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Biomedical subjects

K R Fox

Publications and source records attributed to K R Fox.

At least 37 records · Page 2Linked to original sources
PubMed2000

Small-cell variant of synovial sarcoma: fine-needle aspiration with ancillary features and potential diagnostic pitfalls.

We report a small-cell variant of synovial sarcoma examined by fine-needle aspiration (FNA) biopsy. The patient is a 23-yr-old female who had a synovial sarcoma involving the left infratemporal region, diagnosed at 7 yr of age, followed by a metastatic lesion involving the lung and chest wall 16 yr later. The chest wall metastases was sampled by FNA biopsy. The aspirate consisted of numerous, small, round cells with very high nuclear-to-cytoplasmic ratios. The cytomorphologic features could potentially be confused with other pediatric small round cell tumors. Ancillary studies demonstrated positive staining of the neoplastic cells for cytokeratin, epithelial membrane antigen (EMA), and CD99. The differential diagnosis of other small round cell tumors that may be mistaken for the small-cell variant of synovial sarcoma are presented. We believe that this is the first FNA report detailing the cytologic and ancillary features of the small-cell variant of synovial sarcoma.

Adult↗
PubMed2000

Charting the physical activity patterns of contemporary children and adolescents.

The impact of physical inactivity on health is well accepted throughout the medical and health service community. However, the case has largely been established through epidemiological studies with adults. Substantial attention has been paid to the activity levels of children and adolescents, largely because of changing lifestyles that have threatened the opportunity to be active and also introduced attractive sedentary alternatives such as playing computer games. The research evidence that children have become less active to the point where it is seriously damaging their current and future health has been difficult to establish. This situation is due to difficulties in establishing sensitive health risk markers, and also with the assessment of the different elements of physical activity which in children and adolescents is a complex profile of social behaviours. Self report of activity is unreliable with young children, and objective measures are required that are cheap and effective with large samples and that are capable of measuring levels, volume and patterns of physical activity. Accelerometry in combination with diaries offers the best current solution for most activity-health relationships, and for informing intervention need and design.

Adolescent↗
PubMed2000

Physical activity patterns in normal, overweight and obese individuals using minute-by-minute accelerometry.

OBJECTIVE: To determine the levels and patterns of daily physical activity in groups of normal-weight, overweight and obese adults using uniaxial minute-by-minute accelerometry. DESIGN: Cross-sectional study of physical activity levels over a 7 day period using accelerometers programmed to collect minute-by-minute data. SETTING: Participants were recruited from large companies in Bristol and Cardiff. All meetings took place on company premises. PARTICIPANTS: One-hundred and eight participants volunteered for the study. Eighty-four (36 males, 48 females; 38.6+/-9.3 y) (mean+/-s.d. ) met the inclusion criteria for accelerometer measurements and were included in analyses. RESULTS: No significant differences in physical activity were identified between normal-weight (BMI<25) and overweight (BMI 25-29.9) participants. Obese participants (BMI>30) were significantly less active than non-obese participants (BMI< or =30) during weekdays (279.1+/-77.5 vs. 391.3+/-139.4 counts min(-1); P<0.001), weekends (222.3+/-93.9 vs. 386.2+/-177.5 counts min(-1); P<0.001) and evenings (221.1+/-126.3 vs. 380.8+/-220.7 counts min(-1); P=0.002), but not at work (307.5+/-87.2 vs 398.7+/-163.3 counts min(-1); P=0.06). Differences in activity levels between obese and non-obese participants were greater in males than females. Hour-by-hour physical activity patterns demonstrated that obese participants were less active than the non-obese for almost every hour of the weekdays and the weekend. CONCLUSIONS: Although no differences in activity emerged between overweight and normal-weight individuals, obese participants were substantially less active than the non-obese, particularly when there was a free choice of activity or no activity. The difference in activity levels was particularly pronounced in males, and unless obese individuals are compensating by lower energy intake, these activity patterns will contribute to the maintenance of or increase in the degree of obesity. Minute-by-minute accelerometry is a valuable tool for the assessment of activity patterns and may be useful to highlight periods of inactivity for intervention design.

Adult↗
PubMed2000

Assessment of abdominal fat development in young adolescents using magnetic resonance imaging.

