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Biomedical subjects

P Phelan

Publications and source records attributed to P Phelan.

At least 19 recordsLinked to original sources
PubMed2006

Paramagnetic particles and mixing in micro-scale flows.

Mixing in microscale flows with rotating chains of paramagnetic particles can be enhanced by adjusting the ratio of viscous to magnetic forces so that chains dynamically break and reform. Lattice Boltzmann (LB) simulations were used to calculate the interaction between the fluid and suspended paramagnetic particles under the influence of a rotating magnetic field. Fluid velocities obtained from the LB simulations are used to solve the advection diffusion equation for massless tracer particles. At relatively high Mason numbers, small chains result in low edge velocities, and hence mixing is slower than at other Mason numbers. At low Mason numbers, long, stable chains form and produce little mixing toward the center of the chains. A peak in mixing rate is observed when chains break and reform. The uniformity of mixing is greater at higher Mason numbers because more small chains result in a larger number of small mixing areas.

Algorithms↗
PubMed2001

Innexins get into the gap.

Connexins were first identified in the 1970s as the molecular components of vertebrate gap junctions. Since then a large literature has accumulated on the cell and molecular biology of this multi-gene family culminating recently in the findings that connexin mutations are implicated in a variety of human diseases. Over two decades, the terms "connexin" and "gap junction" had become almost synonymous. In the last few years a second family of gap-junction genes, the innexins, has emerged. These have been shown to form intercellular channels in genetically tractable invertebrate organisms such as Drosophila melanogaster and Caenorhabditis elegans. The completed genomic sequences for the fly and worm allow identification of the full complement of innexin genes in these two organisms and provide valuable resources for genetic analyses of gap junction function.

Animals↗
PubMed2000

Two Drosophila innexins are expressed in overlapping domains and cooperate to form gap-junction channels.

Members of the innexin protein family are structural components of invertebrate gap junctions and are analogous to vertebrate connexins. Here we investigate two Drosophila innexin genes, Dm-inx2 and Dm-inx3 and show that they are expressed in overlapping domains throughout embryogenesis, most notably in epidermal cells bordering each segment. We also explore the gap-junction-forming capabilities of the encoded proteins. In paired Xenopus oocytes, the injection of Dm-inx2 mRNA results in the formation of voltage-sensitive channels in only approximately 40% of cell pairs. In contrast, Dm-Inx3 never forms channels. Crucially, when both mRNAs are coexpressed, functional channels are formed reliably, and the electrophysiological properties of these channels distinguish them from those formed by Dm-Inx2 alone. We relate these in vitro data to in vivo studies. Ectopic expression of Dm-inx2 in vivo has limited effects on the viability of Drosophila, and animals ectopically expressing Dm-inx3 are unaffected. However, ectopic expression of both transcripts together severely reduces viability, presumably because of the formation of inappropriate gap junctions. We conclude that Dm-Inx2 and Dm-Inx3, which are expressed in overlapping domains during embryogenesis, can form oligomeric gap-junction channels.

Amino Acid Sequence↗
PubMed1999

Psychosocial predictors of adherence to nutritional recommendations and growth outcomes in children with cystic fibrosis.

This study aimed to elucidate the relationship between maternal psychosocial factors related to dietary adherence and growth outcomes in their children with cystic fibrosis (CF). Twenty-five children with CF and mild lung disease, aged 7-12 years, were weighed and measured and completed detailed food records. Mothers completed questionnaires that measured general nutritional knowledge, nutritional knowledge specific to CF, coping strategies, dieting behaviors, self-efficacy about the ability to provide the correct diet, and attitudes and beliefs about CF. Of the cohort, only 16% adhered to the dietary recommendations. Dietary adherence was positively correlated with weight. Maternal nutritional knowledge specific to CF significantly predicted children's dietary adherence score. There was a significant negative correlation between the child's weight and mothers who were dieting successfully. Other psychosocial factors assessed were not related to dietary adherence. Improving the mother's knowledge about nutritional needs in CF appears worthwhile and may have an impact on growth.

Adult↗
PubMed1999

Physiological and psychosocial contributors to malnutrition in children with cystic fibrosis: review.

Malnutrition was once thought to be an inevitable consequence of cystic fibrosis (CF). It is now considered preventable but still contributes considerable morbidity in children. Malnutrition is linked to poorer pulmonary function, reduced survival and quality of life. As the anticipated lifespan of children with CF continues to lengthen, the prevention of malnutrition attains greater importance. This review explores the complex organic and psychosocial factors implicated in the aetiology of malnutrition associated with CF.

