PubMed Health⌕ Search

Biomedical subjects

T J Parsons

Publications and source records attributed to T J Parsons.

At least 19 recordsLinked to original sources

Analysis of artificially degraded DNA using STRs and SNPs--results of a collaborative European (EDNAP) exercise.

Recently, there has been much debate about what kinds of genetic markers should be implemented as new core loci that constitute national DNA databases. The choices lie between conventional STRs, ranging in size from 100 to 450 bp; mini-STRs, with amplicon sizes less than 200 bp; and single nucleotide polymorphisms (SNPs). There is general agreement by the European DNA Profiling Group (EDNAP) and the European Network of Forensic Science Institutes (ENFSI) that the reason to implement new markers is to increase the chance of amplifying highly degraded DNA rather than to increase the discriminating power of the current techniques. A collaborative study between nine European and US laboratories was organised under the auspices of EDNAP. Each laboratory was supplied with a SNP multiplex kit (Foren-SNPs) provided by the Forensic Science Service, two mini-STR kits provided by the National Institute of Standards and Technology (NIST) and a set of degraded DNA stains (blood and saliva). Laboratories tested all three multiplex kits, along with their own existing DNA profiling technique, on the same sets of degraded samples. Results were collated and analysed and, in general, mini-STR systems were shown to be the most effective. Accordingly, the EDNAP and ENFSI working groups have recommended that existing STR loci are reengineered to provide smaller amplicons, and the adoption of three new European core loci has been agreed.

Analysis of Variance↗

Changes in diet and physical activity in the 1990s in a large British sample (1958 birth cohort).

OBJECTIVES: To investigate whether adults studied in 1991 and 1999 (at ages 33 and 42 y) improved their diet and their physical activity level, in the direction of recommendations issued during the same period. DESIGN: Longitudinal 1958 British birth cohort study. SETTING: England, Scotland and Wales. PARTICIPANTS: All births, 3rd-9th March, 1958. A minimum of 11 341 participants provided data at 33 y, 11 361 at 42 y. MAIN OUTCOME MEASURES: Frequency of leisure time activity and consumption of (i) fried food, (ii) chips, (iii) wholemeal bread and (iv) fruit and salad/raw vegetables, at 33 and 42 y. RESULTS: Most people changed their physical activity and dietary habits over the 8-y period. About a third of men and women increased, and a third decreased their activity frequency. Findings for fried food consumption were similar. A significantly greater proportion of cohort members decreased their chips consumption (32%), rather than increased it (17%) and increased their fruit and salad consumption (30%), rather than decreased it (25%). In all, 26% of men and 33% of women consistently ate, or switched to eating mostly wholemeal bread, while 56% of men and 48% of women consistently ate less or switched to eating less. Social gradients were seen for activity and diet in 1991, but associations between social factors or body mass index and change in activity or diet were inconsistent. CONCLUSIONS: Lifestyle habits such as dietary intake and physical activity are slow to change. Current health promotion strategies may need to be supplemented with additional methods to affect the desired change in these habits.

Adult↗

Physical activity, television viewing and body mass index: a cross-sectional analysis from childhood to adulthood in the 1958 British cohort.

OBJECTIVE: To investigate relationships between frequency of physical activity or television viewing and body mass index (BMI) cross-sectionally at six ages from childhood to adulthood, to better understand longitudinal relationships. To investigate how the relationships vary with age and gender and whether any relationships are due to confounding factors. METHODS: The 1958 British birth cohort includes all births (approximately 17 000) in one week in March 1958. BMI and physical activity frequency were recorded at 11, 16, 23, 33 and 42 y and television viewing frequency at 11, 16 and 23 y. A total of 11 109 subjects provided BMI and activity data at 42 y. Relationships between BMI and (in)activity were investigated using linear regression. RESULTS: At ages 11, 33 and 42 y in both sexes and at 23 y in female subjects, those who were more active had lower BMIs, and the relationships strengthened with age. At 42 y, the most active had a lower mean BMI than the least active, by 0.83 kg/m2 in men, and 1.03 kg/m2 in women. BMI and activity were unrelated at 16 y in female subjects, and 23 y in male subjects. At 16 y in males, the most active males had a mean BMI 0.25 kg/m2 higher than the least active. At 11 y in female subjects and 23 y in both sexes, those who watched television most frequently had higher BMIs. BMI and television viewing were unrelated at 11 y in males and at 16 y in both sexes. Relationships between BMI and activity or television viewing were largely unexplained by potential confounding factors. CONCLUSIONS: The relationship between BMI and physical activity changes with age. In early adolescence and in adulthood, a higher activity level, or lower frequency of television viewing was associated with a lower BMI. In later adolescence (16 y), television viewing and activity were unrelated to BMI, except for an unexpected BMI-activity relationship in males. We suspect this relationship in males is primarily due to selection effects, whereby physically bigger boys, with a larger BMI, are more likely to take part in exercise activity, and possibly also to BMI being a less accurate predictor of fatness in adolescent boys.

