Campaign tackles family violence epidemic.
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Community-Institutional Relations↗
Biomedical subjects
F Williams
Publications and source records attributed to F Williams.
Effect of carbohydrate ingestion and hormonal responses on ratings of perceived exertion during prolonged cycling and running.
This randomized, double-blind, placebo-controlled study was designed to determine the influence of exercise mode, and 6% carbohydrate (C) versus placebo (P) beverage ingestion, on ratings of perceived exertion (RPE) and hormonal regulation to 2.5 h of high-intensity running and cycling (approximately 75% maximum oxygen uptake) by ten triathletes who acted as their own controls. Statistical significance was set at P < or = 0.05. The pattern of change in RPE over time was significantly different between C and P ingestion (P < 0.001) and between running and cycling modes (P = 0.001). The lowest RPE values were seen in the C-cycling sessions and the highest in the P-running sessions. The pattern of change in the respiratory exchange ratio and fat and carbohydrate oxidation rates were significantly different between the C and P conditions but not between the running and cycling modes. C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin and lower plasma cortisol and growth hormone levels. The pattern of change in plasma levels of catecholamines and lactate did not differ between the C and P conditions. These data indicate that a lower RPE was associated with a higher level of carbohydrate oxidation, higher plasma glucose and insulin levels, and lower plasma cortisol and growth hormone levels during cycle exercise following C supplementation as compared to P feeding. These findings support a physiological link between RPE and carbohydrate substrate availability as well as selected hormonal regulation during cycle exercise.
Adult↗
Aberrant splicing of intron 1 creates a novel null HLA-B*1501 allele.
A comparison of serological and DNA HLA class I typing data identified a serological "blank" HLA-B15 antigen in a volunteer donor on the bone marrow registry. Isoelectric focusing and Western blot analysis of a cell line established from this individual confirmed that the HLA-B15 antigen is not expressed at the cell surface. Nucleotide sequence analysis of the HLA-B*15 null allele revealed a 10-bp deletion near the 3' end of intron 1, when compared to the normal HLA-B*1501 sequence. All of the HLA-B*15 specific cDNA clones examined retained the intron 1 sequence. Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis demonstrated that the HLA-B*15 mRNA molecule contained the intron 1 sequence, indicating an inability to efficiently splice out intron 1 from the mRNA transcript. The retention of the mutated intron 1 sequence in the mRNA causes a frameshift and premature termination of translation at the start of exon 2, explaining the HLA-B*1501 null phenotype. Our data predicts that the HLA-B*1501 null allele would express a small truncated protein containing the signal sequence fused to an ORF within intron 1 and terminating (out of frame) just within exon 2.
Alleles↗
Molecular analysis of HLA class I alleles in the Mexican Seri Indians: implications for their origin.
The molecular analysis of HLA class I loci has demonstrated that, although, the genetic profile is restricted in Amerindians, several micropolymorphisms may be important in conferring a biological advantage. We analyzed the HLA-A and B genetic profile of Seris, a Mexican Indian tribe living in northwestern Mexico in the state of Sonora. There are presently only 619 individuals. Our study included 100 Seris belonging to nine families. HLA-A and -B loci typing was performed by polymerase chain reaction using an amplification refractory mutation system (PCR-ARMS) on a select group of samples; all of them were typed by polymerase chain reaction using sequence-specific oliogonuoleotide probes (PCR-SSOP) at a low-intermediate resolution level. The correlation between the techniques was 100%. Only five HLA-A alleles and seven HLA-B alleles were found. A*0201, A*68, A*31, A*24, B*3501, B*40, B*51, B*3512 and B*15 were present in over 5% of the individuals. B*27052 was detected in 2%. B27 is absent in any other Mexican Indian groups previously studied. The presence of B27 may be the result of a founder effect due to different waves of southward migrations. The B-locus is more diverse and the prevalent haplotypes were: A*0201-B*3501, A*0201-B*40, A*0201-B*3512, A*31-B*51, A*68-B*3501 and A*68-B*40. This genetic profile is different from the pattern of other Mexicans. The phylogenetic tree suggests that Seris are more closely related to the Warao Indians from Venezuela, who live in a similar ecosystem, and to some groups of Argentina, than they are to the Mexican Lacandones who live in the jungle. These data emphasize the relevance of the interaction between genes and environment.