Child↗
PubMed1998

Drosophila Shaking-B protein forms gap junctions in paired Xenopus oocytes.

In most multicellular organisms direct cell-cell communication is mediated by the intercellular channels of gap junctions. These channels allow the exchange of ions and molecules that are believed to be essential for cell signalling during development and in some differentiated tissues. Proteins called connexins, which are products of a multigene family, are the structural components of vertebrate gap junctions. Surprisingly, molecular homologues of the connexins have not been described in any invertebrate. A separate gene family, which includes the Drosophila genes shaking-B and l(1)ogre, and the Caenorhabditis elegans genes unc-7 and eat-5, encodes transmembrane proteins with a predicted structure similar to that of the connexins. shaking-B and eat-5 are required for the formation of functional gap junctions. To test directly whether Shaking-B is a channel protein, we expressed it in paired Xenopus oocytes. Here we show that Shaking-B localizes to the membrane, and that its presence induces the formation of functional intercellular channels. To our knowledge, this is the first structural component of an invertebrate gap junction to be characterized.

Animals↗
PubMed1998

Current approaches to the nutritional management of cystic fibrosis in Australia.

OBJECTIVE: The aim of this study was to determine current Australian practice for the nutritional management of cystic fibrosis (CF) and compare it to USA and UK guidelines. METHODOLOGY: A structured questionnaire was completed by dietitians from 15 major CF centres. It was estimated that these centres manage or co-manage 84% of Australians with CF. RESULTS: There was close agreement between UK and USA guidelines and Australian practice for dietary intervention strategies, nutritional monitoring and surveillance, and electrolyte replacement. Infant feeding practices were more closely aligned with the UK. There were some differences in the areas of pancreatic enzyme replacement therapy, vitamin requirements in CF and dietary management of CF-related diabetes. CONCLUSIONS: Despite the lack of formal agreement, nutritional management practices of most Australian centres are closely aligned with current published international recommendations. However, there is need for consensus in the area of enzyme replacement therapy, management of CF-related diabetes and vitamin supplementation based on optimal clinical outcomes.

Australia↗
PubMed1998

Relation between dietary intake and nutritional status in cystic fibrosis.

This study evaluated adherence to current dietary recommendations of children with cystic fibrosis and mild lung disease and their siblings by comparing energy intake. Fifty children (25 with cystic fibrosis) aged between 7 and 12 years completed the study. Energy intake was assessed by weighed dietary intake, resting energy expenditure was used to calculate recommended daily intakes. The children with cystic fibrosis had significant deficits in Z scores for both height and weight compared with their siblings, but there was no difference in percentage of ideal weight for height. The cystic fibrosis group had a significantly higher energy intake per kilogram body weight per day but there was no difference in the percentage of energy derived from fat, protein or carbohydrate. Energy intake (per kg/day) and fat intake (g/kg) were both significant predictors of weight for height in the cystic fibrosis group. Targets for dietary management in cystic fibrosis should perhaps be related to fat intake per kilogram body weight.

Body Height↗
PubMed1998

Elemental content of airway surface liquid from infants with cystic fibrosis.

We tested the hypothesis that airway surface liquid (ASL) electrolyte composition is altered in infants with cystic fibrosis (CF) and that the presence of airway inflammation affects ASL composition. We measured the tracheal ASL sodium and chloride concentration and examined bronchoalveolar lavage (BAL) fluid cytology, interleukin-8 (IL-8) concentrations, and quantitative bacterial culture in 19 infants and young children with CF. Seven infants undergoing bronchoscopy for the evaluation of stridor served as non-CF controls. In addition, we measured nasal ASL sodium and chloride concentrations from 10 young adults with CF and from 10 control subjects. On the basis of the BAL findings, the infants with CF were divided into three groups: one with little evidence of pulmonary inflammation (CF-NI, n = 5); one with obvious pulmonary inflammation (CF-I, n = 7); and an intermediate group (CF-MI, n = 7). We found the ASL sodium was not different among any of the four groups (means mM +/- SE, 85 +/- 10 controls; 78 +/- 16 CF-NI; 83 +/- 9 CF-MI, 84 +/- 9 CF-I). In contrast the ASL chloride was lower in the CF-NI group when compared with control subjects (108 +/- 5 control subjects; 77 +/- 7 CF-NI, p < 0.01). In the CF-I and CF-MI groups, the ASL chloride concentrations were of intermediate values (CF-I 95 +/- 10 mM; CF-MI 96 +/- 9 mM) and not significantly different from controls. Results from the nasal ASL analysis showed no significant differences in sodium and chloride concentrations in the CF group compared with control subjects. These results suggest that the primary abnormality of ASL composition is a reduction in chloride concentration. ASL composition appears to be affected by the presence of airway inflammation.

