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Biomedical subjects

S Forrest

Publications and source records attributed to S Forrest.

At least 19 recordsLinked to original sources
PubMed2000

Mental health service user involvement in nurse education: exploring the issues.

This paper reports on findings and issues arising from a study designed to promote mental health service users' involvement in a preregistration nursing curriculum. Users' views about the knowledge, skills and attributes required by mental health nurses were explored to inform the curriculum design. Strategies that would facilitate long term, active user involvement in the design and delivery of the curriculum were also explored. Findings are presented with concurrent discussion of issues arising from the research process in relation to user involvement in education. The issue of 'conflict' explores findings relating to users' views of a 'good' mental health nurse and inherent conflicts between user and professional views are highlighted. The representativeness of the research participants is explored and debated in relation to service user involvement in nurse education. Finally, the concepts of 'involvement' and 'tokenism' are discussed and recommendations made about how active user involvement in nurse education can be achieved.

Curriculum↗
PubMed1999

Variable efficacy of repeated annual influenza vaccination.

Conclusions have differed in studies that have compared vaccine efficacy in groups receiving influenza vaccine for the first time to efficacy in groups vaccinated more than once. For example, the Hoskins study [Hoskins, T. W., Davis, J. R., Smith, A. J., Miller, C. L. & Allchin, A. (1979) Lancet i, 33-35] concluded that repeat vaccination was not protective in the long term, whereas the Keitel study [Keitel, W. A., Cate, T. R., Couch, R. B., Huggins, L. L. & Hess, K. R. (1997) Vaccine 15, 1114-1122] concluded that repeat vaccination provided continual protection. We propose an explanation, the antigenic distance hypothesis, and test it by analyzing seven influenza outbreaks that occurred during the Hoskins and Keitel studies. The hypothesis is that variation in repeat vaccine efficacy is due to differences in antigenic distances among vaccine strains and between the vaccine strains and the epidemic strain in each outbreak. To test the hypothesis, antigenic distances were calculated from historical hemagglutination inhibition assay tables, and a computer model of the immune response was used to predict the vaccine efficacy of individuals given different vaccinations. The model accurately predicted the observed vaccine efficacies in repeat vaccinees relative to the efficacy in first-time vaccinees (correlation 0.87). Thus, the antigenic distance hypothesis offers a parsimonious explanation of the differences between and within the Hoskins and Keitel studies. These results have implications for the selection of influenza vaccine strains, and also for vaccination strategies for other antigenically variable pathogens that might require repeated vaccination.

Antigens, Viral↗
PubMed1999

Kallmann syndrome gene (KAL-X) is not mutated in schizophrenia.

Kallmann syndrome and schizophrenia share several clinical features, including dysfunctional olfactory ability, hypogonadotrophic hypogonadism, an excess of affected males, and psychiatric presentation. Because of this congruence, it has been proposed that up to 70% of male schizophrenics might have mutations affecting the function or expression of the gene mutated in Kallmann syndrome, KAL-X. We identified and studied 9 unrelated males with schizophrenia (as defined by DSM-IIIR criteria) who also have severe anosmia (first percentile of normal range) and low sex drive (seventh percentile of the normal range), and we sequenced the exons and the intron-exon junctions of the KAL-X gene for each. We found no mutations, and conclude that schizophrenia is rarely, if ever, due to a mutation in the coding sequence or splice junctions of KAL-X.

Extracellular Matrix Proteins↗
PubMed1999

Phenotypic variability of Filipino beta(o)-thalassemia/HbE patients in Indonesia.

Three Indonesian patients with identical genotypes, each compound heterozygotes for Filipino beta(o)-thalassemia/HbE, expressed different clinical severities. One patient has mild disease and is transfusion independent, while the other two are severely affected and transfusion dependent. The size of the Filipino beta(o)-globin gene deletion was confirmed to be 45 kb, resolving conflicting values given in the literature. Neither ameliorating genetic factors such as alpha-globin gene deletions or the XmnI restriction site polymorphism at position -158 upstream of the (G)gamma-globin gene, nor differences in beta-globin gene haplotype, explain the phenotypic variation. These observations have implications for the development of antenatal diagnosis in Indonesia, as at present it is not possible to give an accurate prediction of severity of phenotype for this common genotype.

Child↗
PubMed1999

Reliable and sensitive detection of premature termination mutations using a protein truncation test designed to overcome problems of nonsense-mediated mRNA instability.

