Search PubMed⌕ Search

Biomedical subjects

C Saunders

Publications and source records attributed to C Saunders.

At least 37 records · Page 2Linked to original sources

[Use of food composition tables in evaluation of risk of vitamin A deficiency].

One hundred and ninety-eight 24 h-recall questionnaires from pregnant attendees of the public health services in Rio de Janeiro, Brazil, were analyzed, using 5 different Food Composition Tables. The differences in calculated intakes were as high as 88% (793 to 1494 micrograms RE). The differences were significant at the 5% level using Fishers test. The INCAP table was considered more adequate because it gives more attention to the different conversion factors for carotenoids. However, the INCAP Table does not include several foods frequently consumed in Brazil, neither does it show values for culinary preparations and industrialized foods. This study shows that there is a need to improve the tools to evaluate vitamin A intake if we wish to assess nutritional risk in populations.

Analysis of Variance↗

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Cardiovascular Diseases↗

Localization and trafficking of alpha2-adrenergic receptor subtypes in cells and tissues.

The three alpha2-adrenergic receptor (alpha2AR) subtypes, all of which couple to multiple effectors via Gi/Go proteins, perform various functions, including the mediation of decreases in adenylyl cyclase activity, activation of receptor-mediated K+ channels, and inhibition of voltage-gated Ca2+ channels. The alpha2ARs are polarized in many target cells, such as neurons in the peripheral and central nervous system and in intestinal and renal epithelia. Precise targeting and polarization of molecules are crucial for many physiological processes, and may confer a degree of specificity that, in the case of the adrenergic receptors, could represent a reasonable strategy by which catecholamines coordinate cellular function in a highly specific way. Receptors also redistribute in response to agonist occupancy by means of sequestration, endocytosis, recycling, or, alternatively, down-regulation (degradation). The focus of this review is to compare the similarities and differences among the three alpha2AR subtypes in terms of specificity, signaling, and trafficking. It is anticipated that a molecular understanding of receptor trafficking will lead to novel therapeutic strategies for diseases linked to aberrant adrenergic receptor function or localization.

Adrenergic Agonists↗

The role of oocyte transcription, the 5'UTR, and translation repression and derepression in Drosophila gurken mRNA and protein localization.

The establishment of the major body axes of the Drosophila egg and future embryo requires strict regulation of gurken mRNA and protein localization. Here, we show that grk mRNA and protein localization is dependent on synthesis of grk transcripts in the oocyte nucleus and on RNA localization elements in the 5' portion of the transcript. We also show that gurken mRNA and protein localization is dependent on region-specific translation of gurken transcripts and identify K10 as a probable negative regulator of gurken translation.

3' Untranslated Regions↗

Langer's axillary arch in association with sentinel lymph node.

Langer's axillary arch is a relatively rare anatomical variation of latissimus dorsi muscle insertion. The clinical importance of this condition in axillary lymph node dissection (ALND) and lymphoedema as well as latissimus dorsi flap reconstruction has been described previously. Axillary vein obstruction in association with this condition has also been reported. We report two cases of Langer's axillary arch encountered during sentinel lymph node (SLN) biopsy which had some bearing on the procedure.

Journal Article↗

Setting up a breast cancer family history clinic.

Breast cancer causes around 21,000 deaths per year in the UK, the vast majority of these occurring in women aged over 50 years with no genetic predisposition to the disease. Screening and symptomatic services for these women, although by no means perfect or homogeneous, have gradually improved over the last 10 years and, perhaps as a result of this, together with increased use of adjuvant systemic therapy, mortality in this group has fallen. Despite this reassuring state of affairs, media interest in the disease and patients' perception of their risk of developing breast cancer have risen. Part of this is undoubtedly due to the new scientific developments in cancer genetics and, in particular, identification of the BRCA1 gene in 1994 and BRCA2 gene shortly afterwards. These genes are dominantly inherited with up to 80% penetrance; thus, women (and occasionally men) inherit these genes and have a high lifetime risk of developing breast cancer, usually at a younger age than average and possibly of a more aggressive phenotype. Unaffected family members can now be screened and, if they prove carriers, screening for early detection and prevention strategies such as bilateral prophylactic mastectomy can be offered. Because of the high risk of ovarian cancer in BRCA1 carriers, screening or prophylactic ovariectomy may also be considered.

Adult↗

Targeting of G protein-coupled receptors to the basolateral surface of polarized renal epithelial cells involves multiple, non-contiguous structural signals.

Truncations and chimeras of the alpha2A-adrenergic receptor (alpha2AAR) were evaluated to identify membrane domains responsible for its direct basolateral targeting in Madin-Darby canine kidney cells. An alpha2AAR truncation, encoding transmembrane (TM) regions 1-5, was first delivered basolaterally, but within minutes appeared apically, and at steady-state was primarily lateral in its immunocytochemical localization. A TM 1-5 truncation with the third intracellular loop revealed more intense lateral localization than for the TM 1-5 structure, consistent with the role of the third intracellular loop in alpha2AAR stabilization. Addition of TM 6-7 of A1 adenosine receptor (A1AdoR) to alpha2AARTM1-5 creates a chimera, alpha2AARTM1-5/A1AdoRTM6-7, which was first delivered apically, resulting either from loss of alpha2AAR sorting information in TM 6-7 or acquisition of apical trafficking signals within A1AdoRTM6-7. Evidence that alpha2AARTM6-7 imparts basolateral targeting information is revealed by the significant basolateral localization of the A1AdoRTM1-5/alpha2AARTM6-7 and A1AdoRTM1-5/alpha2AARTM6-7+i3 chimeras, in contrast to the dominant apical localization of A1AdoR. These results reveal that sequences within TM 1-5 and within TM 6-7 of the alpha2AAR confer basolateral targeting, providing the first evidence that alpha2AAR basolateral localization is not conferred by a single region but by non-contiguous membrane-embedded or proximal sequences.

