209 research outputs found
Matrix-free calcium in isolated chromaffin vesicles
Isolated secretory vesicles from bovine adrenal medulla contain 80 nmol of Ca2+ and 25 nmol
of Mg2+ per milligram of protein. As determined with a Ca2+-selective electrode, a further accumulation
of about 160 nmol of Ca2+/mg of protein can be attained upon addition of the Ca2+ ionophore A23187.
During this process protons are released from the vesicles, in exchange for Ca2+ ions, as indicated by the
decrease of the pH in the incubation medium or the release of 9-aminoacridine previously taken up by the
vesicles. Intravesicular Mg2+ is not released from the vesicles by A23 187, as determined by atomic emission
spectroscopy. In the presence of N H Q , which causes the collapse of the secretory vesicle transmembrane
proton gradient (ApH), Ca2+ uptake decreases. Under these conditions A23 187-mediated influx of Ca2+
and efflux of H+ cease at Ca2+ concentrations of about 4 pM. Below this concentration Ca2+ is even released
from the vesicles. At the Ca2+ concentration at which no net flux of ions occurs the intravesicular matrix
free Ca2+ equals the extravesicular free Ca2+. In the absence of NH4C1 we determined an intravesicular
pH of 6.2. Under these conditions the Ca2+ influx ceases around 0.15 pM. From this value and the known
pH across the vesicular membrane an intravesicular matrix free Ca2+ concentration of about 24 pM was
calculated. This is within the same order of magnitude as the concentration of free Ca2+ in the vesicles
determined in the presence of NH4C1. Calculation of the total Ca2+ present in the secretory vesicles gives
an apparent intravesicular Ca2+ concentration of 40 mM, which is a factor of lo4 higher than the free
intravesicular concentration of Ca2+. It can be concluded, therefore, that the concentration gradient of free
Ca2+ across the secretory vesicle membrane in the intact chromaffin cells is probably small, which implies
that less energy is required to accumulate and maintain Ca2+ within the vesicles than was previously
anticipated
Cd19-negative relapse of pediatric b-cell precursor acute lymphoblastic leukemia following blinatumomab treatment
Magnetic field exposure and long-term survival among children with leukaemia
We examined the association between magnetic field (MF) exposure and survival among children with acute lymphoblastic leukaemia (ALL) treated at 51 Pediatric Oncology Group centres between 1996 and 2001. Of 1672 potentially eligible children under treatment, 482 (29%) participated and personal 24-h MF measurements were obtained from 412 participants. A total of 386 children with ALL and 361 with B-precursor ALL were included in the analysis of event-free survival (time from diagnosis to first treatment failure, relapse, secondary malignancy, or death) and overall survival. After adjustment for risk group and socioeconomic status, the event-free survival hazard ratio (HR) for children with measurements ⩾0.3 μT was 1.9 (95% confidence interval (CI) 0.8, 4.9), compared to <0.1 μT. For survival, elevated HRs were found for children exposed to ⩾0.3 μT (multivariate HR=4.5, 95% CI 1.5–13.8) but based on only four deaths among 19 children. While risk was increased among children with exposures above 0.3 μT, the small numbers limited inferences for this finding
The analysis of 2-amino-2-thiazoline-4-carboxylic acid in the plasma of smokers and non-smokers
ATCA (2-amino-2-thiazoline-4-carboxylic acid) is a promising marker to assess cyanide exposure because of several advantages of ATCA analysis over direct determination of cyanide and alternative cyanide biomarkers (i.e. stability in biological matrices, consistent recovery, and relatively small endogenous concentrations). Concentrations of ATCA in the plasma of smoking and non-smoking human volunteers were analyzed using gas-chromatography mass-spectrometry to establish the feasibility of using ATCA as a marker for cyanide exposure. The levels of ATCA in plasma of smoking volunteers, 17.2 ng/ml, were found to be significantly (p < 0.001) higher than that of non-smoking volunteers, 11.8 ng/ml. Comparison of ATCA concentrations of smokers relative to non-smokers in both urine and plasma yielded relatively similar results. The concentration ratio of ATCA for smokers versus non-smokers in plasma and urine was compared to similar literature studies of cyanide and thiocyanate, and correlations are discussed. This study supports previous evidence that ATCA can be used to determine past cyanide exposure and indicates that further studies should be pursued to validate the use of ATCA as a marker of cyanide exposure
Effect of synbiotic supplementation in children and adolescents with cystic fibrosis: a randomized controlled clinical trial
BACKGROUND/OBJECTIVES:Cystic fibrosis (CF) is characterized by excessive activation of immune processes. The aim of this study was to evaluate the effect of synbiotic supplementation on the inflammatory response in children/adolescents with CF.
SUBJECTS/METHODS:A randomized, placebo-controlled, double-blind, clinical-trial was conducted with control group (CG, n = 17), placebo-CF-group (PCFG, n = 19), synbiotic CF-group (SCFG, n = 22), PCFG negative (n = 8) and positive (n = 11) bacteriology, and SCFG negative (n = 12) and positive (n = 10) bacteriology. Markers of lung function (FEV1), nutritional status [body mass index-for age (BMI/A), height-for-age (H/A), weight-for-age (W/A), upper-arm fat area (UFA), upper-arm muscle area (UMA), body fat (%BF)], and inflammation [interleukin (IL)-12, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-1β, IL-8, myeloperoxidase (MPO), nitric oxide metabolites (NOx)] were evaluated before and after 90-day of supplementation with a synbiotic.
RESULTS:No significance difference was found between the baseline and end evaluations of FEV1 and nutricional status markers. A significant interaction (time vs. group) was found for IL-12 (p = 0.010) and myeloperoxidase (p = 0.036) between PCFG and SCFG, however, the difference was not maintained after assessing the groups individually. NOx diminished significantly after supplementation in the SCFG (p = 0.030). In the SCFG with positive bacteriology, reductions were found in IL-6 (p = 0.033) and IL-8 (p = 0.009) after supplementation.
CONCLUSIONS: Synbiotic supplementation shown promise at diminishing the pro-inflammatory markers IL-6, IL-8 in the SCFG with positive bacteriology and NOx in the SCFG in children/adolescents with CF
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia
Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered
Clinical Care Guidelines for Cystic Fibrosis–Related Diabetes: A position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society
Effects of exercise training on mobilization and functional activity of blood-derived progenitor cells in patients with acute myocardial infarction
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