The protein truncation test (PTT) is a mutation-detection method used to scan for premature termination (nonsense) mutations. PCR amplification of the DNA or mRNA source material is performed using forward primers containing a T7-promoter sequence and translation initiation signals such that the resultant products can be transcribed and translated in vitro to identify the smaller truncated protein products. mRNA is commonly used as the source material, but success of the PTT and other RNA-based mutation detection methods can be severely compromised by nonsense mutation-induced mRNA decay, a well-documented process that is often overlooked in mutation detection strategies. In this study, we develop an RNA-based PTT that overcomes the problem of mRNA decay by preincubating cells with cycloheximide to stabilise the mutant mRNA. The effectiveness of this method for mutation detection in abundant mRNAs was demonstrated in osteogenesis imperfecta fibroblasts by the protection of type I collagen (COL1A1) mRNA containing nonsense mutations that normally resulted in mutant mRNA degradation. Stabilisation of mutant mismatch repair gene (MLH1) mRNA was also observed in transformed lymphocytes from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Importantly, our strategy also stabilised very low-level (or illegitimate) nonsense-containing transcripts in lymphoblasts from patients with Bethlem myopathy (COL6A1), familial adenomatous polyposis (APC), and breast cancer (BRCA1). The greatly increased sensitivity and reliability of this RT-PCR/PTT protocol has broad applicability to the many genetic diseases in which only blood-derived cells may be readily available for analysis.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Two novel mutations of the FMO3 gene in a proband with trimethylaminuria.

The mammalian flavin-containing monooxygenases catalyze the NADPH-dependent N-oxygenation of nucleophilic nitrogen-, sulfur-, and phosphorus-containing chemicals, drugs, and xenobiotics, including trimethylamine. The FMO3 gene encodes the dominant catalytically active isoform present in human liver. We have identified two missense mutations in the coding region of the gene in a proband with trimethylaminuria (TMA): M66I and R492W. Whereas two mutations (P153L, E305X) accounted for TMA in our eight unrelated previously documented Australian families of British origin, the present report is the first evidence of compound heterozygosity for two rare mutations in a proband with this disorder. This suggests that other rarer alleles, also causing TMA, will be found in the same populations.

Adult↗
PubMed1999

Identifying genes predisposing to atopic eczema.

BACKGROUND: Genetic and environmental factors are known to play a role in the development of atopic diseases, such as asthma, eczema, and rhinitis. However, the atopy gene (or genes) has yet to be defined. Studies of familial asthma have identified several regions that may contain genes predisposing to atopy, but the data for candidate regions do not show agreement, which may be due to heterogeneity, ascertainment bias, or stochastic factors. Factors such as an early age of onset, a positive family history, and a clearly defined phenotype favor a genetic origin and improve the chance of identifying genes that predispose to atopy. OBJECTIVE: We sought to define genes that predispose to the development of atopic eczema. METHODS: We have studied nuclear families with multiple cases of early-onset atopic eczema for involvement of the candidate regions on chromosomes 5q31 (IL gene cluster), 11q13 (high-affinity FCepsilon receptor), 14q11.2 (mast cell chymase), and 16p12 (IL-4 receptor alpha-chain, IL4RA gene). RESULTS: Using a recessive model, we find a maximum parametric log of the odds of linkage score of 2. 25 and nonparametric score of 2.54 (P =.006) for a region on chromosome 5q31, which we postulate contains a gene predisposing to atopic eczema, but lack of support for linkage to 11q13. Transmission disequilibrium tests do not support an association with candidate polymorphisms in the mast cell chymase and IL4RA genes. CONCLUSION: We have identified a clinically homogeneous cohort of patients with atopic eczema to identify genetic factors predisposing to the development of atopy. We postulate that there are certain loci that predispose to atopy in general and other loci that determine which of the atopic phenotypes is expressed.

Adolescent↗
PubMed1999

Creativity on the edge of chaos.

The health care environment is chaotic, with many threats and problems. Despite nursing's resulting discomfort, being able to see the opportunities and the potential within such complexity is freeing. The author illustrates the use of creative thinking in formulating deliberate responses to the unpredictability of chaos. With such innovative actions, the essential nature of professional nursing can be reaffirmed.

Adaptation, Psychological↗
PubMed1999

Spinal muscular atrophy: untangling the knot?