Genetics, Population↗
Allele resolution of HLA-A using oligonucleotide probes in a two-stage typing strategy.
High-resolution polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP) typing methods for HLA-A identification have been established. The four systems, which operate independently of each other, are intended for use as secondary typing systems following HLA-A identification with a medium-resolution PCR-SSOP technique. The systems, all using digoxigenin-labelled probes, are based on group specific amplifications for resolution of: i) HLA-A*29 & -A*33; ii) HLA-A*24 & -A*30; and iii) HLA-A*26, -A*25, -A*11, -A*34, -A*66 and -A*68 alleles, respectively. The fourth system, for the detection of HLA-A*02 alleles, is a modification of a previously reported PCR-SSOP subtyping system. The methods have been applied to individuals from the local bone marrow registry and HLA-A allele frequencies for the Northern Ireland population have been established.
Alleles↗
Improvements to HLA-B*27 testing.
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Genetic Testing↗
Characterisation of a novel HLA-A pseudogene, HLA-BEL, with significant sequence identity with a gorilla MHC class I gene.
During the development of an HLA-A polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP) method for the identification of HLA-A*24 and -A*30 alleles, group amplification resulted in the formation of an unusual PCR product in certain individuals. This fragment was approximately 900 bp smaller than the expected product and was also detected in some non-HLA-A*24- and -A*30-positive individuals acting as negative controls for the group specific amplification. Nucleotide sequence analysis of this product identified it as a unique class I gene sequence displaying homology to both primate and human class I A-locus genes. The entire gene was amplified using PCR and the complete DNA sequence information from exon 1 to exon 8, including introns, was determined. A recombination event was identified which results in the fusion of intron 2 with intron 3, causing a deletion of the intervening exon 3 sequence. In addition, there are two cytosine insertions in the poly-cytosine stretch at the start of exon 4 which cause a frameshift and premature termination. The exon 1 and 2 sequences most closely align with the gorilla allele A*0501, displaying only five mismatches. PCR analysis has established that the gene is associated with the following HLA-A types: HLA-A*3001, -A*3301, -A*3303, -A*6802, -A*2901, -A*0203, -A*0205 and -A*31012. Reverse transcription (RT)-PCR analysis of individuals containing this gene failed to detect any mRNA transcription, suggesting that this is a previously undescribed non-expressed class I pseudogene which we have provisionally named HLA-BEL. Its unique gene structure gives a possible insight into the evolutionary pathway that created HLA class I genes.
Alleles↗
How counselling psychologists view their personal therapy.
A survey of UK chartered counselling psychologists (N = 192) was carried out to investigate how they viewed their personal therapy. Eighty-four respondents completed questionnaires about their reasons and motivations for therapy, as well as its outcome and process. The results indicated that the majority (88%) were in favour of personal therapy as a training requirement. Most respondents rated the outcome and process of their personal therapy as positive, however 27% also reported some negative effects. A factor analysis of various components of personal therapy indicated that counselling psychologists made a distinction between three factors, i.e. learning about therapy itself, issues arising out of training and dealing with personal issues. Analyses of the data suggested that aims and motivation for therapy were related to dealing with personal issues, whereas these were not important for the other factors. Learning about therapy itself was related to the number of sessions: more specifically, those who had more than the mandatory 40 sessions rated contributions of their personal therapy to understanding therapeutic relationships and processes more highly than those who had less. Initial sessions may be used by trainees to explore personal issues, leading to a preoccupation with the self, and learning about therapy per se may only occur once this has been dealt with.
Adult↗
Comparison of the characteristics and features of pressure garments used in the management of burn scars.