OBJECTIVE: To determine the patterns of change and the best anthropometric indicators of intra-abdominal fat deposition in young adolescents from ages 11-13 y. SUBJECTS: Subjects were 25 boys (mean age 13.7 +/- 0.32 y) and 17 girls (mean age of 13.7 +/- 0.23 y) who had taken part in a similar study 2 y earlier at ages 11.5 +/- 0.33 y and 11.5 +/- 0.27 y, respectively. METHODS: Intra-abdominal (IA) and subcutaneous adipose (SA) tissue areas and IA/SA ratio were determined through four tranverse magnetic resonance imaging scans on two occasions. Differences were investigated using t-tests and ANOVA. Skinfolds, girths and circumferences, body mass index and hydrostatic weighing were also recorded. Pearson correlation coefficients and regression equations were calculated to determine the best anthropometric indicators of intra-abdominal fat deposition. RESULTS: Intra-abdominal fat and subcutaneous fat areas had significantly increased in boys and girls by the second measure. Boys had deposited greater amounts of fat in intra-abdominal depots so that their intra-abdominal/subcutaneous ratio had increased significantly from 0.31 to 0.39. This had reduced in girls from 0.39 to 0.35. However, patterns of change were variable within sexes. Truncal skinfold sites (r = 0.54-0.70) emerged as the best field indicators of intra-abdominal fat deposition. CONCLUSIONS: Patterns of intra-abdominal and subcutaneous fat distribution are identifiable in pubescent children using magnetic resonance imaging. An acceptable indication is provided by truncal skinfolds.

Abdomen↗
PubMed2000

Targeting DNA with triplexes.

The formation of intermolecular DNA triple helices offers the possibility of designing compounds with extensive sequence recognition properties which may be useful as antigene agents or tools in molecular biology. In these structures a third strand oligonucleotide binds in the DNA major groove, making specific contacts with substituents on the exposed faces of the base pairs. Although triplexes form with exquisite specificity their use suffers from several drawbacks. Two limitations of this approach, which are considered in this review are, firstly that conditions of low pH are necessary for formation of the C+*GC triplet, and secondly that these structures are often less stable than their duplex counterparts. This review outlines the strategies that have been employed to overcome these drawbacks. The pH problem is addressed by considering the various DNA base analogues that have been used to recognise GC base pairs in a pH independent fashion, and discusses the benefits and limitations of each analogue. Triplex stability can be increased by using novel base analogues, backbone modifications and the use of triplex-specific binding ligands.

Animals↗
PubMed1999

DNA triple helix stabilisation by covalent attachment of a triplex-specific ligand.

We have prepared oligonucleotides with a naphthylquinoline triplex-binding ligand covalently tethered to the 5'-end and have used UV-melting and DNase I footprinting to examine the stability of intra- and inter-molecular triplexes containing this modification. We find that covalent attachment of the ligand increases the melting temperature of intramolecular 6-mer triplexes by about 14 K, and increases the binding of 9-mer oligonucleotides to their duplex target sites by about 60-fold.

Animals↗
PubMed1999

DNA triple helix formation at target sites containing several pyrimidine interruptions: stabilization by protonated cytosine or 5-(1-propargylamino)dU.

DNase I footprinting has been used to study the formation of parallel triplexes at oligopurine target sequences which are interrupted by pyrimidines at regular intervals. TA interruptions are targeted with third strand oligonucleotides containing guanine, generating G x TA triplets, while CG base pairs are targeted with thymine, forming T x CG triplets. We have attempted to optimize the stability of these complexes by varying the base composition and sequence arrangement of the target sites, and by replacing the third strand thymines with the positively charged analogue 5-(1-propargylamino)dU (U(P)). For the target sequence (AAAT)(5)AA, in which pyrimidines are positioned at every fourth residue, triplex formation with TG-containing oligonucleotides is only detected in the presence of a triplex-binding ligand, though stable triplexes were detected at the target site (AAAAAT)(3)AAAA. Triplex stability at targets containing pyrimidines at every fourth residue is increased by introducing guanines into the duplex repeat unit using the targets (AGAT)(5)AA and (ATGA)(5)AA. In contrast, placing C(+) x GC triplets on the 5'-side of G x TA, using the target (AGTA)(5)TT, produces complexes of lower stability. We have attempted further to increase the stability of these complexes by using the positively charged thymine base analogue U(P), and have shown that (TU(P)TG)(5)TT forms a more stable complex with target (AAAT)(5)AA than the unmodified third strand, generating a footprint in the absence of a triplex-binding ligand. Triplex formation at (AGTA)(5)AA is improved by using the modified oligonucleotide (TCGU(P))(5)TT, generating a complex in which the charged triplets C(+) x GC and U(P) x AT alternate with uncharged triplets. In contrast, placing U(P) x AT triplets adjacent to C(+) x GC, using the third strand oligonucleotide (U(P)CGT)(5)TT, reduces triplex formation, while the third strand with both substitutions, (U(P)CGU(P))(5)TT, produces a complex with intermediate stability. It appears that, although adjacent U(P) x AT triplets form stable triplexes, placing U(P) x AT adjacent to C(+) x GC is unfavorable. Similar results were obtained with fragments containing CG inversions within the oligopurine tract, though triplexes at (AAAAAC)(3)AA were only detected in the presence of a triplex-binding ligand. Placing C(+) x GC on the 5'-side of T x CG triplets also reduces triplex formation, while a 3'-C(+) x GC produces complexes with increased stability.

