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Biomedical subjects

S Barnes

Publications and source records attributed to S Barnes.

At least 37 records · Page 2Linked to original sources

Oestrogens and their promiscuous receptors: confronting reality.

The binding sites of the oestrogen receptors alpha and beta have a structural requirement for ligands with two oxygen atoms (one of which is phenolic) spaced 11-12 A apart. They are open to many non-steroidal compounds, such as those from plants and the chemical industry. The importance of this interaction is the subject of current food safety research. This article examines the methods of assessment of oestrogenicity and their relationship to physiological events.

Biological Transport↗

The state of ambulatory surgery and perianesthesia nursing.

The continued success of the ambulatory surgery environment of care has been achieved through patient, physician, and nursing staff satisfaction. The growth in this industry has been greatly influenced by advances in technology, as well as the development and administration of newer anesthetic agents. The implications delineated in this article provide an overview of what is in store for the specialty of perianesthesia nursing. Issues of competency, professional excellence, patient expectations, continuous quality improvement, research, and ethics have become part of the daily lexicon. Never before has the professional nurse been counted on for so much, and future expectations of the nurse continue to grow. To survive, the nurse needs to expand the boundaries of nursing practice as they have been defined. Nurses are the backbone of the delivery of patient care, nurses are on the front line guiding the patient through every care decision, and nurses are positioned to influence the continued evolution of ambulatory surgery and perianesthesia nursing care.

Ambulatory Surgical Procedures↗

The epidemiology of prostate cancer in the United States.

OBJECTIVES: To provide a review of prostate cancer epidemiology. DATA SOURCES: Journal articles and the Surveillance, Epidemiology, and End Results database. CONCLUSIONS: Numerous risk factors for prostate cancer have been identified. Incidence and mortality rates are higher in certain countries and among racial ethnic groups. Environmental and dietary influences are likely to be significant causes of prostate cancer. Distinguishing those cancers that are clinically significant from those that are not remains a central concern in prostate cancer research. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of epidemiologic patterns and trends will assist nurses in recognising persons at high risk for the development of prostate cancer and should result in tailored educational interventions.

Black or African American↗

Adverse impact of cigarette smoking on dimensions of health-related quality of life in persons with HIV infection.

Because effects of cigarette smoking on health-related quality of life (HRQL) have not been well described, we carried out a cross-sectional assessment of HRQL using the Medical Outcomes Survey Scale adapted for patients with human immunodeficiency virus (MOS-HIV questionnaire) in 585 HIV-infected homosexual/bisexual men, injection drug users, and female partners enrolled in a multicenter, prospective study of the pulmonary complications of HIV infection. Mean scores for the following dimensions of HRQL were calculated: general health perception, quality of life, physical functioning, bodily pain, social functioning, role functioning, energy, cognitive functioning, and depression. A multivariate model was used to determine the impact on HRQL of the following factors: smoking, CD4 loss, acquired immune deficiency syndrome (AIDS) diagnoses, number of symptoms, study site, education, injection drug use, gender, and age. Current smoking was independently associated with lower scores for general health perception, physical functioning, bodily pain, energy, role functioning, and cognitive functioning (all with p < 0.05). We conclude that patients with HIV infection who smoke have poorer HRQL than nonsmokers. These results support the use of smoking cessation strategies for HIV-infected persons who smoke cigarettes.

Adult↗

The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen.

PURPOSE: We performed a randomized double-blind crossover pilot study in elderly men with elevated prostate specific antigen (PSA) on the effects of the daily consumption of 2 soy beverages, each containing 20 gm. of isolated soy protein, on the isoflavone concentration in blood and urine, and on the 3 serum biomarkers cholesterol, PSA and the soluble p105 component of the p185erbB-2 proto-oncogene. MATERIALS AND METHODS: A total of 34 men supplemented their diet by consuming 1 of 2 soy protein beverages assigned randomly twice daily for a 6-week period. In a second 6-week period they consumed the other soy protein beverage. The beverage ISP+ provided 42 mg. of genistein and 27 mg. of daidzein daily, whereas the other beverage, ISP-, provided only 2.1 and 1.3 mg. of these isoflavones daily, respectively. Blood and 24-hour urine samples were obtained before the study, at 2-week intervals during the study and 2 weeks after study completion. RESULTS: ISP+ and to a lesser extent ISP- substantially increased the serum concentration and urinary output of the isoflavones and their metabolites. Serum cholesterol was significantly decreased by ISP+ irrespective of the order in which the 2 soy beverages were administered and in apparent correlation with the total isoflavone concentration. There was no significant effect of the soy beverages on serum PSA and p105erbB-2 values. CONCLUSIONS: This study reveals that short-term exposure of elderly men with elevated serum PSA values to soy protein containing isoflavones decreases serum cholesterol but not the serum biomarkers PSA and p105erbB-2.