Spinal muscular atrophy (SMA), a clinically and genetically heterogeneous group of neuromuscular diseases, is a disorder of motor neurones characterised by degeneration of spinal cord anterior horn cells and muscular atrophy. SMA is an autosomal recessive disorder with a carrier frequency of about 1150. Three candidate genes, the survival motor neurone (SMN) gene, the neuronal inhibitory protein (NAIP) gene, and the p44 (subunit of basal transcription factor TFIIH) gene, have been considered as genes involved in this condition. The region spanning these genes has a complex organisation including duplications, repetitive sequences, truncated genes, and pseudogenes, which makes molecular analysis of this condition difficult. Although deletions have been found in the majority of SMA patients, a few microrearrangements (like duplications, missense mutations, microdeletions, and gene conversions) localised in the telomeric form of the SMN gene have also been reported. The function of the protein encoded by the SMN gene is still not fully understood but recent studies have indicated that it is found intracellularly in gems, novel nuclear structures. Its interaction with other proteins suggests a role in mRNA processing and metabolism. Whether the NAIP gene protein and other apoptosis associated proteins are directly involved in the initial stages of neurone degeneration and apoptosis, or acting downstream on the pathological pathway, has been difficult to determine. Further studies will be required to elucidate possible functional interactions between these proteins.

Autoantigens↗
PubMed1998

Using lazy evaluation to simulate realistic-size repertoires in models of the immune system.

We describe a method of implementing efficient computer simulations of immune systems that have a large number of unique B- and/or T-cell clones. The method uses an implementation technique called lazy evaluation to create the illusion that all clones are being simulated, while only actually simulating a much smaller number of clones that can respond to the antigens in the simulation. The method is effective because only 0.001-0.01% of clones can typically be stimulated by an antigen, and because many simulations involve only a small number of distinct antigens. A lazy simulation of a realistic number of clones and 10 distinct antigens is 1000 times faster and 10,000 times smaller than a conventional simulation--making simulations of immune systems with realistic-size repertoires computationally tractable.

Algorithms↗
PubMed1998

The ideal role of the nurse teacher in the clinical area: a comparison of the perspectives of mental health, learning difficulties and general nurses.

This paper reports findings from a study that explored trained nurses' and student nurses' perceptions of the nurse teachers' ideal role in the clinical area. Findings demonstrate a dichotomy of opinion regarding the ideal role of the nurse teacher in the clinical area that relates to the nursing specialties in which trained nurses work. Trained nurses working in general nursing areas favoured a product-focused, inspectorate supervisory role for nurse teachers. Conversely, trained nurses working in mental health and learning difficulties areas favoured a supportive, supervisory role for the nurse teacher that emphasized the learning process and encouraged reflection. The consequence of the different models used for student nurses' experience of supervision are discussed and the issue of nurse teachers' clinical credibility is explored. It is suggested that trained nurses, nurse teachers and student nurses should be involved in negotiating and constructing the role that nurse teachers play in the clinical area.

Attitude of Health Personnel↗
PubMed1998

Molecular Basis of beta-Thalassemia in Indonesia: Application to Prenatal Diagnosis.

Background: To facilitate an effective prevention program, the beta-thalassemia mutations in the different ethnic groups in Indonesia were characterized. Methods and Results: The amplification refractory mutation system and artificially created restriction site were used to detect seven known mutations previously described in the Indonesian population. Other mutant alleles were identified by chemical cleavage mismatch, double-stranded sequencing, and Southern blotting. With these methods 78% of beta-thalassemia mutant alleles have been detected so far. Thirteen different beta-thalassemia mutations were characterized, nine of which had previously been described in the Jakarta population. The most frequent mutation is HbE (29%), followed by IVS1-nt5 (19%), and Cd 35 (8%). The frequencies of the other mutations varied from 4% to less than 1%. Two large gene deletions, Filipino beta-deletion and Hb Lepore, were identified in patients from the eastern part of Indonesia. Conclusions: The ethnicity and clinical hematology of cases in the region should be considered in the screening strategy for carriers and antenatal diagnosis of beta-thalassemia in Indonesia. Direct sequencing proved to be the appropriate method for detecting the unknown mutations, and Southern blotting had to be used for large deletions.

Journal Article↗
PubMed1997

Deriving shape space parameters from immunological data.

