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Biomedical subjects

C White

Publications and source records attributed to C White.

At least 37 records · Page 2Linked to original sources
PubMed2001

Penetration of herbicides to groundwater in an unconfined chalk aquifer following normal soil applications.

The persistence and penetration of the herbicides isoproturon and chlorotoluron in an unconfined chalk aquifer has been monitored over a 4-year period through soil sampling, shallow coring and groundwater monitoring. Chlorotoluron was applied on plots as a marker compound, having never been used previously on that, or surrounding fields. The fieldsite had a 5 degree slope with soil depths of 0.5 to 1.5 m and a water table between 20 and 5 m from the soil surface. Where the water table was deepest (9-20 m below surface (mbs)) little or no positive herbicide detections were made. However, where the water table was at only 4-5 mbs, a regular pesticide signal of around 0.1 microg/l for isoproturon and chlorotoluron could be distinguished. Over the winter recharge period automatic borehole samplers revealed a series of short-lived peaks of isoproturon and chlorotoluron reaching up to 0.8 microg/l. This is consistent with a preferential flow mechanism operating at this particular part of the field. Such peaks were occurring over 2 years after the last application of these compounds. Shallow coring failed to uncover any significant pesticide pulse moving through the deep unsaturated zone matrix at the fieldsite.

Environmental Monitoring↗
PubMed2001

Formation of a tyrosyl radical intermediate in Proteus mirabilis catalase by directed mutagenesis and consequences for nucleotide reactivity.

Proteus mirabilis catalase (PMC) belongs to the family of NADPH binding catalases. The function of NADPH in these enzymes is still a matter of debate. This study presents the effects of two independent phenylalanine mutations (F194 and F215), located between NADPH and heme in the PMC structure. The phenylalanines were replaced with tyrosines which we predicted could carry radicals in a NADPH-heme electron transfer. The X-ray crystal structures of the two mutants indicated that neither the binding site of NADPH nor the immediate environment of the residues was affected by the mutations. Measurements using H2O2 as a substrate confirmed that the variants were as active as the native enzyme. With equivalent amounts of peroxoacetic acid, wild-type PMC, F215Y PMC, and beef liver catalase (BLC) formed a stable compound I, while the F194Y PMC variant produced a compound I which was rapidly transformed into compound II and a tyrosyl radical. EPR studies showed that this radical, generated by the oxidation of Y194, was not related to the previously observed radical in BLC, located on Y369. In the presence of excess NADPH, compound I was reduced to a resting enzyme (k(obs) = 1.7 min(-1)) in a two-electron process. This was independent of the enzyme's origin and did not require any thus far identified tyrosyl radicals. Conversely, the presence of a tyrosyl radical in F194Y PMC greatly enhanced the oxidation of reduced beta-nicotinamide mononucleotide under a steady-state H2O2 flow with observable compound II. This process could involve a one-electron reduction of compound I via Y194.

Animals↗
PubMed2001

Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin.

BACKGROUND: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. METHOD: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. RESULTS: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). CONCLUSIONS: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.

Adolescent↗
PubMed2001

c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription.

Interleukin 12 (IL-12) is a 70-kD proinflammatory cytokine produced by antigen presenting cells that is essential for the induction of T helper type 1 development. It comprises 35-kD (p35) and 40-kD (p40) polypeptides encoded by separate genes that are induced by a range of stimuli that include lipopolysaccharide (LPS), DNA, and CD40 ligand. To date, the regulation of IL-12 expression at the transcriptional level has mainly been examined in macrophages and restricted almost exclusively to the p40 gene. Here we show that in CD8(+) dendritic cells, major producers of IL-12 p70, the Rel/nuclear factor (NF)-kappaB signaling pathway is necessary for the induction of IL-12 in response to microbial stimuli. In contrast to macrophages which require c-Rel for p40 transcription, in CD8(+) dendritic cells, the induced expression of p35 rather than p40 by inactivated Staphylococcus aureus, DNA, or LPS is c-Rel dependent and regulated directly by c-Rel complexes binding to the p35 promoter. This data establishes the IL-12 p35 gene as a new target of c-Rel and shows that the regulation of IL-12 p70 expression at the transcriptional level by Rel/NF-kappaB is controlled through both the p35 and p40 genes in a cell type-specific fashion.

