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Biomedical subjects

S Jones

Publications and source records attributed to S Jones.

At least 91 records · Page 5Linked to original sources
PubMed2002

Tobacco point of sale advertising increases positive brand user imagery.

OBJECTIVES: To determine the potential impact of point of sale advertising on adolescents so as to inform changes to the Tobacco Control Act. DESIGN: Participants were randomly assigned to one of two conditions. In the control condition, students were exposed to a photograph of a packet of cigarettes; in the intervention condition, students were exposed to an ad for cigarettes, typical of point of sale advertising posters. All students then rated the brand user on a set of 12 bipolar adjectives. Two brands were used in the study: Benson & Hedges, and Marlboro. SUBJECTS: One hundred year (grade) 6 and 7 students (age range 10-12 years), from four Western Australian metropolitan primary schools, participated in the study. RESULTS: In a majority of the brand user descriptions, the cigarette advertisements increased brand user imagery in a positive way, especially for Benson & Hedges. For example, participants viewing the Benson & Hedges advertisement, as distinct from those viewing the Benson & Hedges pack only, were more likely to describe the Benson & Hedges user as relaxed, interesting, cool, rich, adventurous, and classy. Relative to the Marlboro pack only, the Marlboro ad increased positive perceptions of the Marlboro user on adventurous, interesting, and relaxed. CONCLUSIONS: The results presented here support restrictions being placed on advertising at point of sale, since such ads have the potential to increase positive brand user imagery directly in the situation where a product purchase can take place, and hence the potential to increase the likelihood of impulse purchasing.

Adolescent↗
PubMed2002

Resuspension of DNA sequencing reaction products in agarose increases sequence quality on an automated sequencer.

We are investigating approaches to increase DNA sequencing quality. Since a majorfactor in sequence generation is the cost of reagents and sample preparations, we have developed and optimized methods to sequence directly plasmid DNA isolated from alkaline lysis preparations. These methods remove the costly PCR and post-sequencing purification steps but can result in low sequence quality when using standard resuspension protocols on some sequencing platforms. This work outlines a simple, robust, and inexpensive resuspension protocol for DNA sequencing to correct this shortcoming. Resuspending the sequenced products in agarose before electrophoresis results in a substantial and reproducible increase in sequence quality and read length over resuspension in deionized water and has allowed us to use the aforementioned sample preparation methods to cut considerably the overall sequencing costs without sacrificing sequence quality. We demonstrate that resuspension of unpurified sequence products generated from template DNA isolated by a modified alkaline lysis technique in low concentrations of agarose yields a 384% improvement in sequence quality compared to resuspension in deionized water. Utilizing this protocol, we have produced more than 74,000 high-quality, long-read-length sequences from plasmid DNA template on the MegaBACET 1000 platform.

Cell Fractionation↗
PubMed2002

Dysbetalipoproteinaemia--clinical and pathophysiological features.

OBJECTIVES: Dysbetalipoproteinaemia (type III hyperlipidaemia, broad-beta disease) is a highly atherogenic genetic disorder of lipoprotein metabolism. It presents with a severe mixed hyperlipidaemia in which the ratio of total cholesterol to triglycerides is typically 2:1. There is a high incidence of atherosclerotic complications and severe hypertriglyceridaemia may cause pancreatitis. Highly effective therapy is available and affected families also benefit from genetic counselling. We present a review of our experience with dysbetalipoproteinaemia at the lipid clinic of Groote Schuur Hospital to enhance awareness of this serious condition, for which the index of suspicion should be raised. DESIGN: Retrospective review of case records, 1969-2001. SETTING: Lipid clinic of Groote Schuur Hospital, Cape Town. SUBJECTS: Patients with dysbetalipoproteinaemia diagnosed by the presence of cholesterol-enriched very-low-density lipoproteins (VLDL) and/or dyslipidaemia associated with homozygosity for apolipoprotein E2 or carriers of the apoE2 (Arg145-->Cys) mutation. RESULTS: One hundred and five patients were identified, 55 of whom were male and 50 female. The age at presentation was 48.8 +/- 11.1 years (mean, standard deviation). Total cholesterol was 12.0 +/- 5.5 mmol/l and plasma triglycerides 8.3 +/- 9.8 mmol/l. The ratio (by mass) of cholesterol to triglycerides within VLDL was 0.52 +/- 0.17, while VLDL cholesterol to plasma triglycerides was 0.33 +/- 0.09. Fifty patients were epsilon 2 homozygotes while 22 carried the apoE2 (Arg145-->Cys) mutation. Palmar crease xanthomas occurred in 20% of patients, cutaneous xanthomas in 18%, and tendon xanthomas in 13%. Coronary artery disease was found in 47% of patients and peripheral vascular disease in 20%. Fibrates were the most commonly used hypolipidaemic agents (48%), while 31% of patients received combination therapy with a fibrate and statin. Statin monotherapy was used in 11% of patients and a few patients were treated with niacin or required no drug therapy. The treated cholesterol was 5.7 +/- 2.4 mmol/l, with plasma triglycerides of 2.7 +/- 1.9 mmol/l. CONCLUSIONS: Dysbetalipoproteinaemia is a highly atherogenic disorder and is extremely responsive to therapy. A significant proportion of dysbetalipoproteinaemia locally is caused by the apoE2 (Arg145-->Cys) mutation and is therefore dominantly inherited. This mutation is particularly prevalent in the black community where dysbetalipoproteinaemia may be undiagnosed in many patients. Patients with severe mixed hyperlipidaemia or clinical stigmata of dyslipidaemia should be assessed at a lipid clinic for a specific diagnosis and initiation of therapy.

