Principles and applications of luminescence spectrometry coupled to liquid chromatographic techniques

An overview is presented of the physicochemical basis of luminescence, and its application to the detection of chemicals (drugs, biomedically important compounds, environmentally active substances) in liquid chromatographic systems.     

The impact of the Scheldt input on the trace metal distribution in the Belgian coastal area (results of 1981–1983 and 1995–1996)

Offshore fluxes of Cu, Zn, Cd, Pb and Hg were calculated based onresidual flow patterns and salinity gradients along the Belgian coast. Theresidual flow lines along the Belgian coast are more or less parallel to thecoast except in the area where the north-easterly flowing watermass comingfrom the Channel encounters the south-westerly-oriented Scheldt outflow,forming a residual hydrodynamical front. From the steady-state salinitypattern, diffusion coefficients perpendicular to the residual flow werededuced; they ranged from 21 to 108 m² s^-1. Offshore fluxes of dissolved and particulate trace metals based on diffusiveand mixing processes are calculated. The steady state profiles of dissolvedmetals show a dilution effect in the coastal waters, reaching an almostconstant concentration in the marine watermass in the 1981–1983dataset. The ratios of the Scheldt input of trace metals to the totaldissolved offshore flux vary from 38 to 55% (1981–1983),depending on the kind of metal, and from 55 to 91% (1995–1996).The ratio of the Scheldt input to the dissolved metal flow parallel to thecoast, is in both periods (1981–1983 and 1995–1996), smallerthan 1%. The steady-state concentration profiles of particular metalsversus salinity are fairly constant in the coastal-estuarine and marinewatermasses, but decrease very abruptly from the first to the secondwatermass. Assuming a conservative behaviour of the particular metals,offshore fluxes and the resulting concentration increases agree fairly wellwith the observed values. The ratios of the Scheldt input to the particulatetrace metal offshore flux vary between 30 to 46% (1981–1983)and 13 to 37% (1995–1996). The contribution of the Scheldtestuary to the flows parallel to the coast ranges from 1.6 to 2.9%(1981–1983) and from 0.6 to 1.6% (1995). This revised version was published online in July 2006 with corrections to the Cover Date.     

Effects of low-chloride solutions on action potentials of sheep cadiac purkinje fibers

The rapid repolarization during phase 1 of the action potential of sheep cardiac purkinje fibers has been attributed to a time- and voltage-dependent chloride current. In part, this conclusion was based on experiments that showed a substantial slowing of phase 1 when larger, presumably impermeant, anions were substituted for chloride in tyrode’s solution. We have re- examined the electrical effects of low-chloride solutions. We recorded action potentials of sheep cardiac purkinje fibers in normal tyrode’s solution and in low-chloride solutions made by substituting sodium propionate, acetylglycinate, methylsulfate, or methanesulfonate for the NaCl of Tyrode’s solution. Total calcium was adjusted to keep calcium ion activity of test solutions equal to that of control solutions. Propionate gave qualitatively variable results in preliminary experiments; it was not tested further. Low-chloride solutions made with the other anions gave much more consistent results: phase 1 and the notch that often occurs between phases 1 and 2 were usually unaffected, and the action potential duration usually increased. The only apparent change in the resting potential was a transient 3-6 mV depolarization when low-chloride solution was first admitted to the chamber, and a symmetrical transient hyperpolarization when chloride was returned to normal. If a time- and voltage-dependent chloride current exists in sheep cardiac purkinje fibers, our results suggest that it plays little role in generating phase 1 of the action potential.     

Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)⁺ progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3⁺ cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increased the total number of islets. β cells proliferated without extended delay (the so-called ‘refractory'' period), their proliferation potential was highest in small islets, and 86% of the β cell expansion was attributable to proliferation of pre-existing β cells. At sufficiently high Ngn3 expression level, upto 14% of all β cells and 40% of small islet β cells derived from non-β cells. Moreover, β cell proliferation was blunted by a selective ablation of Ngn3⁺ cells but not by conditional knockout of Ngn3 in pre-existing β cells supporting a key role for Ngn3⁺ insulin⁻ cells in β cell proliferation and expansion. We conclude that Ngn3⁺ cell-dependent proliferation of pre-existing and newly-formed β cells as well as reprogramming of non-β cells contribute to in vivo β cell expansion in the injured pancreas of adult mice.     

Optimization of the chiral separation of some 2-arylpropionic acids on an avidin column by modeling a combined response

The enantiomeric separation of some nonsteroidal antiinflammatory drugs was investigated on an avidin column. An experimental design approach (central composite design) was used to evaluate the effects of three method parameters (pH, concentration of organic modifier, and buffer concentration) on the analysis time and the resolution, as well as to model these responses. This revealed that the organic modifier concentration and sometimes the pH are significant parameters to control because of their influence on both analysis time and resolution. Furthermore, the central composite design results were combined in a multicriteria decision-making approach in order to obtain a set of optimal experimental conditions leading to the most desirable compromise between resolution and analysis time.     

The micronucleus and G2-phase assays for human blood lymphocytes as biomarkers of individual sensitivity to ionizing radiation: limitations imposed by intraindividual variability

As part of a program to assess the applicability of the micronucleus (MN) and G2-phase assays as biomarkers of cancer susceptibility, we investigated the inter- and intraindividual variations of these end points. For the MN assay, unstimulated blood cultures from 14 healthy donors were exposed in vitro to 3.5 Gy 60Co gamma rays; for the G2-phase assay, PHA-stimulated cell cultures were irradiated with a dose of 0.4 Gy 60Co gamma rays in the G2 phase of the cell cycle. Two of the 14 volunteers were assayed 9 times over a period of 1 year. The repeat experiments revealed that the intraindividual variability was not significantly different from the interindividual variability for both the G2-phase and MN assays. Since the intraindividual variability determines the reproducibility of the assay, our results highlight the limitations of these end points in detecting reproducible differences in radiation sensitivity between individuals within a normal population. For example, one donor of the population was identified as being radiosensitive (based on the 90th percentile criterion) but turned out to be normal when the assay was repeated twice. We conclude that the determination of individual radiosensitivity with these two cytogenetic assays is unreliable when based on one blood sample.     

Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts

Background  

Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction.     

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.