Two companies provide custom-made pressure garments to clients with burn scars at Westmead Hospital. This prospective study was completed in order to make objective decisions about which garments were most appropriate and cost effective to provide to clients. Issues such as cost, durability, fit and client preferences were investigated. Data were collected from 43 clients; at the time of initial fitting, at a follow-up appointment 4-6 weeks later, and at the time one of the garments required replacement. One Second Skin and one Jobst garment were provided to each client and the garments were compared using therapists' evaluation and clients' perspectives on a number of variables. Second Skin garments had significantly more favourable results on the variables of time for delivery, fit at follow-up, garment design, quality of fabric and seams, overall satisfaction and garment preference for ongoing wear. On all other variables there was no significant difference between the garments. Second Skin provided the most optimal and appropriate option for pressure garments in the management of burn scars for our clients.
Adolescent↗
Influence of mode and carbohydrate on the cytokine response to heavy exertion.
OBJECTIVE AND METHODS: This randomized, double-blind, placebo-controlled study was designed to determine the influence of exercise mode and 6% carbohydrate (C) versus placebo (P) beverage ingestion, on blood cell counts, plasma glucose, hormone, and inflammatory cytokine responses (five total samples over 9 h) to 2.5 h of high-intensity running and cycling (approximately 75% VO2max) by 10 triathletes who acted as their own controls. Statistical significance was set at P < or = 0.05. RESULTS: C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin, lower plasma cortisol and growth hormone, and diminished perturbation in blood immune cell counts. The pattern of change over time for interleukin (IL)-6 was significantly different between C and P conditions (P = 0.021) and between running and cycling modes (P < 0.001), with the lowest postexercise values seen in the C-cycling sessions (10.7 +/- 1.8 pg x mL(-1)) and the highest in the P-running sessions (51.6 +/- 14.2 pg x mL(-1)). The pattern of change over time between C and P conditions (but not modes) was significantly different for IL-1 receptor antagonist (P = 0.003), with values once again lowest for the C-cycling sessions (1.5 h postexercise, 301 +/- 114 pg x mL(-1)) and highest for the P-running sessions (1171 +/- 439 pg x mL(-1)). CONCLUSION: These data indicate that carbohydrate versus placebo ingestion (4 mL x kg(-1) carbohydrate or placebo every 15 min of the 2.5-h exercise bout) is associated with higher plasma glucose levels, an attenuated cortisol response, and a diminished pro- and anti-inflammatory cytokine response.
Adult↗
HLA-A towards a high-resolution DNA typing.
Sequencing-based typing (SBT) and sequence-specific oligonucleotide probing (PCR-SSOP) are DNA-based typing approaches to identify HLA-A alleles. In this study PCR-SSOP SBT have been evaluated and considered to reach a high-resolution typing. Based upon serological typing, 32 genomic samples were typed by SBT and PCR-SSOP Three main clusters of resolution could be defined. The advantage of the PCR-SSOP approach is the possibility to type numerous samples in a short time. SBT minimizes the number of ambiguous heterozygous combinations and often allows direct detection and identification of new alleles.
DNA↗
Detection of HLA-A*24 null alleles by DNA typing methods.
A number of cases have been identified (seven unrelated individuals from the Northern Ireland bone marrow donor registry and two family groups) where an HLA-A*24 allele fails to express the normal HLA-A24 antigen. Family information has revealed common haplotypes with respect to each non-expressed allele indicating that the occurrence of these mutations has been a recent event. Two methods for the clinical typing of these alleles have been evaluated--PCR-SSOP and PCR-SSCP analysis.
Base Sequence↗
Effects of mode and carbohydrate on the granulocyte and monocyte response to intensive, prolonged exercise.
The influence of exercise mode and 6% carbohydrate (C) vs. placebo (P) beverage ingestion on granulocyte and monocyte phagocytosis and oxidative burst activity (GMPOB) after prolonged and intensive exertion was measured in 10 triathletes. The triathletes acted as their own controls and ran or cycled for 2.5 h at approximately 75% maximal O2 uptake, ingesting C or P (4 total sessions, random order, with beverages administered in double-blind fashion). During the 2. 5-h exercise bouts, C or P (4 ml/kg) was ingested every 15 min. Five blood samples were collected (15 min before exercise, immediately after exercise, and 1.5, 3, and 6 h after exercise). The pattern of change over time for GMPOB was significantly different between C and P conditions (P </= 0.05), with postexercise values lower during the C trials. Little difference was measured between running and cycling modes. C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin, lower plasma levels of cortisol and growth hormone, and lower blood neutrophil and monocyte cell counts. These data indicate that C vs. P ingestion is associated with higher plasma glucose levels, an attenuated cortisol response, and lower GMPOB.
