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Biomedical subjects

C A Powell

Publications and source records attributed to C A Powell.

At least 19 recordsLinked to original sources
PubMed2006

Molecular profiling of malignant peritoneal mesothelioma identifies the ubiquitin-proteasome pathway as a therapeutic target in poor prognosis tumors.

Malignant mesothelioma is an aggressive neoplastic proliferation derived from cells lining serosal membranes. The biological and clinical characteristics of epithelial type malignant mesothelioma are distinct from those of biphasic and sarcomatous type tumors. The goal of our study was to examine the molecular basis for this distinction. Microarray analysis confirmed that the molecular signatures of epithelial and biphasic histologic subtypes were distinct. Among the differentially expressed functional gene categories was the ubiquitin-proteasome pathway, which was upregulated in biphasic tumors. Cytotoxicity experiments indicated that 211H cells derived from biphasic tumors were synergistically sensitive to sequential combination regimens containing the proteasome inhibitor bortezomib and oxaliplatin. The mechanism of this synergistic response, which was not detected in cells of epithelial tumor origin, was apoptosis. Together, our results identify the ubiquitin-proteasome pathway as a biomarker of poor prognosis biphasic peritoneal mesothelioma tumors and suggest that proteasome inhibitors could increase the effectiveness of cytotoxic chemotherapy in this subset of patients.

Adult↗
PubMed2006

The association between early childhood stunting and weight status in late adolescence.

BACKGROUND: Cross-sectional studies have shown associations between stunting and overweight; however, there are few prospective studies of stunted children. OBJECTIVES: To determine whether stunting before age 2 years is associated with overweight and central adiposity at 17-18 years and whether growth in height among stunted children predicts body mass index (BMI) in late adolescence. DESIGN: Prospective cohort study. PARTICIPANTS: One-hundred and three participants stunted by age 2 years and 64 non-stunted participants (78% of participants enrolled in childhood). Participants were measured in early childhood and at ages 7, 11 and 17 years. RESULTS: Stunted subjects remained shorter and had lower BMIs, smaller skinfolds and circumferences than non-stunted subjects. Overweight (BMI >/=25 m(2)) was not significantly different among stunted and non-stunted male subjects (5.2 and 12.5%) but non-stunted female subjects were more likely to be overweight than those who experienced early childhood stunting (11.1 and 34.4%, P=0.013). Centralization of fat (waist to hip ratio (WHR), subscapular/triceps skinfold ratio (SSF/TSF)) did not differ between stunted and non-stunted groups (mean WHR 0.77 and mean SSF/TSF 1.18 in both groups). Stunted subjects with greater increases in height-for-age for the intervals 3-7 and 7-11 years had higher BMI at age 17 years (P=0.04 and P=0.001, respectively). CONCLUSION: Participants stunted by age 2 years were less likely to be overweight than those who were never stunted. This suggests that cross-sectional studies of the association between stunting and overweight may be misleading. Among stunted children, greater linear growth during mid- to late childhood was associated with greater BMI at age 17 years.

Adiposity↗
PubMed2003

Factors associated with size and proportionality at birth in term Jamaican infants.

The objective of this study was to identify the factors associated with size and proportionality at birth in a cohort of term infants established to investigate their growth and development. One hundred and forty term low-birth-weight (birth-weight < 2,500 g) infants and 94 normal birth-weight infants (2,500- < 4,000 g) were recruited within 48 hours of birth at the main maternity hospital, Kingston, Jamaica. Birth anthropometry and gestational age were measured, and maternal information was obtained by interview and from hospital records. Controlling for gestational age, variables independently associated with birth-weight were rate of weight gain in the second half of pregnancy, maternal height, haemoglobin level < 9.5 microg/dL, time of first attendance in antenatal clinic, birth order, pre-eclampsia, and consumption of alcohol, with 33% of the variance in birth-weight explained. Birth length was associated only with maternal height and age, while measures of proportionality (ponderal index and head/length ratio) were associated with characteristics of the environment in late pregnancy, including rate of weight gain, weight in late pregnancy, and pre-eclampsia. The variation in maternal characteristics associated with size or proportionality at birth may reflect the times during gestation when different aspects of growth are most affected.

Adult↗
PubMed2002

Fasting levels of serum glucose, cholesterol and triglyceride at age eleven to twelve years in stunted and non-stunted Jamaican children.

