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Biomedical subjects

J Bryan

Publications and source records attributed to J Bryan.

At least 19 recordsLinked to original sources
PubMed2006

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Adolescent↗
PubMed2006

Rapid onset of effect of sodium alginate on gastro-oesophageal reflux compared with ranitidine and omeprazole, and relationship between symptoms and reflux episodes.

The objective of the open, randomised, four-period crossover study was to compare the time of onset of effect of sodium alginate (SA), omeprazole, ranitidine and control, based on oesophageal and intragastric pH and to determine any correlation between reflux symptoms and episodes in volunteers suffering from occasional gastro-oesophageal reflux. SA showed extensive prevention of acid exposure in the oesophagus compared with other treatments during the first hour. Overall, SA was more effective than control or omeprazole and comparable with ranitidine. There was little evidence of association between 'oesophageal' symptoms and reflux episodes, but associations between 'gastric' symptoms and acidity in the oesophagus, fundus and corpus were apparent. For an immediate reduction in gastro-oesophageal reflux into the oesophagus and gastric acidity during the first hour, SA was significantly superior to control, ranitidine and omeprazole. Ranitidine showed a superior effect from 2 h, consistent with its pharmacological mode of action.

Adolescent↗
PubMed2005

Crosstalk between membrane potential and cytosolic Ca2+ concentration in beta cells from Sur1-/- mice.

AIMS/HYPOTHESIS: Islets or beta cells from Sur1(-/-) mice were used to determine whether changes in plasma membrane potential (V(m)) remain coupled to changes in cytosolic Ca(2+) ([Ca(2+)](i)) in the absence of K(ATP) channels and thus provide a triggering signal for insulin secretion. The study also sought to elucidate whether [Ca(2+)](i) influences oscillations in V(m) in sur1(-/-) beta cells. METHODS: Plasma membrane potential and ion currents were measured with microelectrodes and the patch-clamp technique. [Ca(2+)](i) was monitored with the fluorescent dye fura-2. Insulin secretion from isolated islets was determined by static incubations. RESULTS: Membrane depolarisation of Sur1(-/-) islets by arginine or increased extracellular K(+), elevated [Ca(2+)](i) and augmented insulin secretion. Oligomycin completely abolished glucose-stimulated insulin release from Sur1(-/-) islets. Oscillations in V(m) were influenced by [Ca(2+)](i) as follows: (1) elevation of extracellular Ca(2+) lengthened phases of membrane hyperpolarisation; (2) simulating a burst of action potentials induced a Ca(2+)-dependent outward current that was augmented by increased Ca(2+) influx through L-type Ca(2+) channels; (3) Ca(2+) depletion of intracellular stores by cyclopiazonic acid increased the burst frequency in Sur1(-/-) islets, elevating [Ca(2+)](i) and insulin secretion; (4) store depletion activated a Ca(2+) influx that was not inhibitable by the L-type Ca(2+) channel blocker D600. CONCLUSIONS/INTERPRETATION: Although V(m) is largely uncoupled from glucose metabolism in the absence of K(ATP) channels, increased electrical activity leads to elevations of [Ca(2+)](i) that are sufficient to stimulate insulin secretion. In Sur1(-/-) beta cells, [Ca(2+)](i) exerts feedback mechanisms on V(m) by activating a hyperpolarising outward current and by depolarising V(m) via store-operated ion channels.

ATP-Binding Cassette Transporters↗
PubMed2005

Insulin secretagogues, sulfonylurea receptors and K(ATP) channels.

ATP-sensitive K+ channels, termed K(ATP) channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolarization, respectively. Examples include relaxation of vascular smooth muscle and stimulation of insulin secretion. This article reviews the cloning, molecular biology, and structure of K(ATP) channels, with particular focus on the SUR1/K(IR)6.2 neuroendocrine channels that are important for the regulation of insulin secretion. We integrate the extensive pharmacologic structure-activity-relationship data on these channels, which defines a bipartite drug binding pocket in the SUR (sulfonylurea receptor), with recent structure-function studies that identify domains of SUR and K(IR)6.2, the channel pore, which are critical for channel assembly, for gating, and for the ligand-receptor interactions that modulate channel activity. The atomic structure of a sulfonylurea in a protein pocket is used to develop insight into the recognition of these compounds. A homology model of K(ATP) channels, based on VC-MsbA, another member of the ABC protein family, is described and used to position amino acids important for the action of channel openers and blockers within the core of SUR. The model has a central chamber which could serve as a multifaceted binding pocket.