Adult↗
Natural inactivation of a common HLA allele (A*2402) has occurred on at least three separate occasions.
HLA-A*2402 is common and widely distributed in human populations. Several individuals were identified who type genotypically for A*2402, but are serologically null for the HLA-A24 Ag. Sequencing and transfection of genomic DNA fragments containing null and wild-type A*2402 alleles, and the related A*2301 allele, revealed three different null alleles (A*2409N, A*2411N, and A*2402(low)), each of which differs from A*2402 by a single nucleotide change within the 6.7-kb sequence. The A*2301 and A*2402 sequences differ by no substitutions additional to those previously determined for the 1.1-kb cDNA. In exon 4, A*2409N has an in-frame stop codon, while A*2411N has a nucleotide insertion that alters the reading frame, causing premature termination. A*2402(low) has a nucleotide substitution near the splice acceptor site for intron 2 that impairs the production of correctly spliced mRNA. For A*2409N and A*2411N, mRNA is undetectable by Northern analysis, whereas A*2402(low) produces a low level of mRNA and a concomitant amount of normal A*2402 protein at the cell surface. The protein expressed from the A*2402(low) allele is sufficient to stimulate an alloreactive T cell response. On a background of unexpected sequence homogeneity, the single nucleotide changes in the A*2409N, A*2411, and A*2402(low) alleles have dramatic effects upon gene expression and are of likely importance for HLA matching in clinical transplantation. Segregation of at least three independently inactivated A*2402 alleles in human populations raises the possibility that loss of A*2402 may be the result of natural selection.
Alleles↗
Application of an HLA-B PCR-SSOP typing method to a bone marrow donor registry.
A previously reported HLA-B PCR-SSOP typing method has been applied to those individuals, from the local bone marrow registry, with only one detectable HLA-B antigen by serology. The PCR-SSOP method detected the serologically defined HLA-B antigen in all cases. In addition, PCR-SSOP detected the presence of a second HLA-B allele in 19.9% of these individuals. The method was also applied to all individuals where serology could only determine the HLA-B antigen as a broad specificity. All antigens were split by the PCR-SSOP method, indicating that the method is more specific than serology. Using a combination of PCR-SSOP and serologically determined types for 5000 individuals on the local bone marrow registry, HLA-B frequencies for the Northern Ireland population have been calculated.
Alleles↗
Development of PCR-SSOP for HLA-A typing of bone marrow registry donors.
A medium resolution PCR-SSOP typing method, using 26 digoxigenin labelled probes, has been established for the identification of HLA-A alleles. The system is capable of discriminating all of the serologically defined specificities except for eight heterozygous combinations which are however rare in Caucasians. The method has been applied to 1,838 individuals on the local bone marrow registry who either had only one detectable HLA-A antigen, or a HLA-A antigen whose presence had been queried using the serological technique or a broad HLA-A specificity assigned by the serological technique. In all but one case the serologically assigned antigens were detected with the PCR-SSOP method. In addition, PCR-SSOP detected the presence of a second HLA-A allele in over 10% of individuals who had been previously homozygous. Frequency information, based on a population of 5,000 individuals, has been established using a combination of molecular and serological typing data.
Bone Marrow↗
Development of PCR-SSOP for the identification of HLA-A*02 subtypes and determination of HLA-A*02 frequencies within different ethnic populations.
A PCR-SSOP typing method, involving a single PCR amplification in conjunction with 19 digoxigenin labelled oligonucleotide probes, has been developed for the identification of 17 known HLA-A*02 alleles. The method has been applied to four populations (Northern Ireland, Singapore Chinese, Shetland Island and Mexican) and percentages of HLA-A*02 alleles determined within each population.
Alleles↗
Identification of a new HLA-B allele, HLA-B*0708.
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Alleles↗