Aged↗

The future of prostate cancer prevention.

The dramatic international variation in prostate cancer mortality rates suggest an environmental influence. This combined with a building understanding of the genetic mechanisms of carcinogenesis encourages a search for ways to prevent it. Androgenic stimulation over a period of time has been suggested a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. Decreasing androgenic stimulation of the prostate with 5-alpha-reductase inhibitors such as finasteride has been shown to decrease prostate size and may prevent prostate cancer. A large, long-term clinical trial is underway using finasteride to determine if it can prevent prostate cancer. Results are expected in 2004. Epidemiologic and laboratory studies also suggest that high selenium and vitamin E intake lowers risk of prostate cancer. Recent serendipitous findings of two randomized clinical trials support the hypothesis that selenium and vitamin administration will decrease prostate cancer risk. A study to assess these compounds is beginning. Other promising, but less developed, interventions in chemoprevention of prostate cancer include vitamin D supplementation and diet modification. All will need to be rigorously evaluated before they can be advocated for prostate cancer prevention.

5-alpha Reductase Inhibitors↗

Enhanced antioxidant activity after chlorination of quercetin by hypochlorous acid.

BACKGROUND: Several epidemiological studies indicate that moderate consumption of red wine decreases both the incidence and mortality associated with cardiovascular disease. Quercetin and rutin (quercetin-3-rutinoside) are polyphenols present in relatively large concentrations in red wine and may play a role in this cardioprotective phenomenon. The precise mechanisms of cardioprotection remain unclear but may involve the action of these polyphenols as antioxidants, which attenuate the tissue injury that results from the production of proinflammatory oxidants such as hypochlorous acid (HOCl). METHODS: To study the interaction of these polyphenols with proinflammatory oxidants, we mixed quercetin or rutin with HOCl (0-150 microM) and analyzed the reaction products by high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. RESULTS: Stable mono- and dichlorinated derivates were detected for both quercetin and the glycoside derivative, rutin, which suggests that both the conjugated and unconjugated forms of quercetin reacted with HOCl similarly. Chlorination of quercetin occurred only at two sites, and the derivates (6-chloroquercetin, 6,8-dichloroquercetin) were more potent antioxidants toward oxidative modification of low-density lipoproteins and ABTS radical formation than the unmodified form. CONCLUSIONS: These data suggest that under certain pathological conditions in vivo (e.g., inflammation), flavonols may be converted to chlorinated derivates, which exhibit an enhanced antioxidant potential and thereby play a role in cardioprotection.

Analysis of Variance↗

Biochemical structural analysis of the lantibiotic mutacin II.

Mutacin II is a post-translationally modified lantibiotic peptide secreted by Streptococcus mutans T8, which inhibits the energy metabolism of sensitive cells. The deduced amino acid sequence of promutacin II is NRWWQGVVPTVSYECRMNSWQHVFTCC, which is capable of forming three thioether bridges. It was not obvious, however, how the three thioether bridges are organized. To examine the bridging, the cyanogen bromide cleavage products of mutacin II and its variants generated by protein engineering, C15A, C26A, and C15A/C26A, were analyzed by mass spectrometry. Analysis of the wild type molecule and the C15A variant excluded several possibilities and also indicated a high fidelity of formation of the thioether bridges. This allowed us to further resolve the structure by analysis (mass spectrometry and tandem mass spectrometry) of the cyanogen bromide cleavage fragments of the C26A and C15A/C26A mutants. Nuclear magnetic resonance analysis established the presence of one and two dehydrobutyrine residues in mutacin II and the C15A variant, respectively, thus yielding the final structure. The results of this investigation showed that the C-terminal part contains three thioether bridges connecting Cys residues 15, 26, and 27 to Ser/Thr residues 10, 12 and 19, respectively, with Thr(25) being modified to dehydrobutyrine.

