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Biomedical subjects

L Hughes

Publications and source records attributed to L Hughes.

At least 73 records · Page 4Linked to original sources
PubMed1990

Vitamin E activity of 1-thio-alpha-tocopherol as measured by the rat curative myopathy bioassay.

The bioactivity of the acetate of the all-racemic, 1-thio analog of alpha-tocopherol (all-rac-1-thio-alpha-tocopheryl acetate) has been determined by measuring its ability to decrease plasma levels of pyruvate kinase in vitamin E deficient rats using the curative myopathy bioassay. The thio analog is only 0.22 times as active as RRR-alpha-tocopheryl acetate and is therefore approximately 0.33 times as active as all-rac-alpha-tocopheryl acetate, since the latter has been shown to be 1.47 times less active than RRR-alpha-tocopheryl acetate in the same bioassay (H. Weiser, M. Vecchi and M. Schlachter, Internat. J. Vit. Nutr. Res., 55, 149-158 (1985)). The 0.33:1.0 ratio is similar to the ratio of 0.41:1.0 measured for the in vitro antioxidant activities of the corresponding free phenols. This finding lends further support to our view that the vitamin E activity in the curative myopathy bioassay of close structural analogs of alpha-tocopherol is determined primarily by the in vitro antioxidant activity of the analog relative to alpha-tocopherol, consistent with the belief that vitamin E functions primarily as a general purpose, lipid-soluble antioxidant in mammals.

Animals↗
PubMed1990

Staying well. Factors contributing to successful community adaptation.

1. Friends were rated as the most important factor in assisting former psychiatric patients to avoid rehospitalization. 2. When respondents were asked to comment on rehospitalization in their own words, the most frequent responses dealt with factors related to keeping active, developing a healthy lifestyle and positive self-image, and accepting their illness. 3. Self-help groups, community health workers, and community nurses were rated as the least beneficial in preventing rehospitalization.

Adaptation, Psychological↗
PubMed1990

Examination of vascular anastomoses during liver transplantation by intraoperative Doppler duplex scanning.

Intraoperative examination of the arterial and portal vein anastomoses was performed in 16 liver transplant patients using duplex scanning. Two major defects and three minor defects were found in 5 arterial anastomoses. Major defects were defined as those associated with an audibly abnormal Doppler signal, a defect greater than 3 mm in length or greater than 50% luminal narrowing. Minor defects were defects visible by ultrasound but not meeting the above criteria. The major defects were repaired and scans following repair were without evidence of defects. The three minor defects were ignored. A nearly occluding thrombus was found in the portal vein of one patient. A thrombectomy was performed successfully. All patients have done well postoperatively. This report suggests that intraoperative duplex scanning may be of value in detecting technical imperfections in the vascular anastomoses during liver transplantation. Detection of a major defect intraoperatively allows immediate repair.

Adult↗
PubMed1990

Nascent VLDL from liver perfusions of cynomolgus monkeys are preferentially enriched in RRR- compared with SRR-alpha-tocopherol: studies using deuterated tocopherols.

The transport and secretion of vitamin E in lipoproteins have been studied in cynomolgus monkeys fed tocopherols labeled with different amounts of deuterium. The animals were fed a single dose of vitamin E containing 60 mumol of each 2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate; alpha-tocopherol with natural stereochemistry), 2S,4'R,8'R-alpha-5-(C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate; alpha-tocopherol with unnatural stereochemistry), and 2R,4'R,8'R-gamma-(3,4-2H)tocopherol (d2-RRR-gamma-tocopherol; gamma-tocopherol with natural stereochemistry). Chylomicrons, as well as the other plasma lipoproteins, contained equal concentrations of all three tocopherols at the earliest time points after feeding suggesting that all three tocopherols were absorbed equally. At later times plasma lipoproteins became preferentially enriched in d6-RRR-alpha-tocopherol. This is likely to be due to hepatic secretion of VLDL (very low density lipoproteins) and other lipoproteins, which were enriched in d6-RRR-alpha-tocopherol, as demonstrated in the lipoproteins isolated from perfused livers that had been obtained 24 h following the administration of the deuterated tocopherols. Taken together these data demonstrate that the liver, not the intestine, is the likely site of discrimination between tocopherol isomers and that the liver secretes nascent lipoproteins preferentially enriched in d6-RRR-alpha-tocopherol.