We present a method for deriving shape space parameters that are consistent with immunological data, and illustrate the method by deriving shape space parameters for a model of cross-reactive memory. Cross-reactive memory responses occur when the immune system is primed by one strain of a pathogen and challenged with a related, but different, strain. Much of the nature of a cross-reactive response is determined by the quantity and distribution of the memory cells, raised to the primary antigen, that cross-react with the secondary antigen. B cells with above threshold affinity for an antigen lie in a region of shape space that we call a ball of stimulation. In a cross-reactive response, the intersection of the balls of stimulation of the primary and secondary antigens contains the cross-reactive B cells and thus determines the degree of cross-reactivity between the antigens. We derive formulas for the volume of intersection of balls of stimulation in different shape spaces and show that the parameters of shape space, such as its dimensionality, have a large impact on the number of B cells in the intersection. The application of our method for driving shape space parameters indicates that, for Hamming shape spaces, 20 to 25 dimensions, a three or four letter alphabet, and balls of stimulation of radius five or six, are choices that match the experimental data. For Euclidean shape spaces, five to eight dimensions and balls of stimulation with radius about 20% of the radius of the whole space, match the experimental data.

Antigens↗
PubMed1997

Human flavin-containing monooxygenase form 3: cDNA expression of the enzymes containing amino acid substitutions observed in individuals with trimethylaminuria.

Trimethylaminuria is an autosomal recessive human disorder affecting a small part of the population as an inherited polymorphism. Individuals diagnosed with trimethylaminuria excrete relatively large amounts of trimethylamine in their urine, sweat, and breath, and this results in a fishy odor characteristic of trimethylamine. Activity of the human flavin-containing monooxygenase (FMO) has been proposed to be deficient in trimethylaminuria patients causing a decrease in the metabolism of trimethylamine that results in a fishy body odor. Cohorts of Australian, American, and British individuals suffering from trimethylaminuria have been identified. The human FMO3 cDNA was amplified from lymphocytes of affected patients. We report preliminary evidence of substitutions detected by screening of the cDNA and genomic DNA. The variant human FMO3 cDNA was constructed from wild type human FMO3 cDNA by site-directed mutagenesis as maltose-binding protein fusions. Five distinct human FMO3 mutants were expressed as fusion proteins in Escherichia coli and compared with wild type human FMO3 maltose-binding proteins (FMO3-MBP) for the N-oxygenation of 10-[(N,N-dimethylamino)pentyl]-2-(trifluoromethyl)phenothiazine, tyramine, and trimethylamine. Human Lys158 FMO3-MBP and, to a greater extent, human Glu158 FMO3-MBP efficiently N-oxygenated the three amine substrates. Human Lys158 Ile66 FMO3-MBP, Glu158 Ile66 FMO3-MBP, Lys158 Leu153 FMO3-MBP, and Glu158 Leu153 FMO3-MBP were all constructed as mutants identified as possible FMO3 variants responsible for trimethylaminuria and were found to be inactive as N-oxygenases. The results suggest that mutations at codons 66 and 153 of FMO3 can cause trimethylaminuria in humans. We observed a common polymorphism of Lys to Glu at codon 158 of FMO3 that segregated with almost equal allele frequencies in a number of control Australian and North American samples studied. The Lys158 to Glu158 human FMO3 polymorphism does not decrease trimethylamine N-oxygenation for the cDNA-expressed enzyme and thus does not appear to be causative of trimethyaminuria. The data show that the functional activity of human FMO3 can be significantly altered by amino acid changes that have been observed in individuals with clinically diagnosed trimethylaminuria.

DNA, Complementary↗
PubMed1997

Modified Method for the Detection of the CAG Repeat Expansion in Huntington's Disease and Application to a Predictive Testing Protocol.

Background: The identification of the CAG trinucleotide repeat expansion as the cause of Huntington's disease (HD) has dramatically altered the ease and uptake of testing. The direct test for the mutation allows testing of many more consultands, particularly those individuals whose family structure is not suitable for linkage analysis. Therefore, protocols that can rapidly handle a number of samples and give accurate reliable results are essential. Methods and Results: The HD1/HD2 set of primers, which amplify the variable CAG and polymorphic CCG repeats, and the HD1/HD3 set of primers, which amplify only the variable CAG repeat, were used. Comparison of internally labeled with end-labeled polymerase chain reaction product was made. "Lysates" made from blood were investigated as suitable material for the HD polymerase chain reaction. Conclusions: The conditions used for detection of the CAG repeat in the huntingtin gene by end labeling of one of the primers that amplifies only the CAG repeat were improved, and an efficient protocol that reduces sample preparation and storage by using lysates from blood rather than extracted purified genomic DNA was developed.

Journal Article↗