ATP-Binding Cassette Transporters↗
PubMed2005

Unequal treatment access and malaria risk in a community-based intervention program in the Philippines.

This study assesses the influence of several malaria risk factors and volunteer health worker (VHW) accessibility on parasite prevalence and treatment-seeking in a remote area of Mindanao, the Philippines. An anti-malaria program in the area seeks to devolve malaria diagnosis and treatment to the VHWs. Firstly, the relationship between malaria and demographic factors, bednet use, and access to treatment was investigated. Secondly, adults from villages with and without resident VHWs were questioned on historical and proposed treatment-seeking for fever and the capacity of the communities to support more health workers was assessed. Parasite prevalence was significantly higher among patients living in villages lacking a resident VHW (adjusted OR=3.88, p=0.02), where proposed delays in consulting VHWs and the official health service, and the use of alternative medicine, were also significantly higher. Kinship or social closeness to VHWs appears to play a role in accessibility. The educational and economic requirements demanded of VHWs impede potential expansion of the program to non-serviced villages. If the effectiveness and equity of community-based treatment strategies is to be increased, increased flexibility allowing use of local, less-educated, drug dispensers needs to be considered.

Adolescent↗
PubMed2004

Oscillations of membrane potential and cytosolic Ca(2+) concentration in SUR1(-/-) beta cells.

AIMS/HYPOTHESIS: SUR1(ABCC8)(-/-) mice lacking functional K(ATP) channels are an appropriate model to test the significance of K(ATP) channels in beta-cell function. We examined how this gene deletion interferes with stimulus-secretion coupling. We tested the influence of metabolic inhibition and galanin, whose mode of action is controversial. METHODS: Plasma membrane potential (Vm) and currents were measured with microelectrodes or the patch-clamp technique; cytosolic Ca(2+) concentrations ([Ca(2+)](c)) and mitochondrial membrane potential (DeltaPsi) were measured using fluorescent dyes. RESULTS: In contrast to the controls, SUR1(-/-) beta cells showed electrical activity even at a low glucose concentration. Continuous spike activity was measured with the patch-clamp technique, but with microelectrodes slow oscillations in Vm consisting of bursts of Ca(2+)-dependent action potentials were detected. [Ca(2+)](c) showed various patterns of oscillations or a sustained increase. Sodium azide did not hyperpolarize SUR1(-/-) beta cells. The depolarization of DeltaPsi evoked by sodium azide was significantly lower in SUR1(-/-) than SUR1(+/+) cells. Galanin transiently decreased action potential frequency and [Ca(2+)](c) in cells from both SUR1(-/-) and SUR1(+/+) mice. CONCLUSION/INTERPRETATION: The strong dependence of Vm and [Ca(2+)](c) on glucose concentration observed in SUR1(+/+) beta cells is disrupted in the knock-out cells. This demonstrates that both parameters oscillate in the absence of functional K(ATP) channels. The lack of effect of metabolic inhibition by sodium azide shows that in SUR1(-/-) beta cells changes in ATP/ADP no longer link glucose metabolism and Vm. The results with galanin suggest that this peptide affects beta cells independently of K(ATP) currents and thus could contribute to the regulation of beta-cell function in SUR1(-/-) animals.

ATP-Binding Cassette Transporters↗
PubMed2004

The effect of enrofloxacin on cell proliferation and proteoglycans in horse tendon cells.

Fluoroquinolone antibiotics have been used widely in humans and domestic animals, including horses, because of their broad-spectrum bactericidal activity, and relative safety. The use of fluoroquinolones, however, is not without risk. Tendonitis and spontaneous tendon rupture have been reported in people during or following therapy with fluoroquinolones. We have studied the effects of enrofloxacin, a fluoroquinolone antibiotic used commonly in domestic animals, on tendon cell cultures established from equine superficial digital flexor tendons. Effects on cell proliferation and morphology were studied using cell counting and scanning electron microscopy. Monosaccharide content and composition was determined by gas chromatography-mass spectrometry analysis. Western and Northern blot analyses were utilized to evaluate the synthesis and expression of two proteoglycans, biglycan and decorin. Our data demonstrate that enrofloxacin inhibits cell proliferation, induces morphological changes, decreases total monosacharide content and alters small proteoglycan synthesis at the glycosylation level in equine tendon cell cultures. These effects are more pronounced in juvenile tendon cells than in adult equine tendon cells. We hypothesize that morphological changes and inhibition of cell proliferation are a result of impaired production of biglycan and decorin, proteoglycans involved in fibrillogenesis of collagen, the most important structural component of the tendon of enrofloxacin-treated tendon cells. Our findings suggest that fluoroquinolones should be used with caution in horses, especially in foals.