Activities of Daily Living↗

Infant feeding and obesity through the lifecourse.

In the 1958 British birth cohort (n = 12,857 at age 7), breast feeding and BMI were unrelated in childhood. Breast feeding was protective against increased BMI at ages 16 and 33 years in females, and at 33 years in males, but this effect was markedly reduced and no longer significant after adjustment for confounding factors.

Adolescent↗

A new database of mitochondrial DNA hypervariable regions I and II sequences from 162 Japanese individuals.

A database of mitochondrial DNA (mtDNA) hypervariable region 1 (HV1) and region 2 (HV2) sequences of the mtDNA control region was established from 162 unrelated Japanese individuals. The random match probability and the genetic diversity for this database were 0.96% and 0.997, respectively. Length heteroplasmy in the C-stretch regions located around position 16189 in HVI and 310 in HV2 was observed in 37% and 38% of the samples, respectively. A strategy using internal sequencing primers was devised to obtain confirmed sequences in these length heteroplasmic individuals. This database, combined with other mtDNA sequence databases from the Japanese population, will permit the significance of mtDNA match results to be properly reported in mtDNA typing casework in Japan.

Base Sequence↗

Fetal and early life growth and body mass index from birth to early adulthood in 1958 British cohort: longitudinal study.

OBJECTIVES: To determine the influence of birth weight on body mass index at different stages of later life; whether this relation persists after accounting for potential confounding factors; and the role of indicators of fetal growth (birth weight relative to parental size) and childhood growth. DESIGN: Longitudinal study of the 1958 British birth cohort. SETTING: England, Scotland, and Wales. PARTICIPANTS: All singletons born 3-9 March 1958 (10 683 participants with data available at age 33). MAIN OUTCOME MEASURES: Body mass index at ages 7, 11, 16, 23, and 33 years. RESULTS: The relation between birth weight and body mass index was positive and weak, becoming more J shaped with increasing age. When adjustments were made for maternal weight, there was no relation between birth weight and body mass index at age 33. Indicators of poor fetal growth based on the mother's body size were not predictive, but the risk of adult obesity was higher among participants who had grown to a greater proportion of their eventual adult height by age 7. In men only, the effect of childhood growth was strongest in those with lower birth weights and, to a lesser extent, those born to lighter mothers. CONCLUSIONS: Maternal weight (or body mass index) largely explains the association between birth weight and adult body mass index, and it may be a more important risk factor for obesity in the child than birth weight. Birth weight and maternal weight seem to modify the effect of childhood linear growth on adult obesity in men. Intergenerational associations between the mother's and her offspring's body mass index seem to underlie the well documented association between birth weight and body mass index. Other measures of fetal growth are needed for a fuller understanding of the role of the intrauterine environment in the development of obesity.

Adolescent↗

Are levels of bone turnover related to lower bone mass of adolescents previously fed a macrobiotic diet?