Animals↗
PubMed2001

Usefulness of calcium scoring using electron beam computed tomography and noninvasive coronary angiography in patients with suspected coronary artery disease.

The aim of this study was to investigate the reliability of calcium scoring (CS) and electron beam computed tomographic angiography (EBCTA) as a noninvasive tool in the diagnosis of coronary artery disease (CAD): 93 consecutive patients (aged 59 +/- 9 years) with symptoms suspicious for CAD underwent CS. In 87 of these subjects, an additional EBCTA investigation was performed. Using receiver-operating characteristic curve analysis, we determined a calcium score cut point providing an overall sensitivity of 80% and a specificity of 72% in detecting patients with CAD. For clinical purposes the use of cut points is difficult. We therefore determined score ranges providing >80% specificity (high score range) and >85% sensitivity (low score range) and determined the scores between these ranges as equivocal borderline scores. Calculated on a per-segment basis in assessable proximal and midcoronary segments, the sensitivity for detecting coronary stenoses >50% was 78%, and the specificity was 93%. Thus, 32 of 44 patients with significant CAD and 24 of 49 patients without CAD were correctly classified. The combination of CS and EBCTA predicted CAD in 77% (72 of 93) of patients. No or low calcium scores provided high specificity for ruling out CAD. The addition of EBCTA in those patients improved sensitivity. In patients with high calcium scores, accuracy of EBCTA was not significantly different from CS alone (72% vs 83%), whereas in patients with borderline scores it was significantly superior (80% vs 58%, p <0.03). Thus, the complementary use of CS and EBCTA appears beneficial, particularly in patients with borderline scores, and could improve sensitivity in the low score range. In the presence of high scores, no major diagnostic gain from an additional EBCTA versus CS alone could be observed.

Calcinosis↗
PubMed2001

Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regions.

Family and twin studies have indicated that genes influence susceptibility to panic and phobic anxiety disorders, but the location of the genes involved remains unknown. Animal models can simplify gene-mapping efforts by overcoming problems that complicate human pedigree studies including genetic heterogeneity and high phenocopy rates. Homology between rodent and human genomes can be exploited to map human genes underlying complex traits. We used regions identified by quantitative trait locus (QTL)-mapping of anxiety phenotypes in mice to guide a linkage analysis of a large multiplex pedigree (99 members, 75 genotyped) segregating panic disorder/agoraphobia. Two phenotypes were studied: panic disorder/agoraphobia and a phenotype ("D-type") designed to capture early-onset susceptibility to anxiety disorders. A total of 99 markers across 11 chromosomal regions were typed. Parametric lod score analysis provided suggestive evidence of linkage (lod = 2.38) to a locus on chromosome 10q under a dominant model with reduced penetrance for the anxiety-proneness (D-type) phenotype. Nonparametric (NPL) analysis provided evidence of linkage for panic disorder/agoraphobia to a locus on chromosome 12q13 (NPL = 4.96, P = 0.006). Modest evidence of linkage by NPL analysis was also found for the D-type phenotype to a region of chromosome 1q (peak NPL = 2.05, P = 0.035). While these linkage results are merely suggestive, this study illustrates the potential advantages of using mouse gene-mapping results and exploring alternative phenotype definitions in linkage studies of anxiety disorder.

Animals↗
PubMed2001

Differential regulation and expression of hyaluronan synthases in human articular chondrocytes, synovial cells and osteosarcoma cells.

