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Biomedical subjects

M Gilson

Publications and source records attributed to M Gilson.

At least 19 recordsLinked to original sources
PubMed1999

The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder.

The relationship of the DRD2 TaqI-A1 allele to hyperactive/impulsive and inattentive symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents was examined in a sample of clinic-referred children and their siblings, and control children and their siblings (n = 236). The contribution of genetic dominance and additivity to mean differences among the A2A2, A1A2, and A1A1 genotypes was estimated using structural equation modeling. The effect of genetic additivity was statistically significant for both traits in an analysis of all children. The heritability from the DRD2 locus was estimated at 4.27% for hyperactive-impulsive symptoms and 2.12% for inattentive symptoms. Children with the A2A2 genotype had the highest mean level of symptoms. To control for any possible effects of population stratification, this analysis was repeated with parental genotypes as controls. In this smaller sample, although the direction of the effect was the same as that in the whole sample, the genotypic differences failed to reach conventional significance levels and the effect sizes were smaller (h2 = 1.62% and 0.79%, respectively). Furthermore, a genotype relative risk test of children who had questionnaire-based diagnoses of ADHD also failed to yield evidence of either association or linkage. Given that the A1 allele was expected to be the high risk allele, and that results were non-significant in tests that controlled for population heterogeneity, we doubt that this DRD2 polymorphism influences symptoms of ADHD in childhood.

Adolescent↗
PubMed1997

pKa measurements from nuclear magnetic resonance for the B1 and B2 immunoglobulin G-binding domains of protein G: comparison with calculated values for nuclear magnetic resonance and X-ray structures.

Two-dimensional homo- and heteronuclear nuclear magnetic resonance (NMR) spectroscopy was used to determine pKa values for all of the acidic residues in the B1 and B2 immunoglobulin G- (IgG-) binding domains of protein G. Due to the stability of protein G over a wide pH range, estimates of ionization constants were also obtained for some basic residues. These experimentally determined ionization constants were compared with values calculated from both X-ray and NMR-derived structures of B1 and B2 using the UHBD algorithm [Antosiewicz, J., et al. (1994) J. Mol. Biol. 238, 415-436]. This algorithm has been found to be predictive for pKa measurements in proteins and, in combination with experimental measurements, allowed some evaluation of the NMR and X-ray structures. Three regions where significant differences exist between the X-ray and NMR structures are (1) the position of the E56 side chain relative to the backbone amides of K10 and D40, (2) residues 33-37 in the helix, and (3) the Y45 side-chain conformation. For all three cases, the experimental pH titration curves are notably more consistent with the X-ray structures than the NMR structures. In contrast, a number of solvent-accessible side chains have experimental pKas more in agreement with mean pKas calculated from families of NMR structures. The conformations of these side chains may be susceptible to crystal packing effects. From titration experiments under basic conditions, it is noteworthy that the chemical shift of the Y45 C epsilonH resonance is invariant up to pDcorr 12. The Y45 side-chain hydroxyl group appears to maintain a nativelike hydrogen bond with D47 at pDcorr 12, even though the protein is approximately 90% unfolded. These results suggest that this short-range (i, i + 2) interaction, located in the beta3-beta4 hairpin, is present in the high-pH denatured state and may therefore form early in the folding of protein G.

Aspartic Acid↗
PubMed1994

Positron emission tomographic measurements of absolute regional myocardial blood flow permits identification of nonviable myocardium in patients with chronic myocardial infarction.

OBJECTIVES: This study tested the hypothesis that nonviable myocardium can be identified by quantitative measurements of regional myocardial blood flow obtained using positron emission tomography in conjunction with a mathematical model of nitrogen-13 (N-13) ammonia tracer kinetics. BACKGROUND: Under steady state basal conditions there is a minimal level of blood flow required to sustain myocardial viability. Therefore, the hypothesis predicts that regions with flow below a certain threshold are likely to be composed primarily of scar. METHODS: Studies were conducted in 26 patients with chronic myocardial infarction. Positron emission tomographic measurements of basal regional myocardial blood flow (N-13 ammonia) and fluorine-18 (F-18) fluorodeoxyglucose uptake were made and correlated with information about coronary anatomy and regional wall motion to assess myocardial viability. RESULTS: In patients with chronic myocardial infarction, normal zone blood flow (0.81 +/- 0.32 ml/min per g [mean +/- SD]) was greater (p < 0.02) than that of border zones (0.59 +/- 0.29 ml/min per g), which in turn exceeded (p < 0.001) that of infarct zone flow (0.27 +/- 0.17 ml/min per g). Good correlation was noted between relative F-18 fluorodeoxyglucose uptake and relative regional myocardial blood flow in all zones (r = 0.63, p < 0.001). Mismatch between blood flow and F-18 fluorodeoxyglucose uptake, with a single exception, was not observed in any segment with blood flow < 0.25 ml/min per g. All dyskinetic segments (n = 5) also had blood flow < 0.25 ml/min per g. In contrast, 43 of 45 myocardial segments (23 patients) with normal contraction or only mild hypokinesia had flow > or = 0.39 ml/min per g (average flow 0.78 +/- 0.35 ml/min per g). CONCLUSIONS: In patients with chronic myocardial infarction, myocardial viability is unlikely when basal regional myocardial blood flow is < 0.25 ml/min per g. Average basal flow in segments with normal or nearly normal wall motion is 0.78 +/- 0.35 ml/min per g. Thus, positron emission tomographic measurement of regional myocardial blood flow is helpful in identifying nonviable myocardium in these patients.