AIM: To determine whether fasting serum concentrations of glucose, cholesterol and triglyceride at age 11-12 y (a) differed between children stunted in early childhood and those who were never stunted, (b) were related to birthweight or current anthropometry and (c) were related to stunting after controlling for current size. METHODS: Anthropometry, serum glucose and lipid concentrations were measured in 112 children stunted in early childhood and 181 non-stunted children. RESULTS: Children who were stunted in infancy remained shorter, weighed less and were significantly less fat than non-stunted children but had a more central distribution of fat. They were also less likely to have entered puberty. Non-stunted children had higher fasting serum triglyceride concentrations than stunted children (p < 0.05). There were no significant correlations between birthweight and fasting glucose or any measure of serum lipids. The percentage of variance in biochemical measures explained by anthropometry was low: between 2.1 for HDL cholesterol and 14.6 for triglyceride. Nutritional status in early childhood (stunted or non-stunted) made no additional contribution to the variance. CONCLUSIONS: Linear growth retardation in early childhood was not independently related to fasting serum concentrations of glucose, cholesterol and triglyceride at age 11-12 y. However, despite being thinner, stunted children had a more central distribution of fat.

Analysis of Variance↗
PubMed2002

Early childhood stunting and later behaviour and school achievement.

BACKGROUND: Stunting in early childhood is common in developing countries and is associated with poorer cognition and school achievement in later childhood. The effect of stunting on children's behaviours is not as well established and is examined here. METHOD: Children who were stunted at age 9 to 24 months and had taken part in a 2-year intervention programme of psychosocial stimulation with or without nutritional supplementation were reexamined at age 11-12 years and compared with non-stunted children from the same neighbourhoods. Their school and home behaviours were assessed using the Rutter Teacher and Parent Scales and school achievement was measured using the Wide Range Achievement Test (WRAT) and the Suffolk Reading Scales. RESULTS: No significant intervention effects were found among the stunted groups. Thus data from the four intervention groups were aggregated for subsequent analyses, comparing all 116 stunted children with 80 non-stunted children. Controlling for social background variables, the stunted group had more conduct difficulties (p < .05) as rated by their parents. They also had significantly lower scores in arithmetic, spelling, word reading and reading comprehension than the non-stunted children (all p < .001). Conduct difficulties and hyperactivity were related to poorer school achievement. Controlling for the children's IQ, the stunted children's arithmetic scores remained significantly lower than those of the non-stunted children, but reading and spelling scores were not different. CONCLUSIONS: Previously stunted children had more conduct difficulties at home, regardless of their social background, than non-stunted children. Their educational attainment was also poorer than non-stunted children and these results are suggestive of a specific arithmetic difficulty. Children with behaviour problems performed less well at school.

Achievement↗
PubMed2001

Pulmonary function tests in preoperative pulmonary evaluation.

Pulmonary function testing (PFT) is used extensively by pulmonary specialists to address two common clinical questions: (1) What is the risk of a postoperative pulmonary complication in an individual with lung disease? and (2) Will the patient be able to tolerate lung resection surgery? Today, there are numerous tests available to measure pulmonary function; making judicious use of these tests essential. In this article, the authors describe significant postoperative pulmonary complications, and discuss the surgical and patient factors contributing to the risk of these complications. They provide an evidence-based approach using pulmonary function data to determine an individual patient's risk for pulmonary complications associated with three types of surgical procedures-upper abdominal, cardiac, and lung resection-and discuss recommendations for risk education.

Heart Diseases↗
PubMed2001

The effects of birth weight and postnatal linear growth retardation on blood pressure at age 11-12 years.

STUDY OBJECTIVE: To determine the effects of birth weight and linear growth retardation (stunting) in early childhood on blood pressure at age 11-12 years. DESIGN: Prospective cohort study. SETTING: Kingston, Jamaica. PARTICIPANTS: 112 stunted children (height for age < -2 SD of the NCHS references) and 189 non-stunted children (height for age > -1 SD), identified at age 9-24 months by a survey of poor neighbourhoods in Kingston. MAIN RESULTS: Current weight was the strongest predictor of systolic blood pressure (beta= 4.90 mm Hg/SD weight 95%CI 3.97, 5.83). Birth weight predicted systolic blood pressure (beta = -1.28 mm Hg/SD change in birth weight, 95% CI -2.17, -0.38) after adjustment for current weight. There was a significant negative interaction between stunting in early childhood and current weight indicating a larger effect of increased current weight in children who experienced linear growth retardation in early childhood. There was no interaction between birth weight and current weight. The increase in blood pressure from age 7 to age 11-12 was greater in children with higher weight at age 11-12 and less in children with higher birth weight and weight at age 7. CONCLUSIONS: Birth weight predicted systolic blood pressure in Jamaican children aged 11-12. Postnatal growth retardation may potentiate the relation between current weight and blood pressure. Greater weight gain between ages 7 and 11 was associated with a greater increase in systolic blood pressure. The relation between growth and later blood pressure is complex and has prenatal and postnatal components.

