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Biomedical subjects

S Phelps

Publications and source records attributed to S Phelps.

16 recordsLinked to original sources
PubMed2005

Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population.

BACKGROUND: The cysteinyl-leukotrienes (cys-LTs) are important pro-inflammatory mediators in asthma, and have been shown to have a role in specific disease subtypes, including asthma severity. Few studies have investigated the role of polymorphisms in the ALOX5AP gene, encoding 5-lipoxygenase activating protein (FLAP), and asthma. We hypothesized that polymorphisms in this gene are associated with asthma and in particular, with asthma severity, in an Australian population. OBJECTIVE: To screen the coding region of the ALOX5AP gene for polymorphisms and to determine the association between previously described polymorphisms and asthma and asthma severity in an Australian population. METHODS: We used PCR-SSCP and PCR-RFLP analysis to examine a previously described promoter polyA variable repeat polymorphism and two intronic polymorphisms (IVS2+12C>A, IVS2+105T>C), and to screen all five exons of the gene for new polymorphisms, in a large Australian population of randomly selected, non-asthmatic controls (n=457), mild asthmatics (n=274), moderate asthmatics (n=231) and severe asthmatics (n=79). RESULTS: We confirmed the presence of two polymorphisms in intron 2 and found no association between these polymorphisms and asthma or asthma severity, nor between a promoter polymorphism in the ALOX5AP gene and asthma or asthma severity. Gene fragment analysis of the promoter polymorphism revealed novel, conserved repeat numbers in our population, and no new polymorphisms were found in the coding region of the gene. CONCLUSION: These findings in a large, well characterized asthma population, reveal that, while FLAP is an important enzyme in cys-LTs biosynthesis, polymorphisms in the ALOX5AP gene are not likely to be functionally associated with the asthma phenotype.

5-Lipoxygenase-Activating Proteins↗
PubMed2004

Urinary leukotriene E4 and 9 alpha, 11 beta-prostaglandin F concentrations in mild, moderate and severe asthma, and in healthy subjects.

BACKGROUND: Airway inflammation in asthma is associated with cysteinyl leukotriene and prostaglandin D(2) production. Measurement of urinary metabolites of these eicosanoids may be useful for monitoring asthma patients. However, the influence of asthma phenotype and severity on basal urinary excretion of these metabolites is unknown. OBJECTIVE: To compare urinary leukotriene (LT)E(4) and 9 alpha, 11 beta-prostaglandin (PG)F(2) concentrations in large groups of mild, moderate and severe asthmatic patients and healthy control subjects. METHODS: Asthma severity, treatment and aspirin sensitivity were assessed by questionnaire in 168 asthmatic patients. Basal LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations were measured in urine samples from these patients and from 175 control subjects using enzyme immunoassays. RESULTS: Urinary LTE(4) was correlated with 9 alpha, 11 beta-PGF(2) in both control subjects and asthmatic patients (P<0.002). Median LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations in patients with severe asthma were significantly reduced compared with mild asthmatic patients (P<0.05 and <0.001, respectively). Urinary 9 alpha, 11 beta-PGF(2), but not LTE(4) was lower in asthmatic patients using inhaled corticosteroids (P<0.02). Multiple regression analysis indicated that urinary 9 alpha, 11 beta-PGF(2) concentration was negatively correlated with asthma severity (P=0.003) and also with % predicted FEV(1) (forced expiratory volume in 1 s) (P=0.005). CONCLUSIONS: Baseline urinary LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations are of limited value in discriminating between patients with different severities of asthma. Reduced urinary LTE(4) and 9 alpha, 11 beta-PGF(2) in patients with severe asthma suggest that direct or indirect effects of high-dose corticosteroid therapy combined with other factors associated with severe asthma may influence eicosanoid production. However, the negative association of urinary 9 alpha, 11 beta-PGF(2) with lung function suggests an adverse effect of chronic PGD(2) production on lung function in asthma, irrespective of severity.

Adult↗
PubMed1999

Interactions between beta 2-syntrophin and a family of microtubule-associated serine/threonine kinases.

A screen for proteins that interact with beta 2-syntrophin led to the isolation of MAST205 (microtubule-associated serine/threonine kinase-205 kD) and a newly identified homologue, SAST (syntrophin-associated serine/threonine kinase). Binding studies showed that beta 2-syntrophin and MAST205/SAST associated via a PDZ-PDZ domain interaction. MAST205 colocalized with beta 2-syntrophin and utrophin at neuromuscular junctions. SAST colocalized with syntrophin in cerebral vasculature, spermatic acrosomes and neuronal processes. SAST and syntrophin were highly associated with purified microtubules and microtubule-associated proteins, whereas utrophin and dystrophin were only partially associated with microtubules. Our data suggest that MAST205 and SAST link the dystrophin/utrophin network with microtubule filaments via the syntrophins.