Animals↗

Caring for cancer.

Explore the source record for details and available documents.

History, 20th Century↗

Disruption of microtubules reveals two independent apical targeting mechanisms for G-protein-coupled receptors in polarized renal epithelial cells.

G-protein-coupled receptors demonstrate differing trafficking itineraries in polarized Madin-Darby canine kidney (MDCK II) cells. The alpha2A adrenergic receptor (alpha2AAR) is directly delivered to the basolateral subdomain; the A1 adenosine receptor (A1AdoR) is apically enriched in its targeting; and the alpha2BAR subtype is randomly delivered to both domains but selectively retained basolaterally (Keefer, J. R., and Limbird, L. E. (1993) J. Biol. Chem. 268, 11340-11347; Saunders, C., Keefer, J. R., Kennedy, A. P., Wells, J. N., and Limbird, L. E. (1996) J. Biol. Chem. 271, 995-1002; Wozniak, M., and Limbird, L. E. (1996) J. Biol. Chem. 271, 5017-5024). The present studies explore the role of the polarized cytoskeleton in localization of G-protein-coupled receptors in MDCK II cells. Nocodazole or colchicine, which disrupt microtubules, did not perturb lateral localization of alpha2AR subtypes but led to a relocalization the A1AdoR to the basolateral surface, revealed by immunocytochemical and metabolic labeling strategies. Conversely, the apical component of the random delivery of alpha2BAR was not affected by these agents, suggesting microtubule-dependent and -independent apical targeting mechanisms for G-protein-coupled receptors in polarized cells. Apparent rerouting of the apically targeted A1AdoR was selective for microtubule-disrupting agents, since cytochalasin D, which disrupts actin polymerization, did not alter A1AdoR or alpha2BAR localization or targeting. These data suggest that multiple apical targeting mechanisms exist for G-protein-coupled receptors and that microtubule-disrupting agents serve as tools to probe their different trafficking mechanisms.

Animals↗

Peroxynitrite causes energy depletion and increases permeability via activation of poly (ADP-ribose) synthetase in pulmonary epithelial cells.

Recent studies show that peroxynitrite is a potent trigger of DNA strand breakage, which in turn activates the nuclear repair enzyme poly (ADP-ribose) synthetase (PARS), resulting in a cellular energy deficit. Here we present evidence that treatment of A549 human pulmonary epithelial cells with peroxynitrite (1 mM) results in ADP-ribosylation, NAD+ depletion, inhibition of mitochondrial respiration, and increased epithelial paracellular permeability. The PARS inhibitor 3-aminobenzamide (1 mM) provided a significant, partial protection against the energetic and functional changes. Similarly, inhibition of PARS activity by 3-aminobenzamide reduced the peroxynitrite-induced suppression of mitochondrial respiration in BEAS-2B human bronchial epithelial cells. Thus, PARS activation and energy depletion represents one of the pathways of peroxynitrite-mediated epithelial toxicity. Inhibition of PARS may improve cellular energy homeostasis in pathophysiologic conditions associated with peroxynitrite generation.

Benzamides↗

The application of meta-analysis in assessing racial differences in the effects of antihypertensive medication.

Meta-analysis is an important technique for synthesizing research findings. Although the statistical foundations of meta-analysis continue to be debated, few question its value as a rigorous framework for organizing literature reviews. In recent years, there has been increasing emphasis on the use of meta-analysis not only to summarize the central tendency of findings but also to explain variation between studies. This article reviews the major steps in a meta-analysis with an emphasis on comparative analysis of subgroups of studies. A meta-analysis of the antihypertensive efficacy of calcium channel blockers is used to illustrate how a comparative analysis can be applied to investigate racial variation in the effects of calcium channel blockers. A statistically significant trend is found between the proportion of African-American hypertensive subjects and the mean reduction in blood pressure. Meta-analytic techniques also are applied to explore possible confounders due to differences in research design and patient characteristics.

Age Factors↗

Evidence for a single non-arachidonic acid-specific fatty acyl-CoA synthetase in heart which is regulated by Mg2+.

Previous reports indicated that arachidonic acid is incorporated into the isolated perfused rabbit heart in preference to other fatty acids, and that incorporation of arachidonic acid, but not other fatty acids, is inhibited during Mg2+ depletion. In this study, we have not been able to demonstrate an arachidonic acid-specific fatty acyl-CoA synthetase in rat or rabbit heart by hydroxyapatite chromatography. Kinetic evidence was consistent with a single enzyme, as the slopes of pseudo-Hill plots were not significantly different from -1. The single fatty acyl-CoA synthetase present appears to prefer C18:0 unsaturated fatty acids to arachidonate, and had about the same affinity for C10:0 -C14:0 saturated fatty acids as for arachidonate. At 35 microM arachidonate, enzyme velocity increased as the total Mg2+ was increased from 3 to 80 mM. Calculated [MgATP] indicated that the MgATP complex was not rate-limiting. At low concentrations, Mn2+ and Ni2+ supported activity, but Cu2+ and Zn2+ did not. Low Ca2+ concentrations activated only oleic acid conversion. Kinetic analysis indicated that the Vmax of the enzyme was increased with increasing concentrations of ionized Mg2+ for both oleic acid and arachidonic acid. The data are constant with the hypothesis that Mg2+ has a direct effect on fatty acyl-CoA synthetase activity, and suggest that preference for oleic acid and arachidonic acid can be influenced by the ionic milieu.

Adenosine Triphosphate↗