Comparative analyses of the studies of magnetic fields and cancer in electric utility workers: studies from France, Canada, and the United States.
(9/1081)
OBJECTIVES: To summarise and to facilitate comparison of three major studies of electric utility workers that examined the relation between quantitative measurements of occupational exposure to magnetic fields and risk of brain cancer and leukaemia. These studies have been interpreted as providing conflicting evidence. METHODS: A common analytical approach was applied to data from the five cohorts included in the three studies based on original data from four of the cohorts, and published data from one additional cohort. A nested case-control design with conditional logistic regression was used to estimate the relative risk/10 microtesla-years (microT-years) for each of the contributing cohorts and for the combined data. The homogeneity of these estimates among the studies was also evaluated. RESULTS: Apparent inconsistencies in the findings of these studies can be explained by statistical variation. Overall, the studies suggest a small increase in risk of both brain cancer and leukaemia. Different methodological choices had little impact on the results. Based on a combined analysis of data from all five studies, the relative risk/10 microT-years was 1.12 (95% confidence interval (95% CI) 0.98 to 1.28) for brain cancer, and 1.09 (95% CI 0.98 to 1.21) for leukaemia. CONCLUSIONS: The combined estimates seem to provide the best summary measures of the data from all studies. However, fluctuations in risks among studies may reflect real differences, and the exposure measurements in different studies may not be entirely comparable. (+info)
New electrochemiluminescent immunoassay for the determination of CYFRA 21-1: analytical evaluation and clinical diagnostic performance in urine samples of patients with bladder cancer.
(10/1081)
BACKGROUND: A new electrochemiluminescent immunoassay (ECLIA) has been developed for the determination of cytokeratin 19 (CYFRA 21-1) in the Elecsys 2010 immunoassay system. Urinary CYFRA 21-1 might have a role in the diagnosis of bladder cancer. METHODS: We performed an analytical evaluation of the CYFRA 21-1 ECLIA for serum and urine samples. The clinical value of urinary CYFRA 21-1 for the detection of bladder cancer was evaluated through its measurement in 226 urine samples from symptomatic and asymptomatic controls. RESULTS: At concentrations of 2-30 microg/L, within-assay imprecision (CV) was below 2.1% for sera and 3.3% for urines, with interassay CVs below 3.3% for sera and 4.9% for urines. The day-to-day CV was <20% at concentrations >0.2 microg/L (functional sensitivity). Measurement of diluted samples showed that the assay estimated CYFRA 21-1 between 98% and 103% for sera and 98% and 105% for urines. Recovery of added CYFRA 21-1 was 99-105% for sera and 96-115% for urines. We separately compared serum and urine CYFRA 21-1 ECLIA results with those obtained with an IRMA (CIS bio international). Regression analysis for sera was: CYFRA 21-1 (ECLIA) = 0.520 + 1.018 CYFRA 21-1 (IRMA); [95% confidence interval (CI) (y-intercept), -0.260 to 1.309]; 95% CI (slope), 0.978-1.060; n = 100; S(y|x) = 3.242; r(2) = 0.987. For urine samples it was: CYFRA 21-1 (ECLIA) = 0.716 + 0.966 CYFRA 21-1 (IRMA); 95% CI (y-intercept), 0.009-1.422; 95% CI (slope), 0.956-0.976; n = 100; S(y|x) = 4.136; r(2) = 0.986. In urine samples voided by patients with and without bladder cancer, the best ROC analysis discrimination provided 81.0% (95% CI, 72.7-87.7%) sensitivity and 97.2% (95% CI, 90.2-99.6%) specificity at a threshold value of 5.7 microg/L. CONCLUSIONS: Our initial evaluation showed reliable analytical performance for urinary CYFRA 21-1, which might assist urologists in the detection of bladder cancer as a noninvasive adjunct to cystoscopy. (+info)
Molecular dynamics study of the KcsA potassium channel.