Animals↗
PubMed1989

The relationship of age, level of formal education, and duration of employment toward attitudes concerning the use of computers in the workplace.

The introduction of computer technology in the Canadian health care environment necessitates an adaptation by hospital employees in order to perform their jobs. One thousand twenty-two hospital staff were surveyed immediately following their initial orientation to computers. The survey identified attitudes toward change, and the use of computers in the workplace. Demographic data and job classifications of all respondents were tabulated. Hypotheses were tested regarding the relationships between age, formal education, and duration of employment, and attitudes toward computers and change. Results indicated a generally positive response toward the use of computers in the workplace and to change in general. However, statistically significant results were obtained indicating that age, level of education, and length of employment affect the degree of positive response to both computers and change. The results suggest that demographic variables such as age, level of education, and employment duration must be taken into consideration when planning for the implementation of computer systems in the health care setting.

Adult↗
PubMed1988

Inhibition of the chemotactic peptide-induced elevation of intracellular calcium in differentiated human leukemic (HL-60) cells by the phorbol ester phorbol 12-myristate 13-acetate.

The chemotactic peptide formylmethionylleucylphenylalanine rapidly elevated the intracellular calcium concentration, in a concentration-dependent manner, of human leukemic (HL-60) cells which had been differentiated to polymorphonuclear leukocyte-like cells by pretreatment with dimethyl sulfoxide (1.3%). Preincubation of the cells with phorbol 12-myristate 13-acetate, a protein kinase C-activating phorbol ester, inhibited the formylmethionylleucylphenylalanine-induced rise in intracellular calcium in a time- and concentration-dependent manner. 4 alpha-Phorbol 12,13-didecanoate, which does not activate protein kinase C, was inactive in this capacity. The use of calcium-free medium suggested that the elevation of intracellular calcium by formylmethionylleucylphenylalanine consisted of rapid intracellular release followed by calcium influx. Phorbol 12-myristate 13-acetate (10(-7) M) inhibited both components of the elevation of intracellular calcium, whereas 10(-8) M phorbol 12-myristate 13-acetate inhibited only the calcium influx. The influx of calcium was not prevented by verapamil, which blocks the voltage-dependent calcium channels. These data suggest that, in differentiated HL-60 cells, 12-O-tetradecanoylphorbol-13-acetate rapidly inhibits both the intracellular release of calcium and calcium influx through non-voltage-dependent calcium channels in response to formylmethionylleucylphenylalanine.

Calcium↗
PubMed1988

Structure and dynamics of alpha-tocopherol in model membranes and in solution: a broad-line and high-resolution NMR study.

Nuclear magnetic resonance has been applied to study the conformational dynamics of alpha-tocopherol (vitamin E) in solution and in model membranes. In nonviscous solution, 1H nuclear magnetic resonance (NMR) showed that alpha-tocopherol is in rapid equilibrium between two or more puckered conformers of its heterocyclic ring. The most likely conformers to be so involved are the two half-chair forms. Deuterium NMR spectra of specifically deuteriated alpha-tocopherol in multilamellar dispersions of egg phosphatidylcholine, measured in the liquid-crystalline state, were characteristic of axially symmetric motional averaging. The orientation of the rotational axis within the molecular framework was determined. Studies on oriented multilamellar membranes revealed that this axis is perpendicular to the surface of the membrane. The profile of quadrupolar splittings along the hydrophobic tail does not have a plateau, in contrast to that of the fatty acyl chains of the membrane lipids. Longitudinal relaxation times (T1) were short. The presence of a minimum in their temperature dependence shows that molecular motion with an effective correlation time tau eff approximately equal to 3 X 10(-9)s is responsible for relaxation. However, the temperatures and absolute values of the minima depend on the position of the deuterium in the molecule, demonstrating that tau eff represents a complex blend of motions.