Amino Acid Sequence↗
PubMed1998

Bolus intravenous infusion of amino acids or lipids does not stimulate gallbladder contraction in neonates on total parenteral nutrition.

BACKGROUND/PURPOSE: Stimulation of gallbladder contraction in patients receiving total parenteral nutrition (TPN) may be beneficial in preventing cholestatic jaundice associated with TPN. Bolus intravenous administration of either amino acids or fat promotes gallbladder contraction in normal adult volunteers after a period of starvation. This phenomenon has not been investigated in patients receiving continuous TPN. The aim of this study was to test the hypothesis that bolus intravenous infusion of amino acids or fat produces gallbladder contraction in neonates receiving TPN. METHODS: Twenty-eight studies of gallbladder contraction were performed in 18 neonates receiving continuous TPN (median weight, 2.3 kg; range, 1.3 to 7.3; gestational age, 37 weeks; range, 28 to 40; age, 6.5 days; range, 2 to 180). Different types of experiments were performed: (1) bolus intravenous infusion of amino acid or fat for 60 minutes at twice the normal infusion rate; (2) bolus intravenous infusion of amino acid or fat for 15 minutes at four times the normal infusion rate. Gallbladder volume was measured by real-time ultrasonography by a single investigator. Measurements were made before starting the bolus infusion and every 15 minutes for 1 hour. RESULTS: The volume of the gallbladder before bolus intravenous infusion was not significantly different between experiments (median, 985; range, 603 to 1,802 mm3). These volumes are consistent with an enlarged and atonic gallbladder as previously reported in infants receiving parenteral nutrition. In all experiments there was no significant decrease in gallbladder volume after bolus infusion of either amino acids or fat. CONCLUSIONS: Contrary to their effects in adults, bolus infusions of amino acids or fat did not induce gallbladder contraction in neonates on TPN. This may have been because of lack of starvation in the neonates and/or the effect of continuous glucose infusion.

Amino Acids↗
PubMed1998

Expression of full-length utrophin prevents muscular dystrophy in mdx mice.

Duchenne muscular dystrophy (DMD) is a lethal, progressive muscle wasting disease caused by a loss of sarcolemmal bound dystrophin, which results in the death of the muscle fiber leading to the gradual depletion of skeletal muscle. The molecular structure of dystrophin is very similar to that of the related protein utrophin. Utrophin is found in all tissues and is confined to the neuromuscular and myotendinous junctions in mature muscle. Sarcolemmal localization of a truncated utrophin transgene in the dystrophin-deficient mdx mouse significantly improves the dystrophic muscle phenotype. Therefore, up-regulation of utrophin by drug therapy is a plausible therapeutic approach in the treatment of DMD. Here we demonstrate that expression of full-length utrophin in mdx mice prevents the development of muscular dystrophy. We assessed muscle morphology, fiber regeneration and mechanical properties (force development and resistance to stretch) of mdx and transgenic mdx skeletal and diaphragm muscle. The utrophin levels required in muscle are significantly less than the normal endogenous utrophin levels seen in lung and kidney, and we provide evidence that the pathology depends on the amount of utrophin expression. These results also have important implications for DMD therapies in which utrophin replacement is achieved by delivery using exogenous vectors.

Animals↗
PubMed1997

Prenatal ultrasound diagnosis of gastrointestinal malformations.

Prenatal ultrasonography is commonly used to detect fetal structural abnormalities. The aim of this study was to evaluate the reliability of fetal sonography in the detection of congenital gastrointestinal malformations (GIM). From a prospective database of all major structural fetal anomalies detected by ultrasound over 3 years in a region with a population of 3.5 million and an annual birth rate of 52,000, 294 reports of GIM were identified and reviewed. There were 220 confirmed cases of GIM, of which only 35 (16%) had been correctly identified prenatally. Of 84 prenatal diagnoses of GIM, only 35 (42%) were confirmed postnatally. Prenatal ultrasound was most reliable in the detection of duodenal obstruction (55% confirmed cases identified prenatally) and least reliable in malformations of the hindgut. Of 44 cases of nonspecific sonographic bowel abnormality (eg, echogenic bowel) with adequate follow-up, only 12 (27%) had a confirmed GIM after delivery. This study demonstrates that the prenatal ultrasound scan is still unreliable in the detection or exclusion of fetal GIM, and consequently clinicians involved in prenatal sonography or counselling should exercise caution in making such diagnoses.

Digestive System Abnormalities↗
PubMed1997

Morbidity after neonatal inguinal herniotomy.

