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John V Lamont

Publications and source records attributed to John V Lamont.

7 recordsLinked to original sources

Heritability for plasma VEGF concentration in the Stanislas family study.

Vascular endothelial growth factor (VEGF), a key regulator of blood vessel function during angiogenesis, has been related to various diseases including atherosclerosis, neurodegenerative disorders and cancers. However, data about genetic determinants of its concentration in blood are scarce. The present study aimed at estimating additive genetic heritability, household component effect and the influence of 3 common VEGF polymorphisms on plasma VEGF concentration. A random sub-sample of 160 nuclear families (647 individuals), aging from 5 to 57, was obtained from the Stanislas Family Study. Plasma VEGF concentration was measured by a multiplexing ELISA and genotyping of the polymorphisms C(-460)T, G(405)C and C(936)T of the VEGF gene was carried out by RFLP. After adjustment for the influence of known environmental covariates, significant familial correlations were observed for plasma VEGF concentration (P< or = 0.01 and P< or = 0.001) for all the various pairs of relatives, except between spouses. In addition, variance component analysis showed no significant household common environment contribution to variability of this trait, while the genetic contribution accounted for 60.6% regardless of the 4 classes of relatives. Taking the three polymorphisms into account did not modify the variance components. These results show that plasma VEGF concentrations are under genetic control in healthy families and that none of the 3 candidate polymorphisms significantly altered heritability.

Adolescent↗

Association between TNF and IL-1 bloc polymorphisms and plasma MCP-1 concentration.

BACKGROUND: Circulating MCP-1 concentration was found to be increased in cardiovascular diseases and is of high interest in the list of biomarkers of atherosclerosis. TNF-alpha, LT-alpha, IL-1alpha and IL-1beta are four proinflammatory cytokines that regulate MCP-1 concentration in vitro. We hypothesized that specific genetic polymorphisms in TNF, LTA, IL-1A and IL-1B genes could modulate plasma MCP-1 concentration. METHODS: Plasma MCP-1 concentration was quantified with a biochip array analyzer in 395 adults from the Stanislas family study. TNF -308G>A, LTA 252A>G (A=TNFB2, G=TNFB1), IL-1A -889C>T and IL-1B 3954C>T were genotyped with a prototypic multilocus genotyping assay. RESULTS: Among the four polymorphisms studied only LTA 252A>G and TNF -308G>A were significantly associated with plasma MCP-1 concentration (p=0.005 and p=0.038, respectively) after adjustment for covariates (age, sex, smoking, monocyte count and hematocrit). Carriers of the 252A allele or the -308G had lower MCP-1 concentrations than carriers of the 252G or the -308A alleles, respectively. Moreover, as TNF and LTA genes were in linkage disequilibrium, the TNF bloc haplotypes were compared with respect to MCP-1 concentration, and a significant association (p=0.021) was observed, due only to the LTA polymorphism. This association remained significant even after adjustment for TNF-alpha and hs-CRP concentrations. CONCLUSION: A functional polymorphism within the TNF bloc could modulate MCP-1 concentration and seems more likely to be near to the LTA 252A>G polymorphism than to the TNF -308G>A one. In addition, the association found in healthy French adults is independent of other actors of inflammation such as TNF-alpha and hs-CRP.

Adult↗

Biological determinants of and reference values for plasma interleukin-8, monocyte chemoattractant protein-1, epidermal growth factor, and vascular endothelial growth factor: Results from the STANISLAS cohort.

BACKGROUND: Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) are known to be involved in various diseases related to inflammation, vascular remodeling, or growth deregulation. In addition, increases in plasma concentrations of these cytokines appear to provide useful diagnostic and prognostic information. We therefore investigated which factors most strongly influence the biological variations of plasma IL-8, MCP-1, EGF, and VEGF concentrations. METHODS: We used the Evidence biochip array analyzer to quantify plasma IL-8, MCP-1, EGF, and VEGF concentrations in a subsample of 304 children (age range, 4-17 years) and 540 adults (age range, 18-55 years) from the STANISLAS family study. We also calculated reference intervals for the 4 cytokines. RESULTS: We found the following associations with plasma marker concentrations: Age, neutrophil count, and glucose concentration were positively associated with IL-8 concentrations in children and adults, as were smoking and platelet count in adults. MCP-1 concentrations were associated with age and smoking in both children and adults, monocyte count in children, and sex and hematocrit in adults. EGF concentrations were associated with platelet count in children and monocyte count and glucose in adults. VEGF concentrations were associated with age in children and adults and platelet count and alanine aminotransferase activity in adults. CONCLUSION: Our results for IL-8, MCP-1, EGF, and VEGF may be useful for interpretation of patients' laboratory results and for understanding the regulation of concentrations of these cytokines in physiologic conditions.

