Evolution and somatic learning in V-region genes.
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Biomedical subjects
Publications and source records attributed to S Forrest.
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This paper describes a study which aimed to explore the present and ideal role of the nurse teacher in the clinical area from the perspective of: nurse teachers; ward sisters/charge nurses; staff nurses and students nurses undertaking the 'traditional' and Project 2000 programmes of training. The study adopted a qualitative design. Findings from this study demonstrate that the clinical role of the nurse teacher lacks clarity, however, clear criteria emerged as to how trained nurses and student nurses perceived the ideal role. Nurse teachers' role in assuring the quality of the clinical learning environment emerged as a major area of criticism. It was suggested that, if nurse teachers adopted a clinical role that was primarily concerned with supporting clinically based nurses in their teaching role, this served to assure the quality of students' clinical learning experience. In conclusion, it is suggested that for nurse teachers to meet the needs of trained nurses and student nurses in the clinical area, the role must be diverse and flexible. Attempts to prescribe a unimodel approach to deliver the service should be avoided. Rather, the role must be negotiated between teachers, clinical nurses and students, and constructed in a way that best meets the needs of all parties concerned.
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Newborn screening for cystic fibrosis (CF) by examining the levels of immunoreactive trypsinogen was introduced in Victoria in 1989. This was modified by the addition of testing for the common CF gene mutation, delta F508, in 1990. Problems with the first newborn screening protocol were overcome with the addition of the DNA test as there was no need to contact the majority of families, there was a reduced number of sweat tests, and less anxiety was experienced by parents. The mode of diagnosis changed from failure to thrive, steatorrhoea, rectal prolapse, and family history to diagnosis through newborn screening. Newborn screening dramatically reduced the time of diagnosis of CF to approximately six weeks or less in the majority of cases. Since the introduction of newborn screening, the uptake of prenatal diagnosis in CF families has increased two and a quarter fold.
The paper reports on issues of methodology regarding the evaluation of residential care for mentally ill people. A literature review examines the development of research approaches to studying residential care practices, from qualitative descriptive studies to quantitative comparative studies. The difficulty of definition and measurement in high-quality residential care is discussed. Findings are presented from an ethnographic study of care structure and process, and the experience of staff and clients, conducted in two residential care settings. Anomalies are reported in the use of quantitative and qualitative research methods. There is a discussion of methodological issues that arise from anomalous findings.
A genetic algorithm is a form of evolution that occurs on a computer. Genetic algorithms are a search method that can be used for both solving problems and modeling evolutionary systems. With various mapping techniques and an appropriate measure of fitness, a genetic algorithm can be tailored to evolve a solution for many types of problems, including optimization of a function of determination of the proper order of a sequence. Mathematical analysis has begun to explain how genetic algorithms work and how best to use them. Recently, genetic algorithms have been used to model several natural evolutionary systems, including immune systems.
OBJECTIVE: To ascertain and characterize rhodopsin gene mutations in autosomal dominant retinitis pigmentosa and to correlate these mutations with the clinical phenotypes. METHODS: DNA was extracted from leukocytes, and the rhodopsin gene was amplified and analyzed using molecular-biological methods. Clinical and electrophysiological data were collected from patient charts. RESULTS: We found a disease-causing mutation that was previously undescribed, to our knowledge, for autosomal dominant retinitis pigmentosa within codon 15 of exon 1 of the rhodopsin gene. It was a single base-pair transversion (AAT to AGT) leading to a serine-for-asparagine substitution. This altered a glycosylation site in the intradiscal portion of the rhodopsin molecule. The pedigree examined demonstrated an inferior distribution of retinal pigmentary changes and predominantly superior visual field loss with relative preservation of electroretinographic amplitudes and good vision, which is consistent with sectorial or sectorial-like retinitis pigmentosa. CONCLUSIONS: A codon 15 rhodopsin gene mutation caused retinitis pigmentosa in the pedigree studied. There may be an association between intradiscal rhodopsin gene mutations and sectorial forms of retinitis pigmentosa.
Osmium tetroxide and hydroxylamine are used to detect mutations in DNA and RNA after hybridization of mutant and wild-type DNA. Mismatched T and C bases, respectively, are modified by these reagents and the DNA strand cleaved at the mismatched bases by subsequent treatment with piperidine. This allows detection and location of the mutation. Although most T.G mismatches have been reported to be reactive to osmium tetroxide, some have been reported to be unreactive. The aim of this study was to collect and analyze the reactive and unreactive T.G mismatches. We have collected sequence contexts of all reactive and unreactive T.G mismatches for analysis. This involves 10 unreactive T.G mismatches (plus one T.C) and 19 reactive T.G mismatches. Sequence effects of bases surrounding these mismatches must influence this reactivity. There must be many types of such sequence effects. We postulate that because of the dominance of 5' G bases near the T of unreactive T.G mismatches and the absence of 5' G bases in reactive T.G mismatches that the stacking of the 5' G on the mismatched T is the reason for this lack of reactivity in the majority of the cases studied here.
Individuals from 33 unrelated Australian families with optic atrophy were screened for 10 different single base alterations in mitochondrial DNA (mtDNA) associated with Leber hereditary optic neuropathy (LHON) using direct polymerase chain reaction amplification of blood spots collected on Guthrie cards. This method using blood spots allows easily accessible screening for LHON mtDNA mutations with minimal biohazard risk and reduced expense in the storage and transport of specimens.
