Risk factors for wheezing in Ukrainian children: Ukraine European Longitudinal Study of Pregnancy and Childhood Group

The prevalence of wheezing in children varies widely around the world. The reasons for this geographic variability remain unclear but may be related in part to exposures in the home environment during pregnancy and early childhood. We investigated the prenatal and early childhood risk factors for wheezing symptoms among 2127 children aged 6–8 years who were participants in the Ukrainian component of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). Cases included the 169 children whose parents answered yes to the International Study of Asthma and Allergy in Children (ISAAC) question: 'Has your child had wheezing or whistling in the chest in the past 12 months' during the ELSPAC assessment of the children at age 7. These were compared with the 1861 children in the cohort whose parents answered 'no' to this question.
Factors significantly associated with increased risk of wheezing illness at age 7 in adjusted analyses included mother's asthma [adjusted odds ratio (OR) 3.46, 95% confidence interval (CI) 1.22, 9.85]; mother's allergy problems (OR 1.43, [1.00, 2.05]); rarely playing with other children at age 3 (OR 1.84, [1.09, 3.11]); water intrusion (OR 1.62, [1.09, 2.39]) and inadequate heating of the home (OR 1.52, [1.06, 2.16]) during pregnancy. Factors protective of wheezing at age 7 included being first-born (adjusted OR 0.70, 95% CI 0.50, 0.98); living in the city of Dniprodzerzynsk as compared with Kyiv (OR 0.36, [0.24, 0.54]) and weekly contact with furry animals (OR 0.44, [0.20, 0.97]) before age 3. The constellation of risk factors for wheezing in Ukrainian children is similar to that of children in other parts of the world. Known risk factors do not account for the significant between-city variability of wheezing in Ukrainian children.     

Synthesis of boron-containing heterocyclic compounds.

The synthesis of boron-containing 1,3,5-triazines and 1,2,4-triazines is described. Derivatives of 1,3,5-triazine containing the o-carborane cluster have been obtained by reacting the corresponding propargyl derivatives with B(10)H(14). Derivatives of 1,2,4-triazine containing the B(12)H(12)(2-) cluster have been obtained by nucleophilic substitution of ethylsulfone derivatives with B(12)H(11)SH(2-). They have been isolated in their ring-protonated form. Reaction of RNH(2)-B(8)H(11)NH-R with stericly demanding heterocycles failed, either for steric or for solubility reasons.     

Self‐Assembly of Dendritic Macromolecules Based on the Ionic Interaction of Linear Chain Polyelectrolyte Cores with Oppositely Charged Focal Ionogenic Groups of Dendrons

Summary: A new principle for the design of dendritic macromolecules – the ionic binding of linear chain polyelectrolyte with oppositely charged focal ionogenic groups of dendrons – has been developed. The majority of the dendritic ionic complexes (DICs) are prepared with poly(styrenesulfonic acid) (PSS) as a polymeric core and L ‐aspartic acid dendrons of different generations. Two series of DICs were prepared using PSS and aspartic dendrons bearing terminal (located at the external periphery) methoxycarbonyl and hexyloxycarbonyl groups (C1‐n and C6‐n respectively where n is the generation number). Ionic binding of about 100% was found for dendrons of Generation 1–3. The solubility of the DICs was examined and the DICs prepared were studied by IR spectroscopy, ¹H NMR and viscometry.

Dendritic ionic complexes prepared using poly(styrenesulfonic acid) acid and aspartic dendrons bearing terminal methoxycarbonyl and hexyloxycarbonyl groups.     