(11/1081)
The structural, dynamical, and thermodynamic properties of a model potassium channel are studied using molecular dynamics simulations. We use the recently unveiled protein structure for the KcsA potassium channel from Streptomyces lividans. Total and free energy profiles of potassium and sodium ions reveal a considerable preference for the larger potassium ions. The selectivity of the channel arises from its ability to completely solvate the potassium ions, but not the smaller sodium ions. Self-diffusion of water within the narrow selectivity filter is found to be reduced by an order of magnitude from bulk levels, whereas the wider hydrophobic section of the pore maintains near-bulk self-diffusion. Simulations examining multiple ion configurations suggest a two-ion channel. Ion diffusion is found to be reduced to approximately 1/3 of bulk diffusion within the selectivity filter. The reduced ion mobility does not hinder the passage of ions, as permeation appears to be driven by Coulomb repulsion within this multiple ion channel. (+info)
Dynamics of oscillating erythrocyte doublets after electrofusion.
(12/1081)
Erythrocytes were electrofused with multiple rectangular voltage pulses to show an oscillatory movement, divided into swell phases and pump events. During each swell phase, which lasted from 0.5 s to more than 180 s, the fused cells' (doublets') volume increased by colloid osmotic swelling, and the membrane area was expanded until rupture. Membrane rupture initiated the pump event, where the doublets' volume and membrane area decreased with an almost exponential time course and time constants between 2 ms and 8 ms. Simultaneously, a portion of cytosolic hemoglobin solution was ejected into extracellular space ("jet"). Pump event time constants and swell phase durations decreased with rising chamber temperature, indicating that both parts of the oscillatory movements were determined by physical properties of membrane and liquids. Relative volume change developments express a gradual loss of membrane elasticity during the oscillation, decreasing the elastic forces stored in the membrane. Evidence is given that the first rupture causes a weakening of the membrane at the rupture site. Heat treatment up to 45 degrees C had a negligible effect on swell times, pump time constants, and relative volume changes. A heat treatment of 50 degrees C prevented oscillatory movements. The rupture location accorded with theories of potential induced membrane electropermeabilization. (+info)
Intercalation of proflavine and a platinum derivative of proflavine into double-helical Poly(A).
(13/1081)
The equilibria and kinetics of the interactions of proflavine (PR) and its platinum-containing derivative [PtCl(tmen)(2)HNC(13)H(7)(NHCH(2)CH(2))(2)](+) (PRPt) with double-stranded poly(A) have been investigated by spectrophotometry and Joule temperature-jump relaxation at ionic strength 0.1 M, 25 degrees C, and pH 5.2. Spectrophotometric measurements indicate that base-dye interactions are prevailing. T-jump experiments with polarized light showed that effects due to field-induced alignment could be neglected. Both of the investigated systems display two relaxation effects. The kinetic features of the reaction are discussed in terms of a two-step series mechanism in which a precursor complex DS(I) is formed in the fast step, which is then converted to a final complex in the slow step. The rate constants of the fast step are k(1) = (2.5 +/- 0.4) x 10(6) M(-1) s(-1), k(-1) = (2.4 +/- 0.1) x 10(3) s(-1) for poly(A)-PR and k(1) = (2.3 +/- 0.1) x 10(6) M(-1) s(-1), k(-1) = (1.6 +/- 0.2) x 10(3) s(-1) for poly(A)-PRPt. The rate constants for the slow step are k(2) = (4.5 +/- 0.5) x 10(2) s(-1), k(-2) = (1.7 +/- 0.1) x 10(2) s(-1) for poly(A)-PR and k(2) = 9.7 +/- 1.2 s(-1), k(-2) = 10.6 +/- 0.2 s(-1) for poly(A)-PRPt. Spectrophotometric measurements yield for the equilibrium constants and site size the values K = (4.5 +/- 0.1) x 10(3) M(-1), n = 1.3 +/- 0.5 for poly(A)-PR and K = (2.9 +/- 0.1) x 10(3) M(-1), n = 2.3 +/- 0.6 for poly(A)-PRPt. The values of k(1) are similar and lower than expected for diffusion-limited reactions. The values of k(-1) are similar as well. It is suggested that the formation of DS(I) involves only the proflavine residues in both systems. In contrast, the values of k(2) and k(-2) in poly(A)-PRPt are much lower than in poly(A)-PR. The results suggest that in the complex DS(II) of poly(A)-PRPt both proflavine and platinum residues are intercalated. In addition, a very slow process was detected and ascribed to the covalent binding of Pt(II) to the adenine. (+info)
Identification of MUC5B, MUC5AC and small amounts of MUC2 mucins in cystic fibrosis airway secretions.