Adenine↗
PubMed1999

5-(1-propargylamino)-2'-deoxyuridine (UP): a novel thymidine analogue for generating DNA triplexes with increased stability.

We have used quantitative DNase I footprinting and UV-melting studies to examine the formation of DNA triplexes in which the third strand thymines have been replaced by 5-propargylamino-dU (UP). The intra-molecular triplex A6-L-T6-L-(UP)5T (L = two octanediol residues) shows a single UV-melting transition which is >20 degrees higher than that of the parent triplex A6-L-T6-L-T6at pH 5.5. Although a single transition is observed at all pHs, the melting temperature (Tm) of the modified oligonucleotide decreases at higher pHs, consistent with the requirement for protonation of the amino group. A similar intramolecular triplex with a longer overhanging duplex shows two melting transitions, the lower of which is stabilised by substitution of T by UP, in a pH dependent fashion. Triplex stability increases by approximately 12 K for each T to UP substitution. Quantitative footprinting studies have examined the interaction of three UP-containing 9mer oligonucleotides with the different portions of the 17mer sequence 5'-AGGAAGAGAAAAAAGAA. At pH 5.0, the UP-containing oligo-nucleotides footprint to much lower concentrations than their T-containing counterparts. In particular (UP)6CUPT binds approximately 1000-fold more tightly than the unmodified oligonucleotide T6CTT. Oligonucleotides containing fewer UP residues are stabilised to a lesser extent. The affinity of these modified third strands decreases at higher pHs. These results demonstrate that the stability of DNA triplexes can be dramatically increased by using positively charged analogues of thymine.

DNA↗
PubMed1999

Towards mixed sequence recognition by triple helix formation.

The formation of intermolecular DNA triple helices offers the possibility of designing compounds with extensive sequence recognition properties which may be useful as antigene agents or tools in molecular biology. One major limitation of this approach is that these structures are generally restricted to homo-purine. homopyrimidine target sites. This review describes the strategies that have been employed to overcome this drawback and outlines the potential for triplex formation at mixed sequence DNA targets.

Binding Sites↗
PubMed1999

DNA triple helix stabilisation by a naphthylquinoline dimer.

We have used DNase I footprinting to examine the effect of a novel naphthylquinoline dimer, designed as a triplex-specific bis-intercalator, on the stability of intermolecular DNA triplexes. We find that this compound efficiently promotes triplex formation between the 9-mer oligonucleotide 5'-TTTTTTCTT and its oligopurine duplex target at concentrations as low as 0.1 microM, enhancing the triplex stability by at least 1000-fold. This compound, which is the first reported example of a triplex bis-intercalator, is about 30 times more potent than the simple monofunctional ligand.

Base Sequence↗
PubMed1999

The influence of physical activity on mental well-being.

OBJECTIVE: The case for exercise and health has primarily been made on its impact on diseases such coronary heart disease, obesity and diabetes. However, there is a very high cost attributed to mental disorders and illness and in the last 15 years there has been increasing research into the role of exercise a) in the treatment of mental health, and b) in improving mental well-being in the general population. There are now several hundred studies and over 30 narrative or meta-analytic reviews of research in this field. These have summarised the potential for exercise as a therapy for clinical or subclinical depression or anxiety, and the use of physical activity as a means of upgrading life quality through enhanced self-esteem, improved mood states, reduced state and trait anxiety, resilience to stress, or improved sleep. The purpose of this paper is to a) provide an updated view of this literature within the context of public health promotion and b) investigate evidence for physical activity and dietary interactions affecting mental well-being. DESIGN: Narrative review and summary. CONCLUSIONS: Sufficient evidence now exists for the effectiveness of exercise in the treatment of clinical depression. Additionally, exercise has a moderate reducing effect on state and trait anxiety and can improve physical self-perceptions and in some cases global self-esteem. Also there is now good evidence that aerobic and resistance exercise enhances mood states, and weaker evidence that exercise can improve cognitive function (primarily assessed by reaction time) in older adults. Conversely, there is little evidence to suggest that exercise addiction is identifiable in no more than a very small percentage of exercisers. Together, this body of research suggests that moderate regular exercise should be considered as a viable means of treating depression and anxiety and improving mental well-being in the general public.

Depression↗
PubMed1999

Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: impact on the delivery of local-regional radiation therapy.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. PATIENTS AND METHODS: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. RESULTS: Overall and disease-free survival rates at 18 months were 83% (+/- 4%) and 77% (+/- 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%-80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%-24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. CONCLUSION: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.

Adult↗
PubMed1999

DNA triple-helix formation on nucleosome core particles. Effect of length of the oligopurine tract.

