the Ontario Addictions Treatment Services Rationalization Project to increase the capacity of existing services and restructure the service delivery system. One of the recommended strategies was to shorten the length of stay of residential treatment from four to three weeks. Concerns have been expressed by some service providers that this policy change is not consistent with available empirical evidence. This paper reviews relevant research evidence and suggests a new role for residential treatment of substance abusers.

Alcoholism↗

PubMed1998

Functionality of mutations at conserved nucleotides in eukaryotic SECIS elements is determined by the identity of a single nonconserved nucleotide.

In eukaryotes, the specific cotranslational insertion of selenocysteine at UGA codons requires the presence of a secondary structural motif in the 3' untranslated region of the selenoprotein mRNA. This selenocysteine insertion sequence (SECIS) element is predicted to form a hairpin and contains three regions of sequence invariance that are thought to interact with a specific protein or proteins. Specificity of RNA-binding protein recognition of cognate RNAs is usually characterized by the ability of the protein to recognize and distinguish between a consensus binding site and sequences containing mutations to highly conserved positions in the consensus sequence. Using a functional assay for the ability of wild-type and mutant SECIS elements to direct cotranslational selenocysteine incorporation, we have investigated the relative contributions of individual invariant nucleotides to SECIS element function. We report the novel finding that, for this consensus RNA motif, mutations at the invariant nucleotides are tolerated to different degrees in different elements, depending on the identity of a single nonconserved nucleotide. Further, we demonstrate that the sequences adjacent to the minimal element, although not required for function, can affect function through their propensity to base pair. These findings shed light on the specific structure these conserved sequences may form within the element. This information is crucial to the design of strategies for the identification of SECIS-binding proteins, and hence the elucidation of the mechanism of selenocysteine incorporation in eukaryotes.

Base Sequence↗

PubMed1997

RNA and protein requirements for eukaryotic selenoprotein synthesis.

Selenium has been recognized as an essential nutrient in animals since the 1950s. Demonstration of the role of dietary selenium in protection from oxidative stress followed in the early 1970s, and was largely attributed to its presence as an integral part of cellular glutathione peroxidase. However, the functions of this enzyme did not explain many of the other effects of selenium deficiency. The identification of other mammalian selenoproteins during the last few years has provided new insights into the functions of this trace nutrient. The discovery that type 1 deiodinase (D1) is a selenoenzyme, in addition to unveiling an essential role for selenium in thyroid hormone action, has had more far-reaching implications. Studies of this protein opened the door for investigation of the requirements for eukaryotic selenoprotein synthesis, and the features that distinguish this pathway from the corresponding prokaryotic pathway. Selenium is present in a number of prokaryotic and eukaryotic proteins in the form of the unusual amino acid, selenocysteine. Incorporation of selenocysteine into these proteins requires a novel translation step in which UGA specifies selenocysteine insertion. Since UGA codons are typically recognized as translation stop signals, an intriguing question is raised: How does a cell recognize and distinguish a UGA selenocysteine codon from a UGA stop codon? In this review, we will focus on what is known about selenocysteine incorporation in eukaryotes, briefly summarizing initial studies and discussing a few recent advances in our understanding of this unique "recoding" process.

Animals↗

PubMed1996

An approach to the facilitation and assessment of critical thinking in nurse education.

Problems around the production of written work to a given level, i.e. critical analysis, have dominated discussion of course standards in recent months since the introduction of the higher award pathway in post-registered nurse education. This paper seeks to address these concerns by suggesting a model for teachers to use in course planning and by use of an action research approach indicates to what extent: 1. The model works with two specific courses. 2. It is possible to assess student performance by an examination of their written work. The paper attempts to address issues related to why nurses have difficulty with the concepts and to what extent issues of power and culture play a part in such difficulty. The action research itself is based around two cycles of the research model using examples of student work to explain results. Overall the results are mixed but show that the adoption of a problem solving approach to lesson planning together with tutorials sustained throughout the course can bring about the required level in students final written work.

Clinical Competence↗

PubMed1996

Selenocysteine incorporation in eukaryotes: insights into mechanism and efficiency from sequence, structure, and spacing proximity studies of the type 1 deiodinase SECIS element.

SECIS elements are stem-loop structures located in the 3' untranslated regions (UTRs) of eukaryotic selenoprotein mRNAs that are required for directing cotranslational selenocysteine incorporation at UGA codons. In prokaryotes, stem-loops mediating selenocysteine incorporation are located immediately downstream of the UGA selenocysteine codon, in the coding region. Previous characterization studies of the mammalian SECIS elements of type 1 deiodinase, glutathione peroxidase, and selenoprotein P showed that conserved nucleotides in the loops and unpaired bulges, and base pairing in the stems are required for SECIS function. These initial studies utilized approximately 175-230-nt segments of the 3'UTRs of the selenoprotein mRNAs. Here we define the minimal functional rat type 1 deiodinase SECIS element, a 45-nt segment, the 5' boundary of which corresponds precisely to the 5'-most critical conserved nucleotide identified previously. We also define base pairing requirements in the stem of this element. In view of the presence of SECIS elements in the open reading frames (ORFs) of bacterial selenoproteins, we examine the effects in the type 1 deiodinase of extending the ORF into the SECIS element, and find that this dramatically inhibits SECIS function. Finally, we define a minimal spacing requirement of 51-111 nt between a eukaryotic UGA selenocysteine codon and SECIS element.

Animals↗

PubMed1995

The Drug Avoidance Self-Efficacy Scale.

Several scales have been developed to measure self-efficacy for addictive behaviors but there is no such scale applicable to multiple drug users. The Drug Avoidance Self-Efficacy Scale (DASES) was developed to fill this gap. The properties of the scale were evaluated using a sample of 373 young multiple-drug users 16 to 30 years old presenting for treatment at the Addiction Research Foundation. The 16-item scale appeared to be unidimensional. Cronbach's alpha was .9140. Construct validity, evaluated on a subset of the sample, was evident in significant correlations with concurrent measures of drug use severity and differential rates of changes in self-efficacy associated with two types of treatment. The DASES appears to be a reliable and valid scale for the measurement of self-efficacy in multiple-drug users.

Adolescent↗