Adult↗
PubMed1994

Adaptive responses of coronary circulation and myocardium to chronic reduction in perfusion pressure and flow.

We tested the hypothesis that chronic reduction in perfusion pressure and flow in the coronary circulation induces a state of myocardial "hibernation" characterized not only by a steady-state reduction in myocardial O2 consumption (MVO2) but also by evidence of persistent dilator reserve of the distal vasculature. Biochemical and morphological changes in the coronary vasculature were also assessed. Experiments were conducted in swine with an extraluminal coronary stenosis placed 4-32 wk before study. Stenosis reduced lumen diameter by approximately 80% at the time of final experimentation. Baseline, regional myocardial blood flow distal to the stenosis in both endocardial and epicardial layers was reduced vs. that of the normal zone. Vasodilator reserve persisted in both endocardial and epicardial layers of the stenosis zone. Flow increased in each layer in response to adenosine plus phenylephrine and failed to decline despite a marked reduction in perfusion pressure in response to adenosine alone. Regional MVO2 at baseline was reduced vs. historical controls without coronary stenosis. Protein synthesis rate in coronary vessels of the stenosis zone was reduced vs. that of the normal zone. Morphological responses of stenosis zone vessel walls were heterogeneous. Smaller microvessels exhibited mild hypertrophy of their walls, whereas walls of larger microvessels tended to atrophy. Thus chronic reduction in perfusion pressure and flow induces a state of myocardial hibernation characterized by a steady-state reduction in MVO2 in association with persistent dilator capacity. Biochemical and morphological changes occur in microvessel walls and may contribute to observed physiological responses.

Acclimatization↗
PubMed1988

Assembly of Rubisco from native subunits.

Large subunits of ribulosebisphosphate carboxylase/oxygenase (Rubisco) (3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39) from prokaryotic sources can assemble into intact enzyme either in vitro or in Escherichia coli cells. Large subunits of higher plant Rubisco do not assemble into Rubisco in E. coli cells, nor is it possible to reconstitute higher plant Rubisco from its dissociated subunits in vitro. This behavior represents an obstacle to any practical attempts at engineering the higher plant enzyme, and it suggests that the in vivo assembly mechanism of higher plant Rubisco must be more complex than is commonly expected for oligomeric proteins of organelles. In pea chloroplasts, a binding protein interacts with newly synthesized large subunits, in quantities expected for an intermediate in the assembly process, as judged by Western blotting. Radiotracer-labeled large subunits which interact with this binding protein can be shown to assemble into Rubisco in reactions which lead to changes in the aggregation state of the binding protein. Antibody to this binding protein specifically inhibits the assembly of these subunits into Rubisco. Rubisco synthesis appears to be subject to many types of control: gene dosage, transcription rate, selective translation of message, post-translational degradation and threshold concentration effects have been observed in various organisms' synthesis of Rubisco. The biochemical mechanisms underlying most of these effects have not been elucidated. The post-translational assembly mechanism in particular appears to require further study.

Adenosine Triphosphate↗
PubMed1979

[Implantation of Binkhorst's iridocapsular lens (author's transl)].

Advantages of the extracapsular extraction for implantation of Binkhorst's iridocapsular lens. Description of the surgical procedure; its indications and contre indications. Analysis of the results of 131 operations. The follow up of 120 patients exceeded six months. 84% of the patients have a visual acuity higher than 10/20. The major complication is secondary cataract which requires new surgery in 20% of the cases. The major complication is secondary cataract which requires new surgery in 20% of the cases. Other complications are the same as in classical intracapsular extraction when the indications of iridocapsular implants are correct.

Aged↗