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Biomedical subjects

L Nixon

Publications and source records attributed to L Nixon.

9 recordsLinked to original sources

Pulmonary function, serum markers of inflammation, and IgG antibodies to core lipopolysaccharide of Burkholderia cepacia in adults with cystic fibrosis, following colonization with Burkholderia cepacia.

Eight patients with cystic fibrosis [CF] colonized with Pseudomonas aeruginosa (P. aeruginosa) had serial lung function, peripheral blood inflammatory markers, and serum IgG antibodies to Burkholderia cepacia (B. cepacia) lipopolysaccharide measured in the months preceding and following colonisation with B. cepacia. One patient experienced a fall in FEV(1) from 33% to 19% of predicted values, coinciding with the first sputum isolation of B. cepacia, and he died 12 weeks later. He had a rise in inflammatory markers preterminally, and this change was refractory to antibiotic therapy. There was no significant fall in FEV(1) % of predicted values in the remaining seven patients, and no significant changes in their serum markers of inflammation following colonization with B. cepacia over a median (range) period of 10.9 (7.3-12.0) months.

Adult↗

IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis.

The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators. Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -70 degrees C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity. In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0-153) versus 0 (0-5.6) ng x mL(-1)) HNE (136 (32-694) versus 14 (0-516) ng x mL(-1)) and elastase activity (4 (1-220) versus 1 (0-339) mU x mL(-1)) were found. These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease.

Acute Disease↗

Cystic fibrosis: inflammatory response to infection with Burkholderia cepacia and Pseudomonas aeruginosa.

Pulmonary colonization by Burkholderia cepacia in cystic fibrosis (CF) may be associated with enhanced deterioration of pulmonary function. This may be due to a more florid host inflammatory response than in colonization by Pseudomonas aeruginosa, leading to greater lung injury. Circulating markers of inflammation were determined during infective exacerbations and periods of clinical stability in an 18 month prospective study in adults with CF colonized by P. aeruginosa (n=41). B. cepacia (n=13) and in adults who intermittently grew B. cepacia (n=6). There were no differences between the levels of the inflammation markers measured in the three groups (P. aeruginosa, B. cepacia, B. cepacia intermittent) at any of the assessment points. When clinically stable, levels of inflammatory markers in all groups were elevated compared to a matched non-CF population, indicating, continuous inflammation and the potential for lung damage between infective exacerbations. This study does not support the hypothesis that pulmonary colonization with Burkholderia cepacia is associated with a heightened inflammatory response compared with Pseudomonas aeruginosa colonization.

Adult↗

Identification of Asp95 as the site of succinimide formation in recombinant human glial cell line-derived neurotrophic factor.

Human glial cell line-derived neurotrophic factor is a single polypeptide of 134 amino acids and functions as a disulfide-linked dimer. Incubation of the protein in pH 5.0 and at 37 degreesC for 1 week showed that 5% of the material was converted to a form that eluted after the major protein peak on a cation-exchange column. The modified component gave an average molecular mass of 30367.0 u (theoretical = 30384.8 u). Within measurement error, this 17.8-u decrease in mass indicated the loss of a water molecule. This observation, together with the protein's behavior on cation-exchange chromatography and the mode of incubation used to generate the modification, was consistent with cyclic imide (succinimide) formation at an aspartyl residue. Hence, only a monomer of the dimeric protein was modified. The modified monomer was purified and subjected to peptic degradation. By a combination of N-terminal analysis and mass spectrometry, the region containing Asp95-Lys96 was identified to be modified. This was further confirmed by carboxypeptidase Y digestion of the modified peptide where the modified region was found to be resistant to further enzymatic degradation. Furthermore, incubation of the modified monomer in pH 8. 5 for 2 h yielded two peaks, in agreement with the succinimide model where the cyclic imide was hydrolyzed into a mixture of isoaspartate and aspartate. Tryptic mapping of the isoaspartyl-containing protein showed that Asp95 was refractory to Edman degradation, confirming it was in the isoaspartate form. Hence, the modification observed was due to succinimide formation at Asp95. This is the first report of succinimide formation at an Asp-Lys linkage.

Amino Acid Sequence↗

The effects of magnetic stabilization on the structure and performance of liquid fluidized beds.

Liquid fluidized beds containing porous magnetic ion-exchange particles with densities ca. 1.03-1.16 g mL-1 were examined. The effect of magnetic stabilization was studied, both in terms of bed physical characteristics and sorptive behavior. Maximum applied magnetic field strength was approximately 200 oersted. Breakthrough and pulse analyses were carried out with protein and acetone solutions, respectively, with liquid flow rates ranging from approximately 1 to 3 cm min-1. Acetone pulses in columns containing 7 mL of particles had plate numbers ranging from 2.5 to 18 for magnetically stabilized beds and from 7.8 to 20 for non-stabilized fluidized beds. Under any particular set of conditions, magnetic stabilization always resulted in poorer efficiency, both in pulse analyses and in protein breakthrough experiments.

Adsorption↗

Transposon-induced non-motile mutants of Vibrio cholerae.

Non-motile mutants of Vibrio cholerae were isolated after transposon insertion mutagenesis with either Tn5 on a plasmid or Tn10ptac mini-kan in bacteriophage lambda. The physical location and number of transposon insertions was determined. Eighteen Tn5 insertion mutants and 11 Tn10ptac mini-kan insertion mutants had single unique insertion sites. The 18 Tn5 insertions were contained within six different EcoRI fragments and the 11 Tn10ptac mini-kan insertions were contained within eight different fragments of V. cholerae chromosomal DNA. These data suggest that multiple genes are involved in motility. Immunoblot analysis of non-motile mutants with antibody to wild-type flagellar core protein indicated that two of the non-motile mutants made flagellar core protein. Three additional mutants reacted weakly with the antibodies. However, these mutants with immunopositive reactions did not produce any structures which resembled flagella by transmission electron microscopy. In addition, none of the other non-motile mutants produced wild-type flagella. However, five mutants which did not react in the immunoblot produced a structure which resembled a flagellar sheath without the internal flagellar core. In addition to having no filamentous core, the sheaths often extended from the sides of the bacteria, rather than from the poles where the flagellum is normally located. The data suggest that sheath formation is independent of flagellar filament formation, but that proper positioning of the sheath may require the flagellar filament.

DNA Transposable Elements↗