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Biomedical subjects

J Wilkinson

Publications and source records attributed to J Wilkinson.

At least 73 records · Page 4Linked to original sources
PubMed1999

CD8+ anti-human immunodeficiency virus suppressor activity (CASA) in response to antiretroviral therapy: loss of CASA is associated with loss of viremia.

CD8+ anti-human immunodeficiency virus (HIV) suppressor activity (CASA) defines the noncytolytic suppression of HIV mediated by secreted soluble factors. Changes in CASA in patients receiving combination antiretroviral therapy have not been described. Thirty-two HIV-infected patients receiving mono- or dual therapy for 52 weeks followed by highly active antiretroviral therapy (HAART) for a further 52 weeks were analyzed. T cell number and functional subsets, cutaneous delayed-type hypersensitivity, and plasma HIV RNA were assessed in 17 patients for CASA. Prior to therapy, CASA correlated inversely with HIV RNA (P<.001). Dual therapy yielded greater and more sustained changes in CASA than monotherapy, but HAART decreased CASA to levels observed in HIV-uninfected individuals. The magnitude of HIV RNA suppression correlated significantly with a decrease in activated CD8+ T lymphocytes (CD38+HLA-DR+), increases in naive CD4+ T lymphocytes (CD45RA+62L+), and increases in the delayed-type hypersensitivity score. However, changes in CASA did not correlate with changes in any T lymphocyte subset. CASA increases with improving immune function but appears more dependent on ongoing HIV replication.

Anti-HIV Agents↗
PubMed1999

Molecular cloning and expression of Arabidopsis fatty acid hydroperoxide lyase.

Fatty acid hydroperoxide lyase (HPOL), an enzyme of the octadecanoid pathway that forms carbon-6 aldehydes such as n-hexanal or (Z)-3-hexenal, was cloned from Arabidopsis thaliana as a full-length cDNA. The HPOL activity obtained by expressing the cDNA in Escherichia coli formed n-hexanal from linoleic acid 13-hydroperoxide, whereas linoleic acid 9-hydroperoxide was not a substrate for the enzyme. The HPOL mRNA is expressed at low level in leaves; however, its accumulation can be found in the inflorescence. Wounding or methyl jasmonate treatments increase the mRNA level in leaves. These results indicate that the HPOL gene is up-regulated in leaves in response to wounding and that the enzyme may be an active component of the octadecanoid defense response.

Aldehyde-Lyases↗
PubMed1999

Adequacy of clinical formulae for estimation of energy requirements in children with cystic fibrosis.

BACKGROUND: Two clinical formulae (CF conference formula and estimation based on 120% of average requirement for energy) have been recommended for the estimation of energy requirements in cystic fibrosis but their accuracy is unknown. AIM: To compare the accuracy of estimates of energy requirement derived from the two formulae. METHODS: Energy requirement, defined as total daily energy expenditure, was measured using the doubly labelled water method in 15 patients (six girls, nine boys; mean (SD) age, 10.0 (2.4) years) who were well and clinically stable. The accuracy of the formulae was assessed using calculation of biases and limits of agreement relative to measured energy requirement. RESULTS: Estimates from the CF conference formula were lower than measured values (mean paired difference, 0.52 MJ/day; 95% confidence interval (CI), -1.10 to 0. 10), but this bias was not significant, and was smaller than that from the alternative formula (mean paired difference, 0.77 MJ/day; 95% CI, -0.20 to 1.74). Limits of agreement relative to measured total daily energy expenditure were narrower for the CF conference formula (-2.72 to 1.68 MJ/day) than for that based on 120% of estimated average requirement (-2.75 to 4.29 MJ/day), but with both formulae errors in estimation at the individual level were large. CONCLUSIONS: The CF conference formula offers improved prediction of energy requirements, but the accuracy of both formulae at the individual level is not sufficiently good for clinical purposes.

Adolescent↗
PubMed1998

Disruption of c-Fos leads to increased expression of NAD(P)H:quinone oxidoreductase1 and glutathione S-transferase.

Regulation of the basal and induced expression of detoxifying enzymes such as NAD(P)H:quinone oxidoreductasel (NQO1) and glutathione S-transferase (GST) by the antioxidant response element (ARE) is important for cellular protection against oxidative stress. The ARE contains AP1 and AP1-like elements and is known to bind to several leucine zipper proteins including c-Fos. Previous studies (Venugopal, R., and Jaiswal, A.K. (1996) Proc. NatL Acad. Sci. USA 93, 14960-14965) have shown that overexpression of c-Fos in transfected cells leads to repression of ARE-mediated gene expression. In the present report, we used c-Fos-/- mice and investigated the physiological (in vivo) role of c-Fos in repression of the NQO1 and GST genes expression. The analysis of enzyme activity levels showed significant increases in NQO1 and GST activities in several tissues of c-Fos-/- mice, as compared with wild type (c-Fos+/+) mice. The increases in enzyme activities were supported by Wetern analysis of respective proteins. Western analyses showed significant increases in the expression of NQO1 in kidney, liver and skin tissues of c-Fos-/- mice, as compared with wild type (c-Fos+/+) controls. Western analyses also demonstrated an increased expression of the GST Ya gene in kidney and liver tissues of the c-Fos-/-mice. These results confirm a negative (repressive) role for c-Fos in the expression of NQO1, GST Ya, and other detoxifying enzyme genes.