Deuterium↗
PubMed1988

Comparison of free alpha-tocopherol and alpha-tocopheryl acetate as sources of vitamin E in rats and humans.

The uptake of alpha-tocopherol from 2R,4'R,8'R-alpha-tocopherol and 2R, 4'R, 8'R-alpha-tocopheryl acetate has been compared in rats and humans. The two forms of vitamin E were compared simultaneously in each subject (rat and human) by using a combination of deuterium-substitution and gas chromatography-mass spectrometry (GC-MS) to distinguish and measure the competitive uptake of alpha-tocopherol from an orally ingested mixture of the acetate and the free phenol forms. When rats were dosed in a manner analogous to that used in traditional bioassays, i.e., providing the two forms of vitamin E once daily in tocopherol-stripped corn oil for four successive days immediately prior to sacrifice, the net uptake of alpha-tocopherol from the free phenol form was only half that from the acetate. This result is consistent with the greater activity of the acetate that had been observed previously in bioassays. However, when the two forms of tocopherol were intubated into rats as a single dose mixed in with an aqueous bolus of standard laboratory diet, the amount of alpha-tocopherol taken up from the free form after 24 hr was very similar to that derived from the acetate. In five adult humans, competitive uptake studies of the two forms after a single dose taken with a meal showed that the amount of alpha-tocopherol from the free phenol form was equal to that from the acetate in plasma and red blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Expression of class I and II major histocompatibility complex antigens in Wilms' tumour and normal developing human kidney.

The Wilms' tumour is a solid childhood tumour of the kidney, consisting of blastema, tubules and mesenchyme. Embryonic tumours, such as Wilms', may arise as a result of a developmental disturbance in differentiation. The expression of class I and II major histocompatibility complex (MHC) antigens was investigated on 6 Wilms' tumours and related to that in the developing human kidney in this immunohistological study, using a panel of monoclonal antibodies. The Wilms' tumour blastemal cells were class I MHC antigen negative, but differentiated structures were positive. Class II MHC antigens were not observed in Wilms' tumours. In the developing human kidney class I MHC antigen expression was observed on glomeruli from 8 weeks and on tubules from 13 weeks gestational age. Class II MHC antigen expression was observed on glomeruli from 11 weeks and on tubules from 13 weeks gestation. These results suggest that the blastemal cells within the Wilms' tumour may reflect an early stage of development with respect to the expression of MHC antigens.

Adult↗
PubMed1987

Biokinetics of and discrimination between dietary RRR- and SRR-alpha-tocopherols in the male rat.