Amino Acid Sequence↗

Nitric oxide reaction with lipid peroxyl radicals spares alpha-tocopherol during lipid peroxidation. Greater oxidant protection from the pair nitric oxide/alpha-tocopherol than alpha-tocopherol/ascorbate.

The reactions of nitric oxide ((.)NO) and alpha-tocopherol (alpha-TH) during membrane lipid oxidation were examined and compared with the pair alpha-TH/ascorbate. Nitric oxide serves as a more potent inhibitor of lipid peroxidation propagation reactions than alpha-TH and protects alpha-TH from oxidation. Mass spectrometry, oxygen and (.)NO consumption, conjugated diene analyses, and alpha-TH fluorescence determinations all demonstrated that (.)NO preferentially reacts with lipid radical species, with alpha-TH consumption not occurring until (.)NO concentrations fell below a critical level. In addition, alpha-TH and (.)NO cooperatively inhibit lipid peroxidation, exhibiting greater antioxidant capacity than the pair alpha-TH/ascorbate. Pulse radiolysis analysis showed no direct reaction between (.)NO and alpha-tocopheroxyl radical (alpha-T(.)), inferring that peroxyl radical termination reactions are the principal lipid-protective mechanism mediated by (.)NO. These observations support the concept that (.)NO is a potent chain breaking antioxidant toward peroxidizing lipids, due to facile radical-radical termination reactions with lipid radical species, thus preventing alpha-TH loss. The reduction of alpha-T(.) by ascorbate was a comparatively less efficient mechanism for preserving alpha-TH than (.)NO-mediated termination of peroxyl radicals, due to slower reaction kinetics and limited transfer of reducing equivalents from the aqueous phase. Thus, the high lipid/water partition coefficient of (.)NO, its capacity to diffuse and concentrate in lipophilic milieu, and a potent reactivity toward lipid radical species reveal how (.)NO can play a critical role in regulating membrane and lipoprotein lipid oxidation reactions.

Amidines↗

The enzymatic formation of novel bile acid primary amides.

Bifunctional peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the copper-, ascorbate-, and O(2)-dependent cleavage of C-terminal glycine-extended peptides and N-acylglycines to the corresponding amides and glyoxylate. The alpha-amidated peptides and the long-chain acylamides are hormones in humans and other mammals. Bile acid glycine conjugates are also substrates for PAM leading to the formation of bile acid amides. The (V(MAX)/K(m))(app) values for the bile acid glycine conjugates are comparable to other known PAM substrates. The highest (V(MAX)/K(m))(app) value, 3.1 +/- 0.12 x 10(5) M(-1) s(-1) for 3-sulfolithocholylglycine, is 6.7-fold higher than that for d-Tyr-Val-Gly, a representative peptide substrate. The time course for O(2) consumption and glyoxylate production indicates that bile acid glycine conjugate amidation is a two-step reaction. The bile acid glycine conjugate is first converted to an N-bile acyl-alpha-hydroxyglycine intermediate which is ultimately dealkylated to the bile acid amide and glyoxylate. The enzymatically produced bile acid amides and the carbinolamide intermediates were characterized by mass spectrometry and two-dimensional (1)H-(13)C heteronuclear multiple quantum coherence NMR.

Bile Acids and Salts↗

Isoflavonoids and chronic disease: mechanisms of action.

Soy and its isoflavones are associated with a reduced risk of chronic disease. The mechanisms of action of isoflavones include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as cellular antioxidants. Although estrogen receptor beta binds genistein with an affinity close to that of 17beta-estradiol, it remains to be determined whether it is a mediator of genistein's activity in vivo. Genistein's inhibition of protein tyrosine kinases is not limited to direct effect on these kinases, but may result from alteration in kinase expression. Genistein is not a particularly good scavanger of cellular oxidants; however, it reacts vigorously with the prooxidant hypochlorous acid, produced by neutrophils as part of the inflammatory response. The chlorinated isoflavones may have altered biochemical and biological effects compared to their parent compounds and may provide increased protection against inflammatory disease.

Animals↗

Suppressive actions of betaxolol on ionic currents in retinal ganglion cells may explain its neuroprotective effects.