Adolescent↗
PubMed2002

Predictors of cognitive change from preclinical to clinical Alzheimer's disease.

We examined individual-difference variables in relation to the rate of change in global cognitive performance, measured by the MMSE, from 3 years prior to diagnosis of Alzheimer's disease (AD) to the time of diagnosis. The population-based sample consisted of 230 incident AD persons who were followed over a 3-year interval. The average annual decline in MMSE was 1.81 points. Being older and acquiring additional diseases during the 3 years preceding diagnosis predicted a faster rate of decline in global cognitive functioning. However, other individual difference variables such as sex, education, depression, vitamin levels (vitamin B12 and folic acid), apolipoprotein status, and social network did not precipitate the rate of decline in the preclinical phase of AD.

Aged↗
PubMed2001

Crystallohydrodynamics for solving the hydration problem for multi-domain proteins: open physiological conformations for human IgG.

Hydrodynamic methods provide a route for studying the low-resolution conformation--in terms of time-averaged spatial orientation of the Fab' and Fc domains relative to each other--of the human IgG subclasses, IgG1, IgG2, IgG3 and IgG4 in the environment in which many exist naturally---a solution. Representative modelling strategies are now available using 'shell-bead' or 'shell' modelling of the surface of the molecules with the size-independent programme SOLPRO [J. Garcia de la Torre, S.E. Harding, B. Carrasco, Eur. Biophys. J. 28 (1999) 119-132]. The shell model fits to the equivalent inertial surface ellipsoids of the published crystal structures for the Fab' and Fc domains of IgG are made and an apparent hydration delta(app) of 0.51g/g for Fab' and 0.70 g/g for the glycoprotein Fc are obtained, which yield an average value of (0.59+/-0.07) g/g for the intact antibody (2 Fab'+1 Fc). The relative orientations of these domains for each of the IgG subclasses is then found (using where appropriate a cylindrical hinge) from SOLPRO by modelling the Perrin function, P (i.e. 'frictional ratio due to shape') using this delta(app) and experimentally measured sedimentation coefficients. All the IgG subclasses appear as open, rather than compact structures with the degree of openness IgG3>IgG1>(IgG2, IgG4), with IgG3 and IgG1 non-coplanar. The hingeless mutant IgGMcg, with s degrees (20,w) approximately 6.8 S yields a coplanar structure rather similar to IgG2 and IgG4 and consistent with its crystallographic structure. The extension of this procedure for representing solution conformations of other antibody classes and other multi-domain proteins is indicated.

Crystallography, X-Ray↗
PubMed2001

Partial leptin deficiency and human adiposity.

The adipocyte-derived hormone leptin is crucial for energy homeostasis in mammals; mice and humans without it suffer from a voracious appetite and extreme obesity. The effect on energy balance of variations in plasma leptin above a minimal threshold is uncertain, however, particularly in humans. Here we examine a group of individuals who are genetically partially deficient in leptin, and show that differences in circulating leptin levels within the range found in normal human populations can directly influence the laying down of fat tissue (adiposity).

Adipose Tissue↗
PubMed2001

Neurotrophin-4 deficient mice have a loss of vagal intraganglionic mechanoreceptors from the small intestine and a disruption of short-term satiety.