Adolescent↗
PubMed1997

Pulmonary oxidative stress response in young children with cystic fibrosis.

BACKGROUND: It has been suggested that oxidative stress contributes to lung injury in cystic fibrosis. There is, however, no direct evidence of increased pulmonary oxidative stress in cystic fibrosis nor of the effects of inflammation on the major pulmonary antioxidant, glutathione. A study was undertaken to measure these parameters in infants and young children in the presence or absence of pulmonary inflammation. METHODS: Thirty two infants and young children with cystic fibrosis of mean (SD) age 21.4 (15.3) months (range 2-54) and seven non-cystic fibrosis control subjects of mean (SD) age 21.0 (21.2) months (range 2-54) were studied using bronchoalveolar lavage (BAL). On the basis of the BAL findings the cystic fibrosis group was divided into those with (CF-I) and those without pulmonary inflammation (CF-NI). Levels of lipid hydroperoxide, total glutathione, and gamma-glutamyl transpeptidase (gamma-GT) were then measured in the BAL fluid. RESULTS: The concentrations of lipid hydroperoxide and gamma-GT in the epithelial lining fluid were significantly increased in the CF-I group compared with the control and CF-NI groups, each of which had similar values for these parameters (ratio of geometric means for CF-I group versus control for lipid hydroperoxide 5.4 (95% confidence interval (CI) 1.8 to 15.8) and for gamma-GT 5.2 (95% CI 1.4 to 19.4)). The glutathione concentration tended to be lower in the CF-I subjects but the difference did not reach statistical significance. CONCLUSIONS: These results demonstrate that the airways in patients with cystic fibrosis are exposed to increased oxidative stress which appears to be a consequence of pulmonary inflammation rather than part of the primary cystic fibrosis defect. The increase in gamma-GT in the CF-I group suggests a mechanism by which extracellular glutathione could be utilised by airway epithelial cells.

Bronchoalveolar Lavage Fluid↗
PubMed1997

Surfactant composition in infants and young children with cystic fibrosis.

We tested the hypothesis that the composition of bronchial surfactant is normal in infants with cystic fibrosis (CF) in the absence of active lung disease but that it is altered by lower respiratory tract infection and inflammation. We examined the total phospholipid (PL), disaturated phospholipid (DSP), surfactant protein-A (SP-A), surfactant protein B (SP-B), and surface activity in bronchoalveolar lavage fluid from 27 subjects with CF whose mean age was 22.7 (SD 14.5) mo. Six infants with stridor served as non-CF controls. Twelve of the subjects with CF (CF-I group) had evidence of active pulmonary infection or inflammation which was absent in the remaining 15 subjects (CF-NI group). We found no differences in the surfactant composition or activity between controls and the CF-NI group. In contrast, the DSP/PL ratio was lower in the CF-I subjects than in both the CF-NI subjects (p = 0.05) and controls (p < 0.01) suggesting a disturbance of surfactant function. SP-A concentrations were higher in the CF-I group compared to the other two groups (p < 0.05). These results suggest that the bronchial surfactant of infants with CF is altered following lower airway infection and inflammation and is not a primary abnormality associated with this disorder.

Bronchoalveolar Lavage Fluid↗
PubMed1996

Mutations in shaking-B prevent electrical synapse formation in the Drosophila giant fiber system.