Neonatal inguinal herniotomy is recognised by paediatric surgeons to be a potentially difficult procedure. This study reviewed the clinical, operative, and outcome details of 74 infants undergoing herniotomy at less than 44 weeks' gestation with particular reference to the incidence of complications such as recurrent hernia and testicular atrophy. Follow-up information was obtained in 69 patients (93%, mean follow-up, 8.1 months). There were 8 recurrent hernias in 5 patients (2 bilateral recurrences, 1 second recurrence) giving an overall hernia recurrence rate of 8.6%. There was only 1 case of testicular atrophy (secondary to a wound infection and scrotal abscess). Despite the provision of a consultant-led service, the recurrence rate in neonates is much higher than that seen in the paediatric population as a whole. In light of commissioners' current demands for quality standards and managed healthcare, it is important that outcomes in this high-risk group are defined separately from those of other patients undergoing inguinal herniotomy.

Female↗
PubMed1997

Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice.

Dystrophin-deficient mice (mdx) expressing a truncated (trc) utrophin transgene show amelioration of the dystrophic phenotype. Here we report a multifunctional study demonstrating that trcutrophin expression leads to major improvements of the mechanical performance of muscle (that is, force development, mechanical resistance to forced lengthenings and maximal spontaneous activity) and of the maintenance of the intracellular calcium homeostasis. These are two essential functions of muscle fibers, known to be impaired in mdx mouse muscles and Duchenne muscular dystrophy (DMD) patients. Our results bring strong support to the hypothesis that muscle wasting in dystrophin-deficient DMD patients could be prevented by upregulation of utrophin.

Animals↗
PubMed1996

Epidemiology of firearm mortality and injury estimates: state of Connecticut, 1988-1993.

STUDY OBJECTIVES: To retrospectively determine the 6-year cumulative incidence rate of firearm mortality and estimate nonfatal firearm injuries in Connecticut. METHODS: Retrospective analysis of data originating from the Connecticut State Medical Examiner's Office and records from the Trauma Registry of one urban hospital. RESULTS: From January 1988 through December 1993, 1,625 Connecticut residents died from firearm-related injuries. The cumulative incidence rate was 49.4 deaths per 100,000 population during the 6-year study period. Rates peaked among 20- to 24-year-olds at 18.1 deaths per 100,000. Males outnumbered females more than eightfold. The ratio of nonfatal firearm injuries to firearm deaths was 7:1 for those shot by another, self-inflicted injuries were fatal in half of all cases. CONCLUSION: Analysis of firearm mortality data indicated that males in younger age categories were disproportionately affected. These rates combined with nonfatal injury projections demonstrate that firearms represent a significant public health threat to the population of Connecticut, reaching epidemic proportions among specific subpopulations. These results are consistent with those obtained from national studies.

Adolescent↗
PubMed1993

Garlic supplementation and lipoprotein oxidation susceptibility.

Interventions which make serum lipoproteins less susceptible to oxidation may be antiatherogenic. The antioxidant properties of garlic which have been demonstrated in vitro led us to investigate the effects of garlic supplements on lipoprotein oxidation susceptibility in humans. Ten healthy volunteers were given 600 mg/d of garlic powder (6 tablets of Kwai) for two weeks in a placebo-controlled, randomized, double-blind crossover trial. We found that although serum lipid and lipoprotein levels were not lowered in this short time period, the ex vivo susceptibility of apolipoprotein B-containing lipoproteins to oxidation was significantly decreased (-34%). Because garlic has been reported to beneficially affect serum lipid levels, platelet function, fibrinolysis and blood pressure, this additional effect of retarding lipoprotein oxidation may contribute to the potential antiatherosclerotic effect of garlic.

Adult↗
PubMed1991

Changes to synaptic ultrastructure in field CA1 of the rat hippocampus following intracerebroventricular injection of kainic acid.

To assess the nature and extent of ultrastructural damage due to low unilateral intracerebroventricular doses of kainic acid, treated rats were killed at survival times from 8 h to 14 weeks. Degenerative changes in field CA1 of the hippocampus included dark profiles (often presynaptic), lucent areas enveloping axonic or dendritic elements, damaged myelin sheaths, and enlarged glial profiles. The effect of kainic acid ipsilaterally was maximal at three days but also apparent up to 14 weeks. Contralateral CA1 showed similar though less extensive abnormalities. These observations suggest that, despite rapid synaptic replacement (Nadler et al., Brain Res. 191, 387-403, 1980), long-term electrophysiological abnormalities (Cornish and Wheal, Neuroscience 28, 563-571, 1989) may stem not only from inappropriate reactive synaptogenesis but also from a continuing state of neuronal degeneration.

Animals↗