Dutch adolescents who consumed a macrobiotic (vegan-type) diet in early life, demonstrate a lower relative bone mass than their omnivorous counterparts. We investigated whether subjects from the macrobiotic group showed signs of catching up with controls in terms of relative bone mass, reflected by higher levels of serum osteocalcin and alkaline phosphatase and lower levels of urinary cross-links. Group differences in calciotropic hormones and mineral excretion were also investigated. Bone measurements, blood, and urine samples were obtained from 69 macrobiotic (34 girls, 35 boys) and 99 control (57 girls, 42 boys) subjects, aged 9-15. Bone turnover markers and 1,25(OH)2D reached maximal levels at pubertal stages 3-4, and decreased thereafter. After adjusting for puberty, age, and lean body mass, no group differences were found in markers of bone turnover, 1,25(OH)2D, PTH, or calcium excretion, but phosphate excretion was 23% lower in macrobiotic girls. After adjustment for puberty, 1,25(OH)2D was positively related to osteocalcin. In summary, we found no evidence for group differences in bone turnover, or catch up in relative bone mass, which might be due to the fact that 60% of subjects were still in early stages of puberty.

Adolescent↗

Mitochondrial enteropathy: the primary pathology may not be within the gastrointestinal tract.

BACKGROUND: Mitochondrial DNA (mtDNA) defects are an important cause of disease. Although gastrointestinal symptoms are common in these patients, their pathogenesis remains uncertain. AIM: To investigate the role of the mtDNA defect in the production of gastrointestinal dysfunction. PATIENT: A 20 year old woman who presented at 15 years of age with recurrent vomiting and pseudo-obstruction, who did not respond to conservative management and ultimately had subtotal gastrectomy and Roux-en-y reconstruction. She subsequently presented with status epilepticus and was found to have a mitochondrial respiratory chain disorder due to a pathogenic mtDNA point mutation (A3243G). METHODS: Resected bowel was studied using light and electron microscopy and mtDNA analysed from both mucosal and muscular layers using polymerase chain reaction generated RFLP analysis. RESULTS: Histological and electron microscopic studies revealed no morphological abnormalities in the resected stomach, and molecular genetic analysis failed to identify the genetic defect in either the mucosal or muscle layers. CONCLUSION: This study suggests that in some individuals with gastrointestinal symptoms associated with established mitochondrial DNA disease, the primary pathology of the mitochondrial enteropathy lies outside the gastrointestinal tract.

Adolescent↗

Improved MtDNA sequence analysis of forensic remains using a "mini-primer set" amplification strategy.

Mitochondrial DNA (mtDNA) analysis of highly degraded skeletal remains is often used for forensic identification due largely to the high genome copy number per cell. Literature from the "ancient DNA" field has shown that highly degraded samples contain populations of intact DNA molecules that are severely restricted in size (1-4). Hand et al. have demonstrated the targeting and preferential amplification of authentic human DNA sequences with small amplicon products of 150 bp or less (1,2). Given this understanding of ancient DNA preservation and amplification, we report an improved approach to forensic mtDNA analysis of hypervariable regions 1 and 2 (HV1/HV2) in highly degraded specimens. This "mini-primer set" (MPS) amplification strategy consists of four overlapping products that span each of the HV regions and range from 126 to 170 bp, with an average size of 141 bp. For this study, 11 extracts representing a range of sample quality were prepared from nonprobative forensic specimens. We demonstrate a significant increase in MPS amplification success when compared to testing methods using approximately 250 bp amplicons. Further, 16 of 17 independent amplifications previously "unreported" due to mixed sequences provided potentially reportable sequence data from a single, authentic template with MPS testing.

Bone and Bones↗

Increasing the forensic discrimination of mitochondrial DNA testing through analysis of the entire mitochondrial DNA genome.

The principal limitation in forensic mitochondrial DNA (mtDNA) testing is the low power of discrimination that is obtained when common "mtDNA types" are involved in a case. Currently, an "mtDNA type" refers to the sequence within hypervariable regions I and II (HV1/HV2) of the control region, approximately 610 bp. In Caucasians, the most common HV1/HV2 type is found in approximately 7% of the population and there are 12 additional types found at greater than approximately 0.5% (ignoring HV2 C-stretch polymorphism). We are performing large scale sequencing of the entire mtDNA genome (mtGenome), approximately 16,569 bp, of individuals who have common HV1/HV2 types. Of 31 individuals with the most common HV1/HV2 type, only 3 still match after mtGenome sequencing. Similar high discrimination is seen in other common HV1/HV2 types. The sites that discriminate the various common HV1/HV2 types are generally not those that are known to vary widely in more diverse population samples. This indicates that complete mtGenome sequencing of selected HV1/HV2 types may stand as the best way for identifying maximally useful single nucleotide polymorphism sites outside of the control region. Our strategy for identifying SNP sites is useful in resolving U.S. Caucasian, Hispanic, and African American mtDNAs is discussed. We also discuss the development of homogeneous fluorogenic polymerase chain reaction assays that target phenotypically neutral sites for practical use in casework.