Intraganglionic laminar endings (IGLEs) and intramuscular arrays (IMAs) are the two putative mechanoreceptors that the vagus nerve supplies to gastrointestinal smooth muscle. To examine whether neurotrophin-4 (NT-4)-deficient mice, which have only 45% of the normal number of nodose ganglion neurons, exhibit selective losses of these endings and potentially provide a model for assessing their functional roles, we inventoried IGLEs and IMAs in the gut wall. Vagal afferents were labeled by nodose ganglion injections of wheat germ agglutinin-horseradish peroxidase, and a standardized sampling protocol was used to map the terminals in the stomach, duodenum, and ileum. NT-4 mutants had a substantial organ-specific reduction of IGLEs; whereas the morphologies and densities of both IGLEs and IMAs in the stomach were similar to wild-type patterns, IGLEs were largely absent in the small intestine (90 and 81% losses in duodenum and ileum, respectively). Meal pattern analyses revealed that NT-4 mutants had increased meal durations with solid food and increased meal sizes with liquid food. However, daily total food intake and body weight remained normal because of compensatory changes in other meal parameters. These findings indicate that NT-4 knock-out mice have a selective vagal afferent loss and suggest that intestinal IGLEs (1) may participate in short-term satiety, probably by conveying feedback about intestinal distension or transit to the brain, (2) are not essential for long-term control of feeding and body weight, and (3) play different roles in regulation of solid and liquid diet intake.

Afferent Pathways↗
PubMed2001

Binding of transcriptional activators to sigma 54 in the presence of the transition state analog ADP-aluminum fluoride: insights into activator mechanochemical action.

Conformational changes in sigma 54 (sigma(54)) and sigma(54)-holoenzyme depend on nucleotide hydrolysis by an activator. We now show that sigma(54) and its holoenzyme bind to the central ATP-hydrolyzing domains of the transcriptional activators PspF and NifA in the presence of ADP-aluminum fluoride, an analog of ATP in the transition state for hydrolysis. Direct binding of sigma(54) Region I to activator in the presence of ADP-aluminum fluoride was shown and inferred from in vivo suppression genetics. Energy transduction appears to occur through activator contacts to sigma(54) Region I. ADP-aluminum fluoride-dependent interactions and consideration of other AAA+ proteins provide insight into activator mechanochemical action.

Adenosine Diphosphate↗
PubMed2001

The effect of hormone replacement therapy on cardiovascular risk factors in type 2 diabetes: a randomized controlled trial.

BACKGROUND: Postmenopausal women with diabetes are at high risk for cardiovascular disease, compared with their nondiabetic counterparts. Combined continuous hormone replacement therapy (HRT) is associated with improvements in serum lipoprotein levels in nondiabetic women; however, the effect in women with diabetes has not been determined. We evaluated the effect of combined continuous HRT on lipoprotein and coagulation factor concentrations and glycemic control in postmenopausal women with type 2 diabetes mellitus. METHODS: In a randomized controlled crossover study, 61 subjects received combined continuous HRT or placebo. Each treatment phase was of 6 months' duration, with an 8-week washout phase between treatment phases. RESULTS: Total cholesterol concentration decreased by 7% (95% confidence interval [CI], 4%-11%) during HRT. For low-density lipoprotein concentration, the mean decrease with HRT was 12% (95% CI, 6%-17%). Apolipoprotein B levels decreased in keeping with the reduction in low-density lipoprotein cholesterol concentrations. There were no significant changes in concentrations of high-density lipoprotein, its subfractions, or triglycerides. Lipoprotein(a) and fibrinogen concentrations were reduced by 21% (95% CI, 10%-31%) and 8% (95% CI, 2%-13%), respectively, with HRT. Fructosamine concentrations declined by 5% (95% CI, 2%-9%) during HRT. CONCLUSIONS: In postmenopausal women with type 2 diabetes mellitus, combined continuous HRT has beneficial effects on lipoprotein concentrations and improves some markers of coagulation and glycemic control.

Aged↗
PubMed2001

Gastrointestinal projection maps of the vagus nerve are specified permanently in the perinatal period.