The giant fiber system (GFS) is a simple network of neurons that mediates visually elicited escape behavior in Drosophila. The giant fiber (GF), the major component of the system, is a large, descending interneuron that relays visual stimuli to the motoneurons that innervate the tergotrochanteral jump muscle (TTM) and dorsal longitudinal flight muscles (DLMs). Mutations in the neural transcript from the shaking-B locus abolish the behavioral response by disrupting transmission at some electrical synapses in the GFS. This study focuses on the role of the gene in the development of the synaptic connections. Using an enhancer-trap line that expresses lacZ in the GFs, we show that the neurons develop during the first 30 hr of metamorphosis. Within the next 15 hr, they begin to form electrical synapses, as indicated by the transfer of intracellularly injected Lucifer yellow. The GFs dye-couple to the TTM motoneuron between 30 and 45 hr of metamorphosis, to the peripherally synapsing interneuron that drives the DLM motoneurons at approximately 48 hr, and to giant commissural interneurons in the brain at approximately 55 hr. Immunocytochemistry with shaking-B peptide antisera demonstrates that the expression of shaking-B protein in the region of GFS synapses coincides temporally with the onset of synaptogenesis; expression persists thereafter. The mutation shak-B2, which eliminates protein expression, prevents the establishment of dye coupling shaking-B, therefore, is essential for the assembly and/or maintenance of functional gap junctions at electrical synapses in the GFS.

Amino Acid Sequence↗
PubMed1995

Effect of magnetic field strength on the linewidth and spin-lattice relaxation time of the thiocyanate carbon of cyanylated beta-lactoglobulin B: optimization of the experimental parameters for observing thiocyanate carbons in proteins.

The linewidths and spin-lattice relaxation times of the 13C-n.m.r. signal at 109.7 p.p.m. due to the thiocyanate carbon of intact [cyanato-13C]cyanylated-beta-lactoglobulin-B have been determined at magnetic field strengths of 1.88, 6.34 and 11.74 T as well as the spin-lattice relaxation times of its backbone alpha-carbon atoms. The linewidths were directly proportional to the square of the magnetic field strength and we conclude that, at magnetic field strengths of 6.34 T or above, more than 70% of the linewidth will be determined by chemical-shift anisotropy. We estimate that the spin-lattice relaxation time resulting from the chemical-shift anisotropy of the thiocyanate carbon is 1.52 +/- 0.1 s and we conclude that for magnetic field strengths of 6.34 T and above the observed spin-lattice relaxation time of the thiocyanate carbon will be essentially independent of magnetic field strength. Using the rigid-rotor model we obtain estimates of the rotational correlation time of [cyanato-13C]cyanylated-beta-lactoglobulin-B and of the chemical-shift anisotropy shielding tensor of its thiocyanate carbon. We have calculated the linewidths and spin-lattice relaxation times of thiocyanate carbons at magnetic field strengths of 1.88-14.1 T in proteins with M(r) values in the range 10,000-400,000. The effects of magnetic field strength on the resolution and signal-to-noise ratios of the signals due to thiocyanate carbons attached to proteins of M(r) greater than 10,000 are discussed.

Carbon↗
PubMed1995

Gender differences in lung growth.

Annual measurements of lung volumes and forced expiratory flows were made in 281 boys and girls from 8 to 12 years and in another cohort of 287 from 12 to 20 years to measure longitudinal lung growth. Gender differences in growth of lung function were documented, with girls generating greater volume-standardized maximal expiratory flows until age 18.5 years. Beyond that age boys generated higher expiratory flows in proportion to total lung capacity (TLC). There was a time lag of up to 1 year between the age of peak growth velocity in lung volume and peak growth velocity in height. Age at peak growth in flow lagged another year behind that in volume. This was noted more in boys than girls. Dysanaptic lung growth was found with differing rates of growth of maximal expiratory flow compared with TLC or vital capacity (VC).

Adolescent↗
PubMed1995

Incest and its meaning: the perspectives of fathers and daughters.

This article describes incestuous events and the structure of meaning surrounding the events by biologic fathers and stepfathers and biologic daughters and stepdaughters. Using a symbolic interaction framework the study is guided by the thesis that the meanings people attach to incestuous events are central to understanding the phenomena of incest. Data were obtained from indepth interviews with 40 men (14 natural fathers and 26 stepfathers) and 44 children (18 biologic daughters and 26 stepdaughters). The interviews emphasized fathers' and daughters' recollection of events and their thoughts and interpretations of the incestuous activity while it was occurring. Both fathers and daughters reported that the sexual activity grew out of already existing family interactions. However, fathers and daughters' cognitions surrounding the events differed dramatically. Many of the fathers said their thoughts were dominated by themes of sexual gratification, control, power and anger, and rights and responsibilities vis-à-vis their role as father or stepfather. Daughters reported disbelief, confusion, guilt, and anger. According to fathers, they completely misread their child's reaction to what was happening. Although fathers said that they knew what they were doing was wrong, few reported that they were concerned with possible legal consequences.

Adolescent↗