DNA, Mitochondrial↗

Point mutations of the mtDNA control region in normal and neurodegenerative human brains.

Recent observations in cultured human fibroblasts suggest that the accumulation of point mutations in the noncoding control region of mtDNA may be important in human aging. We studied the mtDNA control region in brain tissue from 31 normal elderly individuals, from 35 individuals who had Alzheimer disease, and from 47 individuals who had dementia with Lewy bodies. We found no evidence that these somatic mtDNA point mutations accumulate either in the brains of normal elderly individuals or in the brains of individuals with neurodegenerative disease.

Aged↗

A sensitive denaturing gradient-Gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region.

A population study of heteroplasmy in the hypervariable region 1 (HV1) portion of the human mtDNA control region was performed. Blood samples from 253 randomly chosen individuals were examined using a sensitive denaturing gradient-gel electrophoresis (DGGE) system. This method is capable of detecting heteroplasmic proportions as low as 1% and virtually all heteroplasmy where the minor component is > or = 5%. Heteroplasmy was observed in 35 individuals (13.8%; 95% confidence interval [CI] 9.6-18.0). Of these individuals, 33 were heteroplasmic at one nucleotide position, whereas 2 were heteroplasmic at two different positions (a condition known as "triplasmy"). Although heteroplasmy occurred at a total of 16 different positions throughout HV1, it was most frequently observed at positions 16093 (n=13) and 16129 (n=6). In addition, the majority of heteroplasmic variants occurred at low proportions and could not be detected by direct sequencing of PCR products. This study indicates that low-level heteroplasmy in HV1 is relatively common and that it occurs at a broad spectrum of sites. Our results corroborate those of other recent reports indicating that heteroplasmy in the control region is more common than was previously believed-a finding that is of potential importance to evolutionary studies and forensic applications that are based on mtDNA variation.

Base Sequence↗

Utility of the mitochondrial cytochrome oxidase II gene for resolving relationships among black flies (Diptera: simuliidae).

The complete mitochondrial cytochrome oxidase II gene was sequenced from 17 black flies, representing 13 putative species, and used to infer phylogenetic relationships. A midge (Paratanytarsus sp.) and three mosquitoes (Aedes aegypti, Anopheles quadrimaculatus, and Culex quinquefasciatus) were used as outgroup taxa. All outgroup taxa were highly divergent from black flies. Phylogenetic trees based on weighted parsimony (a priori and a posteriori), maximum likelihood, and neighbor-joining (log-determinant distances) differed topologically, with deeper nodes being the least well-supported. All analyses supported current classification into species groups but relationships among those groups were poorly resolved. The majority of phylogenetic signal came from closely related sister taxa. The CO-II gene may be useful for exploring relationships at or below the subgeneric level, but is of questionable value at higher taxonomic levels. The weighting method employed gave phylogenetic results similar to those reported by other authors for other insect CO-II data sets. A best estimate of phylogenetic relationships based on the CO-II gene is presented and discussed in relation to current black fly classification.

Amino Acid Sequence↗

Expression, purification and crystallization of a BH domain from the GTPase regulatory protein associated with focal adhesion kinase.

Signaling by small GTPases is down-regulated by GTPase activating proteins (GAPs) which enhance the rate of GTP hydrolysis. The activity of GAPs specific for Rho GTPases resides in the BH domain, many homologues of which are found in any mammalian genome. One of them was identified in the GTPase regulator associated with focal-adhesion kinase (GRAF). It shares approximately 20% sequence identity with p50RhoGAP. This GAP activates RhoA and Cdc42Hs, but not Rac. In order to dissect the molecular basis of this specificity, a 231-residue-long fragment corresponding to the BH domain of GRAF has been expressed, purified and crystallized. Trigonal crystals, of space group P3(1)21 or P3(2)21, with unit-cell dimensions a = b = 63.5, c = 90.38 A were grown from solutions of PEG 6000. Data to 2.15 A were collected from a flash-frozen sample on an R-AXIS IV imaging-plate detector mounted on a rotating anode X-ray generator.