We have used DNase I footprinting to examine the formation of intermolecular triplexes on DNA fragments which have been complexed with nucleosome core particles. We have prepared five DNA fragments, based on the 160-bp tyrT sequence, which contain different length oligopurine tracts (up to 25 bp) at two different positions along the fragment, and have examined their availability for triple-helix formation after reconstituting onto nucleosome core particles. These results are compared with the formation of shorter triplexes in the same regions. In general we find that increasing the length of the complex does not facilitate nucleosomal triplex formation and that the most important factor affecting triplex formation is the position of the target site within the nucleosome-bound fragment. In some instances we find that longer oligonucleotides inhibit triplex formation. Although successful triplex formation was achieved on the longest nucleosome-bound oligopurine tracts, this was accompanied by changes in cleavage pattern that suggest oligonucleotide-induced changes in nucleosome structure.

Animals↗
PubMed1999

Stabilization of DNA triple helices by a series of mono- and disubstituted amidoanthraquinones.

We have used quantitative DNase I footprinting to measure the relative affinities of four disubstituted and two monosubstituted amidoanthraquinone compounds for intermolecular DNA triplexes, and have examined how the position of the attached base-functionalized substituents affects their ability to stabilize DNA triplexes. All four isomeric disubstituted derivatives examined stabilize DNA triplexes at micromolar or lower concentrations. Of the compounds studied the 2,7-disubstituted amidoanthraquinone displayed the greatest triplex affinity. The order of triplex affinity for the other disubstituted ligands decreases in the order 2,7 > 1,8 = 1,5 > 2,6, with the equivalent monosubstituted compounds being at least an order of magnitude less efficient. The 1,5-disubstituted derivative also shows some interaction with duplex DNA. These results have been confirmed by molecular modelling studies, which provide a rational basis for the structure-activity relationships. These suggest that, although all of the compounds bind through an intercalative mode, the 2,6, 2,7 and 1,5 disubstituted isomers bind with their two side groups occupying adjacent triplex grooves, in contrast with the 1,8 isomer which is positioned with both side groups in the same triplex groove.

Amides↗
PubMed1999

Achievement goals, beliefs about the causes of success and reported emotion in post-16 physical education.

The main aim of this study was to examine whether goal orientations of male and female adolescents involved in an optional post-16 physical education (PE) programme were related in a conceptually consistent manner with their beliefs about the causes of success in PE. We also determined relationships between these achievement goal-belief dimensions and reported enjoyment and boredom within PE classes. Participants (n = 171) in a sixth-form college PE programme completed an inventory assessing their task and ego goal orientations, beliefs about the determinants of success in PE, and emotion in PE activities at college. Separate factor analyses of goal orientations and beliefs for male and female students revealed two goal-belief dimensions. The first dimension showed ego orientation was linked to the view that ability and deceptive tactics lead to success. The second dimension suggested task orientation was associated with the belief that success is the result of hard work and effort. This task goal-belief factor was found to be more strongly correlated with enjoyment in PE among female students than among males. For boys, the task goal-belief factor was correlated significantly and negatively with boredom in PE, but this was not the case for girls. No significant relationships emerged between the ego goal-belief factor and reported emotion in PE among the male and female participants. Facilitating task involvement and beliefs about causes of success that are fundamentally under personal control may, therefore, promote positive affective experiences in sixth-form PE, especially among female students.

Achievement↗
PubMed1999

Cost-effectiveness of MR imaging and core-needle biopsy in the preoperative work-up of suspicious breast lesions.

PURPOSE: To assess the clinical and economic consequences of the use of preoperative breast magnetic resonance (MR) imaging and core-needle biopsy (CNB) to avert excisional biopsy (EXB). MATERIALS AND METHODS: A decision-analytic Markov model was constructed to compare MR imaging, CNB, and EXB without preoperative testing in a woman with a suspicious breast lesion. Stage-specific cancer prevalence, tumor recurrence, progression rates, and MR imaging and CNB sensitivity and specificity were obtained from the literature. Cost estimates were obtained from the literature and from the Medicare fee schedule. RESULTS: EXB without preoperative testing was associated with the greatest quality-adjusted life expectancy, followed by MR imaging and CNB; life expectancies were 17.409, 17.405, and 17.398 years, respectively. EXB resulted in the greatest lifetime treatment cost ($31,438), followed by MR imaging ($29,072) and CNB ($28,573). Results were robust over a wide range of cancer prevalence, stage distribution, tumor progression rates, and procedure and treatment costs. Incremental cost-effectiveness ratios showed that preoperative testing was cost-effective, but the choice between MR imaging and CNB was highly dependent on the accuracy of each test and to patient preferences. CONCLUSION: Preoperative testing of most suspicious breast lesions was cost-effective. More precise estimates of MR imaging and CNB test performance characteristics are needed. Until those are available, patient preferences should inform individual decisions regarding preoperative testing.

Biopsy, Needle↗