Voltage-gated potassium currents in rat vas deferens smooth muscle cells

Voltage-gated components of the outward current in single smooth muscle cells isolated from the epididymal part of the rat vas deferens were studied using amphotericin B perforated patch-clamp techniques. The complex kinetics of the net outward current elicited by positive voltage steps from -80 mV to +40 mV suggested the presence of several components. Bath application of 200 nM charybdotoxin, a potent blocker of large-conductance, Ca(2+)-dependent K(+) channels (BK(Ca)), reduced the current amplitude significantly. When BK(Ca) channels were suppressed, fast-inactivating (I(K,f)) and delayed rectifying (I(K,dr)) components of the outward current were identified. I(K,f) was characterized by fast kinetics of current decay, negative steady-state activation and inactivation dependencies and sensitivity to 4-aminopyridine with an apparent K(d) of 0.32 mM, properties similar to those of the A-type K(+) current. In contrast, I(K,dr) activated and inactivated at more positive potentials. The time constant of activation of I(K,dr) was voltage dependent with an e-fold decrease per 21 mV depolarization. I(K,dr) was inhibited by clofilium, a blocker of voltage-gated K(+) channels, with an IC(50) of 12 micro M and was not blocked by 5 mM 4-aminopyridine. The possible significance of the voltage-gated currents is discussed.     

Ionic basis of the resting membrane potential and action potential in the pharyngeal muscle of Caenorhabditis elegans

The pharynx of C. elegans is a rhythmically active muscle that pumps bacteria into the gut of the nematode. This activity is maintained by action potentials, which qualitatively bear a resemblance to vertebrate cardiac action potentials. Here, the ionic basis of the resting membrane potential and pharyngeal action potential has been characterized using intracellular recording techniques. The resting membrane potential is largely determined by a K(+) permeability, and a ouabain-sensitive, electrogenic pump. As previously suggested, the action potential is at least partly dependent on voltage-gated Ca(2+) channels, as the amplitude was increased as extracellular Ca(2+) was increased, and decreased by L-type Ca(2+) channel blockers verapamil and nifedipine. Barium caused a marked prolongation of action potential duration, suggesting that a calcium-activated K(+) current may contribute to repolarization. Most notably, however, we found that action potentials were abolished in the absence of external Na(+). This may be due, at least in part, to a Na(+)-dependent pacemaker potential. In addition, the persistence of action potentials in nominally free Ca(2+), the inhibition by Na(+) channel blockers procaine and quinidine, and the increase in action potential frequency caused by veratridine, a toxin that alters activation of voltage-gated Na(+) channels, point to the involvement of a voltage-gated Na(+) current. Voltage-clamp analysis is required for detailed characterization of this current, and this is in progress. Nonetheless, these observations are quite surprising in view of the lack of any obvious candidate genes for voltage-gated Na(+) channels in the C. elegans genome. It would therefore be informative to re-evaluate the data from these homology searches, with the aim of identifying the gene(s) conferring this Na(+), quinidine, and veratridine sensitivity to the pharynx.     

Processing of influenza HA protein in MDCK cells: Components with different mobilities in polyacrylamide gel electrophoresis and their precursor-product relationships

Summary In influenza virus-infected MDCK cells labelled with¹⁴C-chlorella hydrolysate or³⁵S-methionine a virus-specific protein component is revealed migrating slightly faster than HA protein in polyacrylamide gel electrophoresis. Under chase conditions the component disappears either completely or partially, with a concomitant intensification of the HA band. The rate and extent of this transition are strain-dependent. Both the HA band and the faster moving component are not revealed if the cells are labelled in the presence of 20mM of D-glucosamine. In primary cell cultures of chick embryos a single HA band with a mobility similar to that of the faster moving component in MDCK cells has been observed. It is suggested that the transition of the label from the faster moving component to the HA band reflects the final step of HA processing specific for MDCK cells.With 7 Figures     

Muscle-epidermis interactions affect exoskeleton patterning in Caenorhabditis elegans.

The C. elegans hypodermis is a single epithelial cell layer separated from the musculature by a thin basement membrane on its basal surface. The hypodermis secretes the extracellular material of the cuticle from its apical surface. The regulation of cuticle synthesis and apical secretion is not well understood. UNC-95 is a component of the muscle dense bodies and M-lines, which are integrin-based adhesion complexes required for force transduction to the cuticle. Using gene expression profiling and in vivo assays, we show that, in unc-95 mutant worms, there is an increase in expression levels of a group of hypodermal and pharyngeal genes related to cuticle structure and molting. Moreover, the cuticle structure of unc-95 mutant adult is impaired. Our findings suggest that aberrant force transduction from the structurally impaired muscle attachments across the basement membrane to the underlying hypodermis elicits intercellular signaling that plays a role in regulating cuticle synthesis and patterning.