Anthropometry↗
PubMed2000

Effects of growth restriction in early childhood on growth, IQ, and cognition at age 11 to 12 years and the benefits of nutritional supplementation and psychosocial stimulation.

OBJECTIVES: (1) To determine whether benefits to growth and cognition remain after intervention in growth-restricted children who received psychosocial stimulation and nutritional supplementation in early childhood. (2) To investigate the extent of the differences in IQ and cognition at age 11 to 12 years between growth-restricted and non-growth-restricted children. STUDY DESIGN: Growth-restricted and non-growth-restricted children were identified at age 9 to 24 months, at which time the growth-restricted children participated in a 2-year randomized trial of nutritional supplementation and psychosocial stimulation. Eight years after the interventions ended, the children's growth, IQ, and cognitive functions were measured. RESULTS: There were no significant benefits from supplementation to growth or cognition. Children who had received stimulation had higher scores on the Weschler Intelligence Scales for Children-Revised full-scale (IQ) and verbal scale and tests of vocabulary and reasoning (all P <.05). The growth-restricted children had significantly lower scores than the non-growth-restricted children on 10 of 11 cognitive tests. CONCLUSIONS: Psychosocial stimulation had small but significant long-term benefits on cognition in growth-restricted children. Growth-restricted children had significantly poorer performance than non-growth-restricted children on a wide range of cognitive tests, supporting the conclusion that growth restriction has long-term functional consequences.

Child↗
PubMed2000

Homocysteine-induced inhibition of endothelium-dependent relaxation in rabbit aorta: role for superoxide anions.

Hyperhomocysteinemia is associated with endothelial dysfunction, although its mechanism is unknown. Isometric tension recordings and lucigenin chemiluminescence were used to assess the effects of homocysteine exposure on endothelium-dependent and -independent relaxation in isolated rabbit aortic rings and superoxide anion (O(2)(-)) production by cultured porcine aortic endothelial cells, respectively. Homocysteine (0.1 to 10 mmol/L) produced a significant (P<0.001) concentration- and time-dependent inhibition of endothelium-dependent relaxation in response to both acetylcholine and the calcium ionophore A23187. Only the intracellular O(2)(-) scavenger 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron, 10 mmol/L) significantly (P<0.001) inhibited the effect of homocysteine on acetylcholine- and A23187-induced relaxation. Incubation of porcine aortic endothelial cells with homocysteine (0.03 to 1 mmol/L for up to 72 hours) caused a significant (P<0.001) time-dependent increase in the O(2)(-) released by these cells on the addition of Triton X-100 (1% [vol/vol]), with levels returning to values comparable to those of control cells at the 72-hour time point. These changes in O(2)(-) levels were associated with a time-dependent increase in endothelial cell superoxide dismutase activity, becoming significant (P<0.001) after 72 hours. Furthermore, the homocysteine-induced increase in endothelial cell O(2)(-) levels was completely inhibited (P<0.001) by the concomitant incubation with either Tiron (10 mmol/L), vitamin C (10 micromol/L), or vitamin E (10 micromol/L). These data suggest that the inhibitory effect of homocysteine on endothelium-dependent relaxation is due to an increase in the endothelial cell intracellular levels of O(2)(-) and provide a possible mechanism for the endothelial dysfunction associated with hyperhomocysteinemia.

Acridines↗
PubMed1999

The final step of pantothenate biosynthesis in higher plants: cloning and characterization of pantothenate synthetase from Lotus japonicus and Oryza sativum (rice).

We have isolated a Lotus japonicus cDNA for pantothenate (vitamin B(5)) synthetase (PS) by functional complementation of an Escherichia coli panC mutant (AT1371). A rice (Oryza sativum) expressed sequence tag, identified by sequence similarity to PS, was also able to complement the E. coli auxotroph, as was an open reading frame from Saccharomyces cerevisiae (baker's yeast). The Lotus and rice cDNAs encode proteins of approx. 34 kDa, which are 65% similar at the amino acid level and do not appear to encode N-terminal extensions by comparison with PS sequences from other organisms. Furthermore, analysis of genomic sequence flanking the coding sequence for PS in Lotus suggests the original cDNA is full-length. The Lotus and rice PSs are therefore likely to be cytosolic. Southern analysis of Lotus genomic DNA indicates that there is a single gene for PS. Recombinant PS from Lotus, overexpressed in E. coli AT1371, is a dimer. The enzyme requires d-pantoate, beta-alanine and ATP for activity and has a higher affinity for pantoate (K(m) 45 microM) than for beta-alanine (K(m) 990 microM). Uncompetitive substrate inhibition becomes significant at pantoate concentrations above 1 mM. The enzyme displays optimal activity at about 0.5 mM pantoate (k(cat) 0.63 s(-1)) and at pH 7.8. Neither oxopantoate nor pantoyl-lactone can replace pantoate as substrate. Antibodies raised against recombinant PS detected a band of 34 kDa in Western blots of Lotus proteins from both roots and leaves. The implications of these findings for pantothenate biosynthesis in plants are discussed.