Animals↗
PubMed1998

Linkage of asthma to markers on chromosome 12 in a sample of 240 families using quantitative phenotype scores.

We present evidence of linkage between markers on chromosome 12 and asthma using the BETA program for nonparametric single- and multipoint linkage analysis. We have used quantitative scores as our phenotypic variables, combining data into indices for asthma and atopy and maximizing heritability. The largest single-locus LODs were achieved for asthma: D12S342 and asthma score (LOD 2.255), D12S324 and asthma affection (LOD 2.214), and D12S366 and wheeze (LOD 3.307). The region of interest identified using multipoint analysis, with a maximum LOD of 2.29, centers around D12S97 at location 173.5 cM with a standard error of 6.5 for the asthma score and close agreement for asthma affection and wheeze. Such evidence merits further investigation of this area in an attempt to define the region with greater precision with a view to identifying candidate genes. We hope that the methods presented will encourage researchers to use phenotypic information in a way that encourages meta-analysis.

Adolescent↗
PubMed1998

Characterization of SCML1, a new gene in Xp22, with homology to developmental polycomb genes.

Using exon trapping, we have identified a new human gene in Xp22 encoding a 3-kb mRNA. Expression of this RNA is detectable in a range of tissues but is most pronounced in skeletal muscle and heart. The gene, designated "sex comb on midleg-like-1" (SCML1), maps 14 kb centromeric of marker DXS418, between DXS418 and DXS7994, and is transcribed from telomere to centromere. SCML1 spans 18 kb of genomic DNA, consists of six exons, and has a 624-bp open reading frame. The predicted 27-kDa SCML1 protein contains two domains that each have a high homology to two Drosophila transcriptional repressors of the polycomb group (PcG) genes and their homologues in mouse and human. PcG genes are known to be involved in the regulation of homeotic genes, and the mammalian homologues of the PcG genes repress the expression of Hox genes. SCML1 appears to be a new human member of this gene group and may play an important role in the control of embryonal development.

Amino Acid Sequence↗
PubMed1998

Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study.

BACKGROUND: Congenital heart defects are generally assumed to have a multifactorial aetiology. We have tested this hypothesis by studying adults with heart defects and their families. METHODS: We identified 1094 patients who survived surgery for major cardiac defects before 1970. We chose individuals with disturbance of situs or segmental connection, with atrioventricular septal defect or with tetralogy of Fallot. After exclusion and non-participation, 727 individuals were traced. Each was visited by an investigator and completed a detailed questionnaire. If possible, all "normal" offspring were examined by a paediatric cardiologist. FINDINGS: The 727 individuals had 393 live offspring. There were 71 miscarriages and five terminated pregnancies. Overall, we found recurrent heart defects in 16 liveborn offspring--a recurrence risk of 4.1%. This result differed significantly from sibling risk (2.1%; p=0.021). More congenital heart defects occurred in the offspring of affected women than in those of affected men (p=0.047); when all malformations (cardiac and non-cardiac) in the offspring were taken into account the excess was more significant (p=0.032). We found an excess of miscarriages in the offspring of affected women (p=0.001). In tetralogy of Fallot, heart defects occurred in seven (3.1%) of 223 offspring, 12 (2.2%) of 539 siblings, five (0.3%) of 1575 second-degree relatives, and eight (0.3%) of 2728 third-degree relatives. INTERPRETATION: Our findings do not support a polygenic basis for all heart defects. Atrioventricular septal defect seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder with a small number of interacting genes. Our data suggest that isolated transposition of the great arteries is a sporadic defect.

Adult↗
PubMed1998

Identification of four novel mutations in patients with carnitine palmitoyltransferase II (CPT II) deficiency.

Carnitine palmitoyltransferase II (CPT II) deficiency, an autosomal recessive disorder of fatty-acid oxidation, presents as three distinct phenotypes (neonatal, infantile, and adult onset). In order to investigate the molecular basis of these three phenotypes, six patients with CPT II deficiency have been studied. All six unrelated patients in this study experienced the clinical symptoms of CPT II deficiency. Three patients had the neonatal form, one had the milder infantile form, and the remaining two had the adult-onset form with "muscular" symptoms only. Their diagnoses were based upon in vitro analysis of the mitochondrial beta-oxidation pathway in fibroblasts and standard enzyme assays. We devised a method to screen the entire coding sequence and flanking splice junction of the CPT II gene. A total of six different mutations have been identified, including four novel mutations. Among them, the previously reported common mutation, S113L, was only found in 3 of 12 variant alleles. Three of the six mutations have been identified in a few unrelated patients, while the remaining three have been found in single families. This study, as well as those by others, indicates genetic heterogeneity in this disease. In addition to tabulating the mutations, the correlation of mutant genotype to clinical phenotype is briefly discussed.