The net rates of uptake of the natural (2R,4'R,8'R) diastereoisomer of alpha-tocopherol (alpha-T) and the biodiscrimination relative to its 2S-epimer (2S,4'R,8'R) have been measured, in two experiments, for the blood and 21 tissues of male Sprague-Dawley rats fed over a period of several months diets containing deuterium-substituted forms of the alpha-T acetates. Gas chromatography-mass spectrometry was used to measure the amount of deuterated tocopherols taken up relative to the amount of nondeuterated tocopherol remaining. The measurements were performed at different times after the rats, placed for one month on a basal diet containing nondeuterated, natural alpha-T acetate, were switched to a diet containing the same total quantity of deuterated forms of either natural alpha-T acetate or a mixture of the acetates of the 2R- and 2S-epimers (i.e., ambo-alpha-T acetate). In experiment 1 the source of vitamin E in the replacement diet was trideuterio-2R,4'R,8'R-alpha-T acetate. The data obtained provide the first direct measure of the rate at which natural vitamin E is replaced and augmented in the tissues of growing animals under normal laboratory dietary conditions. There are dramatic differences in the tissue kinetics; for example, the apparent half-life of vitamin E, i.e., the time at which the total amount of ingested trideuterio-alpha-T taken up is the same as the amount of nondeuterated alpha-T remaining, varies from ca. 1 wk for the lung to ca. 11 wk for the spinal cord. In experiment 2 the vitamin E in the replacement diet was an equimolar mixture of trideuterio-2S,4'R,8'R- and hexadeuterio-2R,4'R,8'R-alpha-T acetates. The results show that there is a preferential uptake of the natural diastereoisomer of alpha-T by all tissues (except the liver during the first month). Examination of fecal material reveals that the biodiscrimination begins in the gut; the incomplete hydrolysis of the acetates shows clearly that this reaction proceeds to a greater extent with the natural diastereoisomer. The greatest discrimination of all the tissues examined was found to occur in the brain. After five months, the level of the deuterated natural diastereoisomer was more than five times that of the deuterated 2S-epimer. These results have potential implications for human nutrition.

Animals↗
PubMed1987

The emergence of work-centred issues in consultative work: an observation.

During two separate series of consultative meetings for professionals engaged in direct work with adolescents, the authors noticed that the issues brought to consultation showed a definite and sustained shift away from matters to do with the workers' clientele, and towards matters concerning their working relationships and work settings. The possible causes and effects of this shift in the focus of work is discussed.

Adolescent↗
PubMed1987

Intraoperative assessment of renal and visceral artery reconstruction: the role of duplex scanning and spectral analysis.

To refine our ability to assess intraoperatively renal and visceral reconstructions, we have investigated the usefulness of combined duplex scanning and Doppler spectral analysis to determine the technical adequacy and flow characteristics of these repairs. We studied 62 patients (116 arteries) who underwent renal (83 arteries) or visceral (13) reconstruction by transaortic endarterectomy (76), autogenous graft (12) or prosthetic (5) bypass, reimplantation (2), and dilation (1). Twenty-six nonreconstructed vessels were also studied, including preoperative arteries (6), unrepaired arteries (14), and normal renal arteries (donor nephrectomies) (6). Duplex scanning was performed by means of a 7.5 or 10 MHz probe placed in a sterile glove and plastic sleeve. Peak (Vs) and mean (Vm) velocities measured in meters per second were subsequently calculated from frequency spectral analysis. Spectral broadening (SB) and aortic inflow data were also collected and analyzed. There were no complications related to ultrasound scanning. Mean scan time was 7.8 minutes. Fourteen of 26 nonreconstructed vessels (54%) appeared normal by duplex scanning, including all six control (normal) renal arteries. Sixty-five reconstructed arteries (68%) appeared normal, 27 had various minor defects, and four had major defects (three occlusions and one floating thrombus). The major defects were repaired, whereas minor ones were not. Confirmatory studies were obtained in 19 (73%) nonoperated and 73 (76%) operated vessels. There were two false negative duplex studies (sensitivity 89%) and 17 false positive duplex studies--all minor defects (specificity 77%). The predictive value of duplex scans in detecting the presence of confirmed defects was Tau = 0.47 (p = 0.01). Although SB correlated with B-mode imaging alone (Tau = 0.21, p = 0.07), it added no independent value in predicting the results of a confirmatory study. No other variable (Vs, Vm, or aortic inflow) added to the duplex scan in predicting an abnormal confirmatory study. Detailed renal and visceral artery spectral analysis data are provided for validation of this technique and comparison with transcutaneous studies. These data suggest that the requirement for reliable and immediate assessment of renal and visceral reconstructions, particularly those involving transaortic extraction endarterectomy, is satisfied by duplex scanning.

Endarterectomy↗
PubMed1986

A new vitamin E