Animals↗
PubMed2004

Moist wound healing: a concept that changed our practice.

Winter's seminal paper from 1962 showed that a moist wound environment accelerates healing. Since then, different types of dressings have been developed based on this concept. This paper describes their background and correct usage.

Bandages, Hydrocolloid↗
PubMed2004

Associations between dietary intake of folate and vitamins B-12 and B-6 and self-reported cognitive function and psychological well-being in Australian men and women in midlife.

OBJECTIVES: To assess dietary intake status of folate and vitamins B-12 and B-6 in 1183 middle-aged men and women, and to examine associations between dietary intake of these vitamins and self-reported cognitive function and psychological well-being. METHODS: A population-based sample of urban and rural South Australians completed questionnaires assessing demographics, background, health, and self-reported cognitive and memory functioning and psychological well-being. Usual dietary intake status was estimated using a retrospective, self-report, quantified food frequency questionnaire. RESULTS: About 20% of both men and women had intakes of folate that were below the Recommended Daily Intake for Australia. Vitamins B-12 and B-6 were positively related to memory functioning in men, and moderate dietary intake of folate and B-6 was associated with better memory functioning in women. CONCLUSIONS: Vitamin B-12 and B-6 intakes may be positively related to the memory performance of middle-aged men and intakes at around the RDI are associated with better memory functioning for women. The investigation of the dose-response effects of B vitamin supplementation on cognition and mood in middle-aged men and women using objective measures of cognition and accounting for the influence of confounding factors such age and education would be informative.

Adult↗
PubMed2003

Facilitating real-time volume interaction.

We report on efforts to provide high-level intuitive tools that exploit commodity-based computing to facilitate real-time and distributed interactions with volumetric data. These efforts include an open source volume-rendering library, a portable volume visualization application framework, and parallel volume-rendering exploiting commodity-based hardware. We present our design and implementations, as well as examples of some of the various groups currently utilizing these tools, and discuss the tradeoffs of our developments versus existing techniques.

Computer Simulation↗
PubMed2002

Temporal bone dissection simulation--an update.

We report on our continued development of a virtual simulation for temporal bone dissection that provides stereoscopic display, haptic feedback, and aural simulation into a straightforward, comprehensive learning environment. The multimodal interface provides a seamless simulation for non-deterministic drilling and cutting of bone in the surgical context, as well as an intuitive interface for the intelligent tutor for learning regional anatomy. We present novel methodologies for integrating multimodal and multiresolution data sets, including extension to functional and structural segmentation. We will present our initial efforts to validate this environment. Through continued iterations, it is our hope that the system will provide a valuable tool for training future otologic surgeons as well as an environment for the quantitative evaluation of surgical skill.

Aged↗
PubMed2001

A conserved inhibitory and differential stimulatory action of nucleotides on K(IR)6.0/SUR complexes is essential for excitation-metabolism coupling by K(ATP) channels.

The mechanism by which ubiquitous adenine nucleotide-gated K(IR)6.0(4)/SUR(4) channels link membrane excitability with cellular metabolism is controversial. Is a decreased sensitivity to inhibitory ATP required, or is the Mg-ADP/ATP-dependent stimulatory action of the ATPase, sulfonylurea receptor (SUR), on K(IR) sufficient to elicit a physiologically significant open channel probability? To evaluate the roles of nucleotide inhibition versus stimulation, we compared K(IR)6.1-based K(NDP) channels with K(IR)6.2-based K(ATP) channels and all possible K(IR)6.1/6.2 hybrids. Although K(NDP) channels are thought to be poorly sensitive to inhibitory ATP and to require Mg-nucleotide diphosphates for activity, we demonstrate that, like K(ATP), and hybrid channels, they are inhibited with an IC(50(ATP)) 100-fold lower than [ATP](i). K(IR)6.1 is, however, more efficiently stimulated by SUR than K(IR)6.2, thus providing a mechanism for differential nucleotide regulation, in addition to the known differential interactions of Mg-nucleotides with SUR isoforms. The on-cell and spontaneous activities of K(NDP), K(ATP), and hybrid channels identified in native cells, are different; thus, their similar IC(50(ATP)) values argue the regulatory "beta" SUR subunits play a preeminent role in coupling excitation to metabolism and pose questions about the physiologic significance of models, which assume the ATP insensitivity of open K(IR)s.

Adenosine Triphosphate↗
PubMed2001

The effect of weight-loss dieting on cognitive performance and psychological well-being in overweight women.