Adult↗
PubMed1998

Fractionated high dose rate brachytherapy moulds--a precise treatment for carcinoma of the pinna.

BACKGROUND AND PURPOSE: The aim of this paper is to describe a fractionated high dose rate brachytherapy procedure for the treatment of small superficial cancers of the pinna and to report the outcome in a small series of patients. MATERIALS AND METHODS: Thirteen patients with superficial cancers of the pinna, not invading cartilage, have been treated and in the majority of cases the tumour thickness was determined by a transdermal ultrasound measurement. For the single-plane moulds the prescribed surface dose was 45 Gy in eight fractions over 5 days and the moulds were constructed such that the full thickness of the disease, as determined by the ultrasound measurement, would lie within the 80% isodose surface. One case was treated with a sandwich mould and in this case the dose was reduced to 42.5 Gy. The treatment machine was a high dose rate microselectron, which contains a single stepping iridium source. RESULTS: The radiation reactions were of moderate severity, but were limited to the high dose volume. In all cases there was complete tumour resolution and rapid healing occurred leaving a barely perceptible scar. There were no recurrences over a minimum follow-up time of 18 months and there were no late radiation complications in this period. CONCLUSIONS: The treatment of superficial carcinoma of the pinna by means of HDR moulds is a safe and reliable technique. In this small series of patients there was total tumour control with excellent cosmesis.

Brachytherapy↗
PubMed1998

Perioperative artificial nutrition in elective surgery: an impact study of French guidelines.

OBJECTIVE: In France, the consensus conference, held on 16 December 1994, produced guidelines on perioperative artificial nutrition (AN) use in patients undergoing elective surgery. The aim of this study was to assess the impact of these guidelines on practice patterns. METHODS: The study was a practice pattern study with a 'before-after' design and a control group in England. A retrospective cross-sectional sample of adult patients undergoing elective resection of the digestive tract was collected in France and England before and after the consensus conference. RESULTS: Malnourished patients received postoperative AN in 94% of 'before' cases and 82% 'after' but inadequate preoperative AN (40% 'before' and 26% 'after'). Postoperative AN appeared to be over-prescribed in non-malnourished patients without prolonged postoperative fasting (70% 'before' and 65% 'after'). In the English sample there was no significant variation in AN use between 'before' and 'after' periods. CONCLUSION: This study shows that clinical guidelines disseminated by consensus conference had a low impact on practice patterns in France and thus confirms the need to enforce the dissemination of the guidelines.

Adult↗
PubMed1998

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Antigens, CD↗
PubMed1998

Metabolizable energy of high non-starch polysaccharide-maintenance and weight-reducing diets in men: experimental appraisal of assessment systems.

We have examined the reliability of several food energy assessment systems for healthy men. The predictions of metabolizable energies were compared with determinations made in energy balance studies with three maintenance diets (12 MJ/d); one of the diets was moderate in non-starch polysaccharide (NSP; 2.1% of gross energy) and two were higher in NSP (3.5-4.6% of gross energy). A fourth diet was a submaintenance (6 MJ/d) high NSP (7% gross energy) diet. Discrepancies between the different food energy assessment systems and the determined metabolizable energy values ranged between 0 and 15%. With the maintenance diets, the Atwater specific factor system had errors generally within 6% of the determined value and a limit of agreement (bias +2SD) for diets of 10%. This accuracy compares with errors of 2% for both the originally published assessment of this system and a more recent general formula; both systems were without bias with increasing NSP content of the diets but the latter had limits of agreement within 3%. In contrast, the Atwater general, the European general and a recent FDA general formula showed increasing bias with increasing NSP intake. All of the general energy assessment systems overpredicted metabolizable energy from the high NSP submaintenance diet, which shows that even the least biased and most reliable energy assessment system that we identified applies to maintenance diets only; thus a correction has to be made for submaintenance diets.

Adult↗
PubMed1998

Clinical morphology of sodium lauryl sulfate (SLS) and nonanoic acid (NAA) irritant patch test reactions at 48 h and 96 h in 152 subjects.

In this study of 152 women, comparison of patch test responses between 2 irritants over 96 h at 2 symmetrical anatomical sites is studied. 2 irritants, each at 4 different concentrations (nonanoic acid (NAA) 80%, 40%, 20%, 10%; sodium lauryl sulfate (SLS) 3%, 2%, 1% and 0.5%) and using propan-1ol and 'water for injection' as the respective controls, were placed as 15 microl aliquots, soaked onto filter paper discs in Finn Chambers, on the volunteer's left and right lower back. The patches were removed at 47, and read at 48 and 96 h. Irritant reactions were evaluated for erythema and surface changes by degree and area affected. Statistical analysis of the results showed that erythema decreased with time for all concentrations of NAA, and at higher concentrations for SLS. Surface changes increased with time for SLS and at higher concentrations of NAA. There was no statistically significant difference comparing left and right sides. Traditionally in patch testing, reactions which fade after 48 h have been regarded as irritant rather than allergic. This study refutes that assumption. Data from our left to right comparisons, made in the same individuals at the same time, show that irritant reactions may be more reproducible than previously appreciated.

Adolescent↗