Recently three isoforms of hyaluronan synthase (HAS), the enzyme responsible for hyaluronate/hyaluronan (HA) biosynthesis, have been cloned, allowing us to study their expression pattern. Our objective was to determine which of the HAS isoenzymes were expressed in human articular chondrocytes, synovial fibroblasts and osteosarcoma cells, whether their expression could be modulated by growth factors (insulin-like growth factor-1, basic fibroblast growth factor and transforming growth factor (TGF-beta1) and cytokines [interleukin 1beta1 (IL-1beta)], and whether changes in the rate of HA synthesis by the cells correlated with changes in mRNA levels for one or more of the HAS isoforms. All three HAS isoforms were found to be expressed in the cultured cells analysed in this study, although the relative proportions varied for each cell type. HAS2 mRNA was usually predominant in chondrocytes, whereas synovial cells contained increased amounts of HAS1. HAS3 was always the least abundant message. The rapidly growing osteosarcoma cells contained almost exclusively HAS2 message. HAS usage in uncultured cartilage and synovial tissues was similar to that in the cultured cells, with HAS2 message being the predominant species in cartilage and HAS1 usually being the predominant species in synovium. HA synthesis was stimulated by the growth factors, but the extent of the response was cell-type specific. Synovial cells responded particularly well to IL-1beta, and showed a unique synergistic response when IL-1beta was used in combination with TGF-beta1. This response was much reduced in articular chondrocytes and absent in the osteosarcoma cells. Analysis of changes in HAS message levels indicated that there was often no correlation with the changes in HA secretion following exposure to growth factors. Although HAS-1 mRNA was increased in synovial cells after exposure to TGF-beta1/IL-1beta, the magnitude of the change was far less than the effect on HA synthesis. Our data thus suggest that HAS gene usage is tissue specific, and the regulation by growth factors is unique for each HAS gene and is further modulated by cell-specific factors. In addition, regulation of HA biosynthesis appears to be multi-faceted, with control of HAS gene expression and mRNA levels being only one aspect of this process.

Base Sequence↗
PubMed2001

Inconsistent effects of the proline12 --> alanine variant of the peroxisome proliferator-activated receptor-gamma2 gene on body mass index in children and adolescent girls.

OBJECTIVE: To ascertain whether variation in peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear ligand-dependent transcription factor affecting both adipocyte differentiation and insulin sensitivity, influences body mass index (BMI). DESIGN: Association study. SETTING: Academic research environment. PATIENT(S): Children with premature pubic hair and adolescent girls with hyperandrogenism. INTERVENTION(S): Assay for P12A and P115Q variants and measure BMI. MAIN OUTCOME MEASURE(S): BMI and PPAR-gamma genotypes. RESULT(S): Fourteen subjects were heterozygous for P12A; two were homozygous. None carried the P115Q allele. No significant differences in BMI or basal androstenedione concentrations between P12 carriers and noncarriers were found. Thirty-nine subjects had BMI values at two time points; mean BMI was significantly greater in the P12A carriers at time point 2. Those P12A carriers obese at time point 1 became more obese; lean mutation carriers tended to remain lean. Annual rate of increase in BMI was significantly greater in the P12A carriers than the noncarriers. CONCLUSION(S): Our findings suggest that P12A may be a genetic marker indicating risk for obesity persisting into adolescence. Future studies are needed to determine whether the divergent effects of P12A persist into adulthood, to elucidate the mechanism of this effect, and to replicate our findings in other populations.

Amino Acid Sequence↗
PubMed2001

Prevalence of anemia in cancer patients undergoing radiation therapy.