(14/1081)
To investigate the genetic identities of the mucins secreted in cystic fibrosis (CF) airways, sputum was collected from five individuals. Samples were separated into gel and sol phases by high-speed centrifugation and the gel phase was extracted in 6 M guanidinium chloride. The 'insoluble' residue remaining after extraction of the gel phase was brought into solution by reduction/alkylation. Density-gradient centrifugation in CsCl revealed polydisperse distributions of sialic acid-containing mucins in the gel phase, insoluble residue and sol phase fractions and the degree of variation between the different individuals was low. Antibodies recognizing MUC5AC and MUC5B identified these mucins in each of the fractions. MUC2, however, was present only as a component of the insoluble residue from the gel which accounted for less than 4% by mass of the total mucins. MUC5B and MUC5AC from the gel phase were large oligomeric species composed of disulphide-bond linked subunits and MUC5B was present as two populations with different charge densities which are likely to correspond to MUC5B 'glycoforms'. The sol phase contained, in addition to MUC5AC and MUC5B, mainly smaller mucins which did not react with the antisera and which were probably degraded. MUC5AC appeared to be enriched in the sol, suggesting that this mucin may be more susceptible to proteolytic degradation than MUC5B. The mucins present in sputum remained broadly similar during acute exacerbation and following antibiotic treatment, although the relative amount of an acidic MUC5B glycoform was decreased during infection. (+info)
Involucrin-positive keratinocytes demonstrate decreased migration speed but sustained directional migration in a DC electric field.
(15/1081)
When skin is wounded, keratinocytes from the cut edges of the epidermis migrate over the wounded area to re-epithelialize the wound. It is not clear which cells of the epidermis have the capacity to migrate and contribute to this re-epithelialization: the less differentiated cells of the basal layer, or the more differentiated, involucrin-positive suprabasilar cells. Here we demonstrate that both involucrin-negative and involucrin-positive cells are able to respond to a directional cue for migration with sustained directional migration. When cultured keratinocytes are exposed to a physiologic DC electric field of 100 mV per mm as a cue to guide migration (galvanotaxis) they migrate toward the cathode with equivalent directionality. The involucrin-positive cells, however, display mean migration speeds approximately one half (23.6 microm per h) of the mean rate achieved by involucrin-negative cells (46.5 microm per h). Despite their decreased migration rates, involucrin-positive cells appear to possess an intact mechanism for sensing a directional signal, transducing that signal, and responding with sustained directional migration. Because electric fields are endogenous in skin wounds, it is likely that both the basal, involucrin-negative cells and the involucrin-positive suprabasilar cells respond to this cue with directional migration. The new observation that involucrin-positive cells can indeed migrate suggests that these cells may also contribute to wound re-epithelialization in vivo. (+info)
Effect of cell shape on dielectric behavior of fission yeast.
(16/1081)
In order to study the effect of cell shape on dielectric behavior of cell suspensions, a temperature sensitive cell division cycle mutant cdc25-22, of Schizosaccharomyces pombe was used, whose cell length was varied by cultivating at the restrictive temperature. The dielectric dispersion of the cells in suspension was mainly composed of two subdispersions. The low-frequency subdispersion depended on the cell length, whereas the high-frequency subdispersion was independent of it. The cell shape effect was qualitatively simulated by an ellipsoidal cell model. (+info)