This study investigated the effect of a weight reduction diet on cognitive performance and psychological well-being among overweight women. A total of 42 women undertook a 12-week weight reduction diet while 21 women maintained their usual diet and exercise habits for 12 weeks. All women completed neuropsychologcial tests of speed of information processing, executive function, working memory, immediate and delayed recall and recognition, and verbal ability. They also completed measures of weight locus of control, dieting beliefs, self-esteem, mood and dysfunctional attitudes, before and after the 12-week interval. Being on the diet had a minimal impact on cognitive performance and a positive effect on emotional eating, feelings of depression and dysfunctional attitudes. A sense of control over weight and eating behaviour increased among the dieters, but an internal locus of control was negatively related to self-esteem.

Adult↗
PubMed2001

Adult age differences in self-ordered pointing task performance: contributions from working memory, executive function and speed of information processing.

This study investigated adult age differences in, and predictors of, the performance of a test of executive function, the Self-Ordered Pointing Task (SOPT; Petrides & Milner, 1982). Performance on the SOPT is thought to rely on high level working memory processes, therefore, measures reflecting the common operationalization of working memory, along with measures of executive function and speed of information processing, were investigated as predictors of SOPT performance. Younger (aged 17-48 years) and older (aged 65-88 years) adults completed a 16-item, 3-trial, modified version of Shimamura and Jurica's (1994) version of the SOPT, and tests assessing working memory, executive function and speed. Results showed that younger adults made fewer errors on the SOPT. There was no age difference in the frequency of use of a clustering strategy. Contrary to expectations, working memory was not a good predictor of individual or age differences in SOPT performance. Instead, speed of processing, and to a lesser extent, measures of perseverations, made larger unique and overlapping contributions to the variance. The SOPT and its association, or dissociation, with other measures of working memory may be useful for research into the nature of working memory and executive function and the theoretical links between them.

Adolescent↗
PubMed2001

Gene expression analysis with the parametric bootstrap.

Recent developments in microarray technology make it possible to capture the gene expression profiles for thousands of genes at once. With this data researchers are tackling problems ranging from the identification of 'cancer genes' to the formidable task of adding functional annotations to our rapidly growing gene databases. Specific research questions suggest patterns of gene expression that are interesting and informative: for instance, genes with large variance or groups of genes that are highly correlated. Cluster analysis and related techniques are proving to be very useful. However, such exploratory methods alone do not provide the opportunity to engage in statistical inference. Given the high dimensionality (thousands of genes) and small sample sizes (often <30) encountered in these datasets, an honest assessment of sampling variability is crucial and can prevent the over-interpretation of spurious results. We describe a statistical framework that encompasses many of the analytical goals in gene expression analysis; our framework is completely compatible with many of the current approaches and, in fact, can increase their utility. We propose the use of a deterministic rule, applied to the parameters of the gene expression distribution, to select a target subset of genes that are of biological interest. In addition to subset membership, the target subset can include information about relationships between genes, such as clustering. This target subset presents an interesting parameter that we can estimate by applying the rule to the sample statistics of microarray data. The parametric bootstrap, based on a multivariate normal model, is used to estimate the distribution of these estimated subsets and relevant summary measures of this sampling distribution are proposed. We focus on rules that operate on the mean and covariance. Using Bernstein's Inequality, we obtain consistency of the subset estimates, under the assumption that the sample size converges faster to infinity than the logarithm of the number of genes. We also provide a conservative sample size formula guaranteeing that the sample mean and sample covariance matrix are uniformly within a distance epsilon > 0 of the population mean and covariance. The practical performance of the method using a cluster-based subset rule is illustrated with a simulation study. The method is illustrated with an analysis of a publicly available leukemia data set.

Journal Article↗
PubMed2001

B vitamins, cognition, and aging: a review.

Recent research has highlighted the potential impact of nutritional factors and individual micronutrients on the brain and on cognitive performance, especially in older adults. The B vitamins, folate, B12, and B6, are of particular interest because even subclinical deficiencies in these vitamins are thought to be relatively common in the general population and in older adults in particular. Recent cross-sectional and longitudinal studies have provided evidence for an association between these B vitamins and many aspects of cognitive performance and have raised the possibility that even subclinical differences in nutritional status may have a subtle influence on aspects of cognitive performance, especially in older adults and in clinical populations. Preliminary evidence also indicates the effectiveness of supplementation in enhancing cognitive performance in older adults. Important considerations for future research include the use of placebo-controlled intervention studies, sensitive outcome measures of cognitive performance, and exploration of bioavailability and dose-response relationships.

Aged↗