Amino Acid Sequence↗
PubMed1999

Loss of heterozygosity in epithelial cells obtained by bronchial brushing: clinical utility in lung cancer.

To determine whether loss of heterozygosity (LOH) could be a useful diagnostic test for lung cancer, we evaluated LOH in cells obtained from bronchial brushings. Cells from radiographically normal and abnormal lungs were obtained from 55 patients undergoing diagnostic bronchoscopy. Among 38 patients with lung cancer, LOH was present in at least one chromosomal locus in 79%, whereas cytology was positive for malignant cells in 37%. LOH was not restricted to the airway containing the tumor; fifty-three percent of the cancer patients had LOH in the contralateral lung, as did 59% of patients without lung cancer. There was an association between the extent of LOH and proximity to the cancer. The LOH score, which combined measures of fractional allelic loss and percentage of cells with allelic loss, was greater in subjects with positive cytology and on the side of the tumor. A LOH score >10 was positive in 58% of tumor-bearing lungs, in 13% of the contralateral lungs in cancer patients, and in no patients without cancer. Our results suggest that extensive and widespread allelic loss, as indicated by a high LOH score, may be diagnostic of lung cancer. Additional studies will be needed to clarify the clinical potential of using bronchial epithelial cell LOH as a biomarker and diagnostic test for lung cancer.

Adult↗
PubMed1999

The nutritional status of rural Jamaican school children.

Three thousand, eight hundred and eighty-two (3,882) children in grades 2-5, attending 16 rural primary and all-age schools in central Jamaica were weighed and their weight-for-age standard deviation scores calculated using the World Health Organization/National Center for Health Statistics (WHO/NCHS) references. Heights were also measured in a random sample of the grade 5 children (n = 793) and height-for-age and body mass index (BMI-kg/m2) calculated. Sixty-nine per cent of the total sample were of normal weight-for-age, 2% were moderately undernourished (weight-for-age > -3 Z-score, < or = -2 Z-score), and a further 24% mildly undernourished (weight-for-age > -2 Z-score, < or = -1 Z-score). Few children were overweight. The frequency distribution of weight-for-age was similar in girls and boys. In the subsample of children in whom heights were measured, 25.8% were < or = -1 Z-score height-for-age, and of these 4.9% were < -2 Z-score. Compared with a survey conducted in a similar rural area in the 1960s, the children's mean weights for age group categories were 1.1 to 3.7 kg heavier. Children who were older than appropriate for their grade were more likely to be undernourished (Odds ratio 3.94, 95% CI 3.21, 4.83), which suggests that undernourished children may be more likely to repeat a grade or start school later.

Body Constitution↗
PubMed1998

Schoolchildren's diets and participation in school feeding programmes in Jamaica.

OBJECTIVES: To describe food consumption during the school day of rural Jamaican children and participation in two government school feeding programmes. To determine factors which were related to these. DESIGN: Cross sectional. SETTING: 16 primary schools in rural Jamaica. SUBJECTS: 415 children in grades 2 and 5 (ages 7 and 10 years). RESULTS: Consumption of sweets, sweet drinks and snacks was high. Mean intakes at lunch were: energy 1537 kJ (SD 756), protein 10.4 g (SD 7.6) and iron 1.5 mg (SD 1.2). The mean energy intake was 17-20% of the daily requirement for this age group. Two types of school feeding programmes were available in the schools, one provided a cooked meal and the other a bun and milk. Median availability of school meals (as a percentage of children enrolled in the schools) over three terms was 24.6% (range 0-85.4%). Twenty per cent of the children participated in one or other programme. Poorer children were more likely to participate in the bun and milk programme (odds ratio 2.1, 95% CI 1.3-3.5) but children with more money to purchase food participated in the more costly cooked meal programme (odds ratio 2.4, 95% CI 1.3-4.6). CONCLUSIONS: Energy intakes at lunch in Jamaican children were somewhat below optimal levels and the reliance on sweets and snacks is an area of concern. Programme characteristics such as meal cost, may affect access to school feeding by poor children.

