Breath sulfides and pulmonary function in cystic fibrosis.

We have determined the concentrations of carbonyl sulfide (OCS), dimethylsulfide, and carbon disulfide (CS(2)) in the breath of a group of cystic fibrosis (CF) patients and one of healthy controls. At the detection sensitivity in these experiments, room air always contained measurable quantities of these three gases. For each subject the inhaled room concentrations were subtracted from the time-coincident concentrations in exhaled breath air. The most significant differences between the CF and control cohorts in these breath-minus-room values were found for OCS. The control group demonstrated a net uptake of 250 +/- 20 parts-per-trillion-by-volume (pptv), whereas the CF cohort had a net uptake of 110 +/- 60 pptv (P = 0.00003). Three CF patients exhaled more OCS than they inhaled from the room. The OCS concentrations in the CF cohort were strongly correlated with pulmonary function. The dimethylsulfide concentrations in breath were greatly enhanced over ambient, but no significant difference was observed between the CF and healthy control groups. The net (breath minus room) CS(2) concentrations for individuals ranged between +180 and -100 pptv. They were slightly greater in the CF cohort (+26 +/- 38 pptv) vs. the control group (-17 +/- 15 pptv; P = 0.04). Lung disease in CF is accompanied by the subsistence of chronic bacterial infections. Sulfides are known to be produced by bacteria in various systems and were therefore the special target for this investigation. Our results suggest that breath sulfide content deserves attention as a noninvasive marker of respiratory colonization.

Mechanisms of synergistic cytokine-induced nitric oxide production in human alveolar epithelial cells.

Nitric oxide (NO) derived from inducible NO synthase (iNOS) at sites of inflammation is closely related to host defense against infection and airway inflammation. Cytokines are known to stimulate NO production in human alveolar epithelial cells in a synergistic (nonlinear or nonadditive) manner. The mechanism of this synergy is not known. We measured the activation of the transcription factor NF-kappaB, the iNOS protein, and NO production in A549 monolayers (human alveolar epithelial cell line) in response to different combinations of IL-1beta, INF-gamma, and TNF-alpha (100 ng/ml), and the cofactors FMN, FAD, and BH4. We found that both IL-1beta and TNF-alpha could independently activate cytosolic NF-kappaB, direct its translocation into the nucleus, and induce iNOS monomer synthesis. In addition, different combinations of cytokines produced synergistic amounts of iNOS monomers. Exogenous BH4 (0.1 microM) had no impact on NO production induced by cytokine combinations that included IL-1beta, but significantly enhanced NO production in the presence of INF-gamma and TNF-alpha, and allowed TNF-alpha independently to produce NO. We conclude that there are at least three mechanisms of synergistic cytokine-induced NO production: (1) the biosynthesis of iNOS monomer due to nonlinear interactions by transcription factors, (2) synergistic cytosolic activation of NF-kappaB, and (3) parallel biosynthesis of BH4 in the presence of cytokine combinations that include IL-1beta.

Distribution of somatic H1 subtypes is non-random on active vs. inactive chromatin II: distribution in human adult fibroblasts.

For nearly twenty years researchers have observed changes in the histone H1 subtype content of tissues as an organism develops into an adult. To better understand the consequences of such changes, immunofractionation of chromatin using previously characterized antibodies specific for human H1 subtypes was employed in the analysis of a fibroblast cell strain derived from a 37-year-old individual. DNAs isolated from immunoprecipitates were probed for the existence of a variety of DNA sequences. The results presented lend further support to a previously-proposed model (Parseghian et al. [2000] Chromosome Res 8:405-424) in which transcription of a sequence is accompanied by the selective depletion of subtypes. The data also suggest that there is more total H1 on actively transcribed sequences in these cells as compared to fetal fibroblasts and that there is less difference in the subtype compositions of active genes vs. inactive sequences in this strain. Specifically, the consequences of these changes appear to correlate with the attenuation of the heat shock response in aging fibroblasts. In a broader context, these results could explain why there are reductions in transcription in cells from mature tissue that approach senescence.

The distribution of somatic H1 subtypes is non-random on active vs. inactive chromatin: distribution in human fetal fibroblasts.

Chromatin immunoprecipitation was employed to determine whether or not the previously reported depletion of histone H1 on actively transcribed sequences was selective with respect to H1 subtypes. DNA of immunofractionated chromatin was analyzed by slot-blots for repetitive sequences and PCR for single and low-copy sequences. Based on the analysis of a diverse set of sequences, we report distinct differences in subtype distributions. Actively transcribed chromatin, as well as chromatin poised for transcription, is characterized by a relative depletion of somatic H1 subtypes 2 and 4 (H1s-2 and H1s-4),whereas facultative and constitutive heterochromatin contain all four somatic subtypes. These results support a model in which subtypes are selectively depleted upon gene expression. In turn, the data also support the possibility that the somatic subtypes have different functional roles based on their selective depletion from different classes of DNA sequences.

Music training causes long-term enhancement of preschool children's spatial-temporal reasoning.

Predictions from a structured cortical model led us to test the hypothesis that music training enhances young children's spatial-temporal reasoning. Seventy-eight preschool children participated in this study. Thirty-four children received private piano keyboard lessons, 20 children received private computer lessons, and 24 children provided other controls. Four standard, age-calibrated, spatial reasoning tests were given before and after training; one test assessed spatial-temporal reasoning and three tests assessed spatial recognition. Significant improvement on the spatial-temporal test was found for the keyboard group only. No group improved significantly on the spatial recognition tests. The magnitude of the spatial-temporal improvement from keyboard training was greater than one standard deviation of the standardized test and lasted at least one day, a duration traditionally classified as long term. This represents an increase in time by a factor of over 100 compared to a previous study in which listening to a Mozart piano sonata primed spatial-temporal reasoning in college students. This suggests that music training produces long-term modifications in underlying neural circuitry in regions not primarily concerned with music and might be investigated using EEG. We propose that an improvement of the magnitude reported may enhance the learning of standard curricula, such as mathematics and science, that draw heavily upon spatial-temporal reasoning.

A multifactorial study of patients with asthma. Part 2: air pollution, animal dander and asthma symptoms.

As part of a multifactorial computer-assisted study of patients with asthma, the relationship between air pollution, animal dander and asthma symptoms was evaluated. No association was found between four major air pollutants (carbon monoxide, ozone, nitrogen oxides and sulfur dioxide) and asthma symptoms. Patients who owned cats and dogs reported more severe asthma symptoms (p less than .01) than patients who did not own cats and dogs. The evaluations completed to date indicate that daily exposure to cats and dogs accounts for more of the asthma symptoms differences between patients than daily exposure to air pollutants.