Adolescent↗

Development of a high-throughput automated analyzer using biochip array technology.

BACKGROUND: Use of protein array technology over conventional assay methods has advantages that include simultaneous detection of multiple analytes, reduction in sample and reagent volumes, and high output of test results. The susceptibility of ligands to denaturation, however, has impeded production of a stable, reproducible biochip platform, limiting most array assays to manual or, at most, semiautomated processing techniques. Such limitations may be overcome by novel biochip fabrication procedures. METHODS: After selection of a suitable biochip substrate, biochip surfaces were chemically modified and assessed to enable optimization of biochip fabrication procedures for different test panels. The assay procedure was then automated on a dedicated instrument, and assay performance was determined for a panel of cytokine markers. Assay results were then compared with a commercial method for measurement of cytokine markers. RESULTS: Secondary ion mass spectrometry and x-ray photoelectron spectroscopy demonstrated appropriate and reproducible modification of the biochip surface. Contact-angle studies also confirmed generation of hydrophobic surfaces that enabled containment of droplets for fabrication of discrete test regions. Automation of the biochip assays on a dedicated instrument produced excellent cytokine marker performance with intra- and interassay imprecision <10% for most analytes. Comparison studies showed good agreement with other methods (r = 0.95-0.99) for cytokines. CONCLUSION: Performance data from this automated biochip array analyzer provide evidence that it is now possible to produce stable and reproducible biochips for output of more than 2000 test results per hour.

Autoanalysis↗

Automation of biochip array technology for quality results.

BACKGROUND: Proteomics' requirement for simultaneous measurement of multiple markers is now possible with biochip array technology. Many laboratories utilise in-house, manual procedures for biochip fabrication and sample testing. Reproducibility and standardisation of biochip processes is vital to ensure quality of results and offer the best tool for elucidation of complex relationships between multiple proteins in diseased conditions. METHODS: Various novel control checks have been implemented in biochip fabrication, reagent manufacture, automation and imaging processes for the Evidence analyser. Reference spots enable location of discrete test regions on the surface of the biochip and simultaneous quantification of multiple markers. Performance and standardisation methods are presented. RESULTS: Formulation of dispense solution for discrete test regions had a direct effect on their shape, stability and integrity on the biochip surface. Assays for fertility hormones and drugs of abuse demonstrated excellent precision, stability and comparison with other commercial methods. CONCLUSION: Control processes employed in the manufacture and analysis of Evidence components ensure reproducibility of assays for a range of routine and novel markers.

Animals↗

Serum total antioxidant status, erythrocyte superoxide dismutase and whole-blood glutathione peroxidase activities in the Stanislas cohort: influencing factors and reference intervals.

The aim of this work was to describe the factors influencing the levels of three antioxidant markers -total antioxidant status, erythrocyte copper/zinc superoxide dismutase (SOD), whole-blood selenium glutathione peroxidase--and to establish their reference intervals in supposedly healthy subjects. The studied population included 463 subjects, i.e., 223 adults and 140 children aged 20 to 65 and 4 to 19 years, respectively. The effect of factors such as age, gender, body mass index, alcohol and tobacco consumption, menopause, drug intake, trace elements, transferrin, ferritin, albumin, bilirubin, haptoglobin, total proteins, uric acid, haemoglobin, and mean corpuscular volume of erythrocytes have been studied for the three antioxidant markers. Total antioxidant status (TAS) was higher in men than in women whatever the age (p < 0.001). Albumin and uric acid in men, women and girls, and total proteins in boys were significant determinants of TAS levels. Mean corpuscular volume of erythrocytes were negatively and significantly associated with SOD activity in men and in women (p < 0.01) but not in children. Among the studied determinants, none were found to influence the selenium glutathione peroxidase activity in the four groups. Reference intervals including the 90% confidence intervals were established by age and sex for the three antioxidant markers.

Adolescent↗