The vagal innervation of the proximal gastrointestinal (GI) tract is lateralized. To determine whether this pattern is specified as early as the perinatal period, neonatal rat pups were given unilateral cervical vagotomies. Separate groups received (1) transections below the left nodose ganglion, (2) left cervical resections that included removal of the nodose ganglion, or (3) sham surgeries. At 4 months of age, each animal's vagal afferent projections from the unoperated side were mapped by injecting the nodose with WGA-HRP, preparing the stomach as wholemounts, and processing the tissue with tetramethyl benzidine. The two types of vagal afferent endings in GI smooth muscle, namely intraganglionic laminar endings and intramuscular arrays, were surveyed separately, and their regional distributions were mapped. Changes in the nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMNX) were assessed with cell counts and area measurements. Neonatal loss of the vagus innervating one side of the GI tract, with or without ganglionectomy, did not cause the unoperated vagus to sprout to the denervated side. In addition, removal of the projections to the one side of the target organ did not produce a reorganization of the projection maps of the unoperated vagus within its normal or ipsilateral wall of the GI tract. Although the regional patterns of the unoperated ipsilateral vagus were not affected, the packing densities of both types of afferents supplied by this trunk were moderately reduced. The DMNX of the vagotomized side displayed extensive (approximately 83%) neuronal loss; the DMNX on the unoperated side as well as the NST on both sides exhibited limited (approximately 20--25%) losses. The lack of a peripheral projection field reorganization -- except for a moderate down-regulation -- after complete unilateral denervation suggests that both the laterality and the afferent terminal phenotypes (or target tissues) of the vagus in the proximal GI tract are specified by postnatal day one in the rat. The present results, taken together with other observations, also suggest that three different combinations of signals orchestrate the commitments of vagal afferents respectively to (1) the side of the organ, (2) the region within the organ wall, and (3) the accessory and innervated tissues that complex with the fully differentiated ending.

Animals↗
PubMed2001

Fulminant leptospirosis in a patient with human immunodeficiency virus infection: case report and review of the literature.

We report a case of fulminant leptospirosis that was acquired in New York City by a patient with underlying infection with human immunodeficiency virus (HIV). Review of the literature on leptospirosis in HIV-infected persons showed that all patients were severely ill but responded well to treatment, which highlights the importance of recognizing this potentially life-threatening illness, especially in unusual settings.

AIDS-Related Opportunistic Infections↗
PubMed2001

The 5' flanking region of the human bone morphogenetic protein-7 gene.

We describe here the cloning and characterization of the 5' flanking region of the human Bone Morphogenetic Protein-7 (BMP-7) gene from a 3.3 kb genomic DNA fragment. Functional analysis by transient transfection using the luciferase reporter gene indicated that this region had a low basal promoter activity in human Wilm's tumor derived renal (G401) and rat osteoblast (ROS 17/2.8) cell lines. Sequential deletion analysis of the promoter revealed sequences whose presence correlated with decreased expression of the reporter gene. Coexpression of transcription factors involved in epithelial/mesenchymal interactions during kidney and eye development dramatically stimulated the expression of the reporter gene from the putative BMP-7 promoter. Finally, a subset of agents that upregulated the expression of the reporter gene from the cloned promoter were also shown to increase the expression of the endogenous BMP-7 in G401 and ROS cell lines in vitro.

Amino Acid Sequence↗
PubMed2001

Erratum.

Explore the source record for details and available documents.

Journal Article↗
PubMed2001

The cohesin complex: sequence homologies, interaction networks and shared motifs.

BACKGROUND: Cohesin is a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis. The links are formed during DNA replication and destroyed during the metaphase-to-anaphase transition. In budding yeast, the 14S cohesin complex comprises at least two classes of SMC (structural maintenance of chromosomes) proteins - Smc1 and Smc3 - and two SCC (sister-chromatid cohesion) proteins - Scc1 and Scc3. The exact function of these proteins is unknown. RESULTS: Searches of protein sequence databases have revealed new homologs of cohesin proteins. In mouse, Mmip1 (Mad member interacting protein 1) and Smc3 share 99% sequence identity and are products of the same gene. A phylogenetic tree of SMC homologs reveals five families: Smc1, Smc2, Smc3, Smc4 and an ancestral family that includes the sequences from the Archaea and Eubacteria. This ancestral family also includes sequences from eukaryotes. A cohesion interaction network, comprising 17 proteins, has been constructed using two proteomic databases. Genes encoding six proteins in the cohesion network share a common upstream region that includes the MluI cell-cycle box (MCB) element. Pairs of the proteins in this network share common sequence motifs that could represent common structural features such as binding sites. Scc2 shares a motif with Chk1 (kinase checkpoint protein), that comprises part of the serine/threonine protein kinase motif, including the active-site residue. CONCLUSIONS: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex. We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs. The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

Amino Acid Motifs↗
PubMed2001

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