Betaxolol, a beta 1-selective adrenoceptor antagonist, is widely used in the treatment of glaucoma. In addition to its ocular hypotensive effects, betaxolol has been suggested to act as a retinal neuroprotective agent (Osborne et al., 1997). To investigate possible mechanisms underlying the neuroprotective effects, we tested the actions of betaxolol on ion channels and calcium signaling in isolated retinal ganglion cells. Betaxolol (50 microM) reduced by about 20% the high-voltage-activated (HVA) Ca channel currents in ganglion cells isolated from tiger salamander retina. In contrast, the beta 1-adrenoceptor antagonists propranolol (10 microM) and timolol (50 microM) had no inhibitory actions on HVA Ca channel currents. The L-type Ca channel antagonist, nisoldipine, blocked the HVA Ca channel current partially and the remaining current was not inhibited by betaxolol. Outward current was inhibited in the presence of betaxolol. Both iberiotoxin (IBTX; 10 nM), a selective inhibitor of large-conductance Ca-activated K channels, and Cd2+ (100 microM), which suppresses Ca-activated K channels subsequent to its block of Ca channels, reduced outward current and the remaining current was not blocked significantly with betaxolol. In the presence of betaxolol, Na channel currents were reduced by about 20%, as were currents evoked by glutamate (10 mM) and GABA (1 mM). Current clamp recordings from isolated ganglion cells showed that betaxolol had several effects on excitability: spike height decreased, repetitive spike activity was suppressed, spike width increased and hyperpolarization following spikes was reduced. Calcium imaging in isolated rat retinal ganglion cells revealed that betaxolol inhibited glutamate-induced increases in [Ca2+]i. These results suggest that betaxolol has a diversity of suppressive actions on ganglion cell ion channels and that, as a consequence, one of the net actions of the drug is to reduce Ca2+ influx. The subsequent reduction in [Ca2+]i may contribute to the apparent neuroprotective actions of betaxolol in promoting ganglion cell survival following ischemic insult, as may occur in glaucoma and retinal disease.

Action Potentials↗

Heterogeneity of O-glycosylation in the hinge region of human IgA1.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was applied to studies of the molecular heterogeneity of desialylated human IgA1 hinge region glycopeptides released with two IgA1 proteases. Typically, the hinge region of an alpha1 chain contains three to five O-linked glycan chains. Variants of the hinge region peptides released from IgA1(Kni) myeloma protein carrying 0, 1, 2, or 3 GalNAc residues were observed in the mass spectra as well as the nonglycosylated peptide. Variable numbers of Gal residues indicated additional heterogeneity in O-glycosylation of IgA1. In the hinge region preparation from normal human serum IgA1, glycopeptides carrying 2, 3, 4, or 5 GalNAc residues with variable numbers of Gal residues were detected. In conclusion, our new approach using the site-specific cleavage with two IgA1 proteases allowed precise and sensitive MALDI-TOF mass spectrometric analysis of O-glycosylation heterogeneity in IgA1 hinge region.

Amino Acid Sequence↗

Retention and changes of soy isoflavones and carotenoids in immature soybean seeds (Edamame) during processing.

Isoflavones and carotenoids in four experimental genotypes and Hutcheson cultivar soybeans were evaluated as a function of processing treatments and maturity. Total isoflavone and carotenoid contents were affected by genotypes and maturity stages (p < 0.0001). Total isoflavones ranged from 472 microg/g (in NTCPR93-40) to 2280 microg/g (in Hutcheson). Lutein contents ranged from 895 (in NTCPR93-286) to 2119 (in Honey Brown), and beta-carotene ranged from 291 (in Hutcheson) to 491 (in NICPR92-40) microg/100 g. Mean total isoflavone retention percentages in immature Hutcheson soybeans were 46% (boiling), 53% (freezing), and 40% (freeze-drying). Mean retentions of lutein and beta-carotene, respectively, were 92 and 73% in frozen, 62 and 62% in boiled, and 34 and 27% in freeze-dried soybeans. Boiling caused a substantial increase in daidzin, genistin, and genistein. The results show that post-harvest changes in total isoflavones and carotenoids in soybeans are influenced by processing methods, but genotype has an effect on isoflavone and carotenoid profiles during seed development.

Carotenoids↗