Analysis of Variance↗
PubMed1998

Nutrition and education: a randomized trial of the effects of breakfast in rural primary school children.

Hunger during school may prevent children in developing countries from benefiting from education. Although many countries have implemented school feeding programs, few programs have been rigorously evaluated. We conducted a randomized, controlled trial of giving breakfast to undernourished and adequately nourished children. The undernourished group comprised 407 children in grades 2-5 in 16 rural Jamaican schools (weights-for-age < or = -1 SD of the National Center for Health Statistics references) and the adequately nourished group comprised 407 children matched for school and class (weights-for-age >-1 SD). Both groups were stratified by class and school, then randomly assigned to breakfast or control groups. After the initial measurements, breakfast was provided every school day for 1 school year. Children in the control group were given one-quarter of an orange and the same amount of attention as children in the breakfast group. All children had their heights and weights measured and were given the Wide Range Achievement Test before and after the intervention. School attendance was taken from the schools' registers. Compared with the control group, height, weight, and attendance improved significantly in the breakfast group. Both groups made poor progress in Wide Range Achievement Test scores. Younger children in the breakfast group improved in arithmetic. There was no effect of nutritional group on the response to breakfast. In conclusion, the provision of a school breakfast produced small benefits in children's nutritional status, school attendance, and achievement. Greater improvements may occur in more undernourished populations; however, the massive problem of poor achievement levels requires integrated programs including health and educational inputs as well as school meals.

Absenteeism↗
PubMed1997

Modulation of the antigenic reactivity of the citrus tristeza virus coat protein.

Trapping properties of a panel of monoclonal antibodies (Mabs) raised against citrus tristeza virus (CTV) were analyzed in an indirect double-antibody sandwich ELISA (I-DAS-ELISA). These antibodies had been previously assigned by serological specificity into five groups (I to V). Mabs from group V, which are directed to conformational epitopes, trapped significant amounts of virus antigen from CTV-infected plant tissue at IgG concentration above 10 ng/ml. Mabs from groups I to IV, which are directed to linear, continuous epitopes, performed poorly as coating antibodies, even at a 1 microgram/ml concentration of the IgG's, indicating that the respective linear epitopes were inaccessible. However, when Mabs from groups I to IV were combined with a small amount of Mabs from group V, a substantial increase in trapping of the CTV antigen was recorded. In this 'two antibody-binding assay' previously cryptic, linear epitopes of the CTV CP apparently became accessible to the Mabs from groups I to IV. Modulation of the antigenic reactivity of the CTV CP was also recorded upon binding of the Mabs directed to the conformational epitopes in solution. Induced exposure of the linear epitopes of the CTV CP was revealed in 'two antibody-binding assays' with pairwise combinations of different mouse Mabs and several rabbit and chicken polyclonal antisera with different serological specificities, including antisera to bacterially expressed CP fragments. This mixed coating in I-DAS-ELISA resulted in substantially increased efficiency of the virus antigen trapping by antisera produced against bacterially expressed protein fragments and an increased sensitivity of the CTV detection after optimization of the ratio between conformational and linear antibodies.

Antibodies, Viral↗
PubMed1997

Nutrition, anaemia, geohelminth infection and school achievement in rural Jamaican primary school children.

OBJECTIVE: To determine whether nutritional status, anaemia and geohelminth infections were related to school achievement and attendance in Jamaican children. DESIGN: A cross-sectional study using a randomly selected sample. SUBJECTS: Eight hundred children aged 9-13 y randomly selected from those enrolled in grade 5 in 16 primary schools in rural Jamaica. RESULTS: The mean height-for-age of the children was -0.37 z-score +/- 1.0 s.d. with 4.9% having heights-for-age < -2 s.d. of the NCHS references. Anaemia (Hb < 11 g/dl) was present in 14.7% of the children, 38.3% were infected with Trichuris trichiura and 19.4% with Ascaris lumbricoides. Achievement levels on the Wide Range Achievement Test were low, with children performing at grade 3 level. In multilevel analyses, controlling for socioeconomic status, children with Trichuris infections had lower achievement levels than uninfected children in spelling, reading and arithmetic (P < 0.05). Children with Ascaris infections had lower scores in spelling and reading (P < 0.05) Height-for-age (P < 0.01) was positively associated with performance in arithmetic. Ascaris infection (P < 0.001) and anaemia (P < 0.01) predicted poorer school attendance. CONCLUSION: Despite mild levels, undernutrition and geohelminth infections were associated with achievement, suggesting that efforts to increase school achievement levels in developing countries should include strategies to improve the health and nutritional status of children.

Adolescent↗