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S English

Publications and source records attributed to S English.

11 recordsLinked to original sources

Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging.

PURPOSE: To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. MATERIAL AND METHODS: Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. RESULTS: Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. CONCLUSION: Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors.

Animals↗

Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope.

The importance of cardiac output (CO) to blood pressure level during vasovagal syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients, CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min, respectively. In TS patients, CO decreased during the first minute (from 3.3 +/- 0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001) than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in CO may contribute to hypotension some minutes before syncope occurs.

Adult↗

Reversible glutathionylation regulates actin polymerization in A431 cells.

In response to growth factor stimulation, many mammalian cells transiently generate reactive oxygen species (ROS) that lead to the elevation of tyrosine-phosphorylated and glutathionylated proteins. While investigating EGF-induced glutathionylation in A431 cells, paradoxically we found deglutathionylation of a major 42-kDa protein identified as actin. Mass spectrometric analysis revealed that the glutathionylation site is Cys-374. Deglutathionylation of the G-actin leads to about a 6-fold increase in the rate of polymerization. In vivo studies revealed a 12% increase in F-actin content 15 min after EGF treatment, and F-actin was found in the cell periphery suggesting that in response to growth factor, actin polymerization in vivo is regulated by a reversible glutathionylation mechanism. Deglutathionylation is most likely catalyzed by glutaredoxin (thioltranferase), because Cd(II), an inhibitor of glutaredoxin, inhibits intracellular actin deglutathionylation at 2 microM comparable with its IC(50) in vitro. Moreover, mass spectral analysis showed efficient transfer of GSH from immobilized S-glutathionylated actin to glutaredoxin. Overall, this study revealed a novel physiological relevance of actin polymerization regulated by reversible glutathionylation of the penultimate cysteine mediated by growth factor stimulation.

Actins↗

Representations of knowledge about dominoes in demented and normal elderly players.

1. Dementia patients who retain musical and game-playing skills exhibit impaired performance on explicit memory tests of knowledge about their retained skill. 2. Dementia patients who retain skill at playing dominoes can answer complex questions about the play of the game almost as well as normal elderly domino players when the questions are presented with real dominoes. 3. The aim of this study was to determine if skilled dementia patients could answer questions about domino play when the stimuli were two-dimensional drawings of dominoes. 4. Seventeen dementia patients and eight normal elderly domino players were tested on two forms of the Domino Quiz: first with real dominoes, then with two-dimensional drawings; other neuropsychological tests were given at the same time. 5. Fourteen of the 17 patients and all of the controls showed no decline in answering questions about domino play when two-dimensional drawings were used. These patients showed retained symbolic processing of information about dominoes despite declines in overall mental status, generation of words from specific semantic categories, and recognition memory for domino terminology. 6. Because the 14 patients with retained domino skill performed as accurately as controls on both administrations of a letter cancellation task, the ability to process familiar symbols may be important to their game-playing skill.

Aged↗

Long-lived picture priming in normal elderly persons and demented patients.

Normal elderly control participants showed short-term (10-min delay) and long-term (12 months delay) priming on the Gollin Figures Test. Nearly all patients with Alzheimer's disease or vascular dementia showed short-term priming, but the magnitude of their priming was less than that of controls. Significant long-term priming was not observed for the dementia groups. Differences between controls and dementia patients on the short-term priming test may depend upon structural-perceptual processes that are intact in dementia patients and controls and explicit memory functions available only to controls. The same model could account for differences between normal elderly and dementia patients on the long-term priming test, but several other explanations are also plausible.

Aged↗

Expression of game-related and generic knowledge by dementia patients who retain skill at playing dominoes.

Patients with dementia who remain skilled at musical performance or playing bridge fail explicit memory tests for information related to their skills, suggesting that implicit memory mediates their preserved skills. To reexamine this issue, 23 dementia patients and 15 elderly controls of comparable domino-playing skill were compared on tests of naming, verbal fluency, and domino knowledge. On an explicit test of domino knowledge, the patients scored well below the elderly controls, performing no better than students who were unfamiliar with the game. But when game-like situations were created with real dominoes, both the skilled controls and the patients with dementia chose optimal moves and verbally explained their choices equally well. On naming and fluency tests, the skilled patients showed no advantage over patients of comparable dementia severity who had no retained skill. In dementia, some complex knowledge seems intact but is accessible only in particular contexts.

Aged↗

Stimulation of bicarbonate secretion by alpha- and beta-adrenoceptor agonists in rat caecum in vitro.

This study examines the effects of adrenergic drugs on bicarbonate secretion by the rat caecum in vitro. Noradrenaline, phenylephrine but not clonidine, stimulated secretion in a concentration-related manner. Noradrenaline responses were antagonised by alprenolol (20 microM) but not phentolamine (10 microM) whilst phenylephrine was antagonised by phentolamine (10 microM), prazosin (5 microM) but not yohimbine (5 microM), alprenolol or tetrodotoxin (1 microM). Replacement of mucosal Cl- abolished the phenylephrine response. Combined stimulation with maximum concentrations of phenylephrine and isoprenaline gave a response which was not greater than that to either agonist alone but it did involve both alpha- and beta-adrenoceptors as judged from the effects of alprenolol and phentolamine either alone or combined. Submaximum concentrations of the two agonists did show additive responses. The results show that alpha 1- but not alpha 2-adrenoceptor agonists stimulate bicarbonate secretion and may act on the same transport mechanism as beta-adrenoceptor agonists. Noradrenaline stimulates via beta-adrenoceptors.

Adrenergic alpha-Agonists↗