Amino Acid Sequence↗

Childhood predictors of adult obesity: a systematic review.

OBJECTIVE: To identify factors in childhood which might influence the development of obesity in adulthood. BACKGROUND: The prevalence of obesity is increasing in the UK and other developed countries, in adults and children. The adverse health consequences of adult obesity are well documented, but are less certain for childhood obesity. An association between fatness in adolescence and undesirable socio-economic consequences, such as lower educational attainment and income, has been observed, particularly for women. Childhood factors implicated in the development of adult obesity therefore have far-reaching implications for costs to the health-services and economy. SEARCH STRATEGY: In order to identify relevant studies, electronic databases--Medline, Embase, CAB abstracts, Psyclit and Sport Discus-were searched from the start date of the database to Spring 1998. The general search structure for electronic databases was (childhood or synonyms) AND (fatness or synonyms) AND (longitudinal or synonyms). Further studies were identified by citations in retrieved papers and by consultation with experts. INCLUSION CRITERIA: Longitudinal observational studies of healthy children which included measurement of a risk factor in childhood (<18 y), and outcome measure at least 1 y later. Any measure of fatness, leanness or change in fatness or leanness was accepted. Measures of fat distribution were not included. Only studies with participants from an industrialized country were considered, and those concerning minority or special groups, e.g. Pima Indians or children born preterm, were excluded. FINDINGS: Risk factors for obesity included parental fatness, social factors, birth weight, timing or rate of maturation, physical activity, dietary factors and other behavioural or psychological factors. Offspring of obese parent(s) were consistently seen to be at increased risk of fatness, although few studies have looked at this relationship over longer periods of childhood and into adulthood. The relative contributions of genes and inherited lifestyle factors to the parent-child fatness association remain largely unknown. No clear relationship is reported between socio-economic status (SES) in early life and childhood fatness. However, a strong consistent relationship is observed between low SES in early life and increased fatness in adulthood. Studies investigating SES were generally large but very few considered confounding by parental fatness. Women who change social class (social mobility) show the prevalence of obesity of the class they join, an association which is not present in men. The influence of other social factors such as family size, number of parents at home and childcare have been little researched. There is good evidence from large and reasonably long-term studies for an apparently clear relationship for increased fatness with higher birth weight, but in studies which attempted to address potential confounding by gestational age, parental fatness, or social group, the relationship was less consistent. The relationship between earlier maturation and greater subsequent fatness was investigated in predominantly smaller, but also a few large studies. Again, this relationship appeared to be consistent, but in general, the studies had not investigated whether there was confounding by other factors, including parental fatness, SES, earlier fatness in childhood, or dietary or activity behaviours. Studies investigating the role of diet or activity were generally small, and included diverse methods of risk factor measurement. There was almost no evidence for an influence of activity in infancy on later fatness, and inconsistent but suggestive evidence for a protective effect of activity in childhood on later fatness. No clear evidence for an effect of infant feeding on later fatness emerged, but follow-up to adulthood was rare, with only one study measuring fatness after 7y. Studies investigating diet in childhood were limited and inconc

Adult↗

Molecular cloning, sequencing, and phylogenetic relationships of a new potyvirus: sugarcane streak mosaic virus, and a reevaluation of the classification of the potyviridae.

The nucleic acid of a serologically distinct potyvirus, originally isolated out of sugar cane from Pakistan, was reverse transcribed and the 3' terminal 2000 bp was PCR amplified, cloned, and sequenced. Phylogenetic comparisons of viruses representing each genus of the Potyviridae show that the Pakistani isolate is most closely related to the rymoviruses wheat streak mosaic virus (WSMV) and brome streak mosaic virus. We therefore propose that this new virus species be named sugar cane streak mosaic virus to reflect its similarity to WSMV. The phylogenetic data also show that the genus Rymovirus contains at least two unique evolutionary lineages. Thus the current taxonomy, based on transmission vector, is paraphyletic. We present an analysis of the taxonomic relationships among members of the family and propose a classification that both resolves the paraphyly and more accurately represents the evolutionary history of the Potyviridae.

Amino Acid Sequence↗