This paper describes a genetic algorithm application to the DNA sequence assembly problem. The genetic algorithm uses a sorted order representation for representing the orderings of fragments. Two different fitness functions, both based on pairwise overlap strengths between fragments, are tested. The paper concludes that the genetic algorithm is a promising method for fragment assembly problems, achieving usable solutions quickly, but that the current fitness functions are flawed and that other representations might be more appropriate.
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The ability to diagnose human diseases at the DNA level has become possible because of a rapid development in DNA technology, particularly in the area of detection of single base substitutions. Mutations in the genomic DNA of a particular gene may be inferred indirectly using linkage analysis and restriction fragment length polymorphisms. However, direct detection of the mutation is the more favourable approach. The advent of the polymerase chain reaction to amplify specific regions of genomic DNA or mRNA has enhanced the speed and sensitivity of many of the screening and diagnostic procedures. Screening methods have been developed that will detect at least 70% and, with some methods, close to 100% of all mutations. The methods include ribonuclease A cleavage, denaturing gradient gel electrophoresis, chemical cleavage of mismatch and direct sequencing. Choice of method is based on a number of factors and will depend on the structure of the gene to be analysed. Following identification of a mutation using one of the screening procedures, prenatal diagnosis and carrier testing can be offered. The overall aim is to develop a method that has the potential to determine the mutation present in an index case of a previously untested family in a few days, thus allowing any other relevant family member to be tested.
Two cDNA probes, cf23a and cf56a, identify deletions of selected exons in about 50% of our DMD/BMD patients. We have estimated the most likely order of the 11 exons detectable with both probes with respect to the different extensions of the deletions. In one of our BMD pedigrees, the observed deletion could be traced in the affected males through three generations. This result shows that with the use of cDNA probes detecting deletions, the only risk of error in genomic prenatal diagnosis is the general high frequency of new mutations for DMD/BMD. This is important progress in diagnosis compared to the 2 to 5% risk of misdiagnosis because of crossing over events using conventional linkage analysis with bridging or intragenic probes. The first prenatal diagnosis of an unaffected fetus of a woman who is a DMD carrier according to ultrasound examination is described. In one of our DMD males, the cDNA probe cf56a detects a deletion breakpoint. His sister also shows the altered band and is therefore a DMD carrier, while his mother has a totally normal band pattern. The interpretation of this observation could be either germline mosaicism or two identical new mutations. The identification of deletion breakpoints is a new diagnostic strategy, especially for carrier determination, which excludes misdiagnosis owing to crossing over events and the problems of dosage estimation. It is, however, limited by the low frequency of breakpoints detectable with cDNA probes. Therefore, the generation of new intron probes in this region is an important goal.
The rural family, with its particular stressors, is increasingly vulnerable to overwhelming crises. Adolescent suicide, although rare, may result from or add to that stress. The intent of this study was to identify and examine specific stressors with which a rural adolescent must deal, the coping mechanisms utilized, and when these fail, how it leads to suicidal behavior. Therapeutic modalities available to the troubled adolescent were examined and additional services suggested.
Nine human X chromosome-specific clones have been isolated by screening an X-chromosomal genomic library with fetal muscle cDNA. Five of the clones have been localised to the short arm and four to the long arm. The short arm probes have been regionally assigned using a panel of somatic cell hybrids. They have been mapped further using a series of DNA samples from male patients with different deletions of the region Xp21, and having complex phenotypes including Duchenne muscular dystrophy. The use of these probes in the mapping of the short arm of the X chromosome is discussed.
A series of synthetic peptides corresponding to the amino-terminal region of chicken gizzard myosin light chain (Mr 20 000) have been tested for their capacity to act as substrates for the cAMP-dependent protein kinase. The 18-residue peptide, K6AKTTK11 K12R13PQRATS19NVFS , was stoichiometrically phosphorylated on serine-19 by the cAMP-dependent protein kinase. This is the same residue phosphorylated by the myosin light chain kinase. The cAMP-dependent protein kinase phosphorylated this peptide with an apparent Km of 120 microM and Vmax of 0.29 mumol . min .-1 mg-1. The Km is 17-fold higher and the Vmax 10-fold lower than the corresponding values obtained with this peptide as substrate for the myosin light chain kinase. The kinetics of phosphorylation of shortened peptides corresponding to this 18-residue sequence together with those of another related sequence, RPQRAKAKTTKATSNVFS , indicated that the myosin light chain kinase had a relatively stronger dependence on lysine residues, whereas the cAMP-dependent protein kinase depends more on arginine residues. Although both the cAMP-dependent protein kinase and the myosin light chain kinase phosphorylate the same serine in the myosin light chain peptides, these enzymes are influenced by different nearby basic residues.
This study examined the hypothesis that the enhancement of a 12-16 Hz sensorimotor rhythm in the EEG is inhibitory to epileptic seizure activity. The effects of training to enhance 12-16 Hz central EEG, to enhance 8-10 Hz central EEG, to suppress high voltage EEG activity, and of random feedback were compared over a period of 12 months in three adult patients suffering from chronic, drug-refractory epilepsy. All three patients experienced a significant reduction in seizure rate by the end of the study, but this was not related to any one particular training condition. It is suggested that the therapeutic mechanism might involve placebo effects, relaxation training, or a facilitation of EEG desynchronization, the effect being idiosyncratic to the individual patient.