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Biomedical subjects

S Forrest

Publications and source records attributed to S Forrest.

47 records · Page 3Linked to original sources
PubMed1993

Genetic algorithms for DNA sequence assembly.

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.

Algorithms↗
PubMed1990

Methods of detection of single base substitutions in clinical genetic practice.

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.

Base Composition↗
PubMed1989

Possibilities and limitation of prenatal diagnosis and carrier determination for Duchenne and Becker muscular dystrophy using cDNA probes.

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.

Chromosome Deletion↗
PubMed1988

Suicide and the rural adolescent.

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.

Adolescent↗
PubMed1986

Regional localisation of X chromosome short arm probes.

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.

Chromosome Banding↗
PubMed1984

Comparison of substrate specificity of myosin kinase and cyclic AMP-dependent protein kinase.

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.

Amino Acids↗
PubMed1979

Sensorimotor rhythm feedback training and epilepsy: some methodological and conceptual issues.

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.

Adult↗
PubMedDate not supplied

Contracting in the NHS quasi-market.

This paper examines the development of contracting within the NHS on the basis of the data collected as part of a national survey of English District Health Authorities carried out in late 1994. The paper starts with a discussion of the background to contracting and its evolution during the first 4 years of the NHS internal market. The second section describes the methodology employed in the national survey. The third section presents the results of the survey alongside a discussion of their relevance in terms of the economics of contracting. This section shows the prevalence of different types of contracts and discusses the emergence of the most common type-sophisticated block contracts. Details are provided of how contracts deal with issues such as the measurement of activity, the pricing of projected activity and of activity variances (mainly at marginal cost), as well as the involvement of clinicians in contracting. Other topics explored include the management of extra contractual referrals, contracting for specialized services, arbitration arrangements, the purchaser efficiency index and contracts with the independent sector. The final section offers some concluding thoughts on the current state and future of contracting in the NHS.

Contract Services↗
PubMedDate not supplied

Molecular analysis of human muscular dystrophies.

The ability to map disease loci using restriction fragment length polymorphisms (RFLPs) identified by DNA probes has revolutionized molecular genetics. Duchenne and Becker muscular dystrophies have been shown to be localized within the same very small region of Xp21 on the human X chromosome. The mutation itself should soon be identified at the DNA level, which will permit a detailed analysis of the molecular defect at the biochemical level. Rapid progress has also been made in the study of myotonic dystrophy on chromosome 19. DNA markers closely linked to the mutant locus have been identified, making antenatal diagnosis possible in informative families. Autosomal recessive muscular dystrophies are more difficult to study, but the means to localize even these mutations is being developed. The next decade should prove to be an exciting one for those involved in the molecular analysis and clinical management of human muscular dystrophies.

Chromosome Mapping↗
PubMedDate not supplied

Toward understanding the self.

Others may know "me" but only "I" am the knower of myself. The metaparadigm of nursing includes four concepts: health, environment, nurse, and person. Each concept is complex and can be interpreted in diverse ways. The concept analysis in this article focuses on one aspect of person, specifically "self:" its birth, development, and loss. The author makes suggestions for using the analysis in nursing education, theory development, and clinical practice in caring for and promoting the health of individuals, groups, and families.

Adolescent↗