Anemia is associated with reduced local tumor control and impaired quality of life in patients with several types of solid tumors. The prevalence of anemia in patients who present at radiation oncology departments has not been well documented, and the impact of anemia on the outcome of radiation therapy is not widely appreciated in the radiation oncology setting. In an ongoing study, we are retrospectively reviewing the medical charts of patients before and after radiation therapy at our institutions to determine the magnitude of the anemia problem in this population. Preliminary data are available for 574 randomly selected patients (52% female) seen between December 1996 and June 1999. At presentation, 41% of all patients were anemic (hemoglobin < 12 g/dL); by the end of radiation therapy, this percentage increased to 54%. The most common tumor types were prostate (16%), breast (14%), head and neck (12%), colorectal (11%), lung/bronchus (11%), and uterine-cervix (9%). Anemia was most prevalent in patients with uterine-cervical tumors (75%), increasing to 79% by the end of radiation therapy. The prevalence of lung/bronchus and colorectal cancer was 55% and 44%, respectively, at baseline and increased to 77% and 63%, respectively, after radiation therapy. For nearly all tumor types, the majority of patients had or developed mild to moderate anemia (hemoglobin 10.0 to 11.9 g/dL). These data show that anemia is widespread among patients seen in radiation oncology practices. However, the anemia is usually mild and readily correctable. Because anemia and hypoxia possibly associated with anemia are obstacles to local tumor control and maintenance of quality of life, strategies to reverse anemia should receive greater attention.

Anemia↗
PubMed2001

Time costs of caring for children with severe disabilities compared with caring for children without disabilities.

To assess time costs of caring for children with severe disabilities in the community compared to caring for children without disabilities, a diary- and questionnaire-based study was carried out. Sixteen complete data sets were obtained from families with children who have disabilities (mean age 8.7 years) and 31 complete data sets from families with normally developing children (mean age 4.9 years). Diagnoses in the study group included cerebral palsy, autism, Sanfillipo syndrome, lissencephaly, and osteogenesis imperfecta. Items of personal care per waking hour were significantly greater in children with disabilities than non-disabled children (p<0.001). In the study group, there was no correlation (r=-0.12) between age and frequency of care whereas a significant correlation was observed between degree of disability as measured by the Functional Independence Measure for children (WeeFIM) and frequency of care items (r=0.89). Twelve of the 16 mothers in the study group were not in paid employment. Twelve had little or no extended family support. Benefits awarded did not correlate with the degree of disability as measured by the WeeFIM (r=-0.11). Care needs of children with severe disabilities are significantly greater than those of non-disabled children and do not decrease with advancing age. Mothers of children with disabilities are unable to work outside the home because of these care needs. This brings the family income, even when benefits are included, to a level that is less than peer families with non-disabled children. A Functional Disability Score may help to achieve more appropriate allocation of state resources.

Child↗
PubMed2001

Psychological model for judicial decision making in emergency or temporary child placement.

In emergencies, family court judges must often make rapid decisions, without benefit of thorough information, that have significant impact on people's lives. Action-oriented research was used to develop a model that would bring psychosocial factors to the legal system for the purpose of enhancing the judicial decision-making process in emergency and temporary child placement cases.

Child↗
PubMed2001

Environmental associations with eczema in early life.

BACKGROUND: Although atopic eczema (AE) is a common disease, little is known about its causes. OBJECTIVES: To investigate the role of dietary and environmental factors associated with the development of AE by the age of 2 years. METHODS: A cohort of children was recruited before birth from a consecutive series of newly pregnant mothers presenting for antenatal care at three general practices in Ashford, Kent, U.K. Data up to the age of 2 years were available for 624 (97%) of the original cohort. AE was defined using components of the U.K. diagnostic criteria for AE, maternal report of doctor-diagnosed eczema and maternally reported eczema. Exposures of interest were family history of allergic disease, dietary and breastfeeding patterns, family size and exposure to indoor domestic allergens. RESULTS: The cumulative prevalence of AE using the U.K. diagnostic criteria was 14% (95% confidence interval, CI 11-17%). The prevalence of maternally reported doctor-diagnosed eczema was much higher (31%, 95% CI 27-35%) and almost half (45%) the mothers reported that their child had ever had eczema (95% CI 41-49%). The relationship between parental atopy, parental history of allergic disease and the child's eczema was consistently stronger for the mothers than the fathers. There was a marked increase in the prevalence of eczema with increasing maternal education and in less crowded homes, associations that remained significant after controlling for other factors. CONCLUSIONS: The associations with environmental factors are consistent with the hypothesis that more crowded houses, increased family size and birth order, which may possibly increase early exposure to infections, may offer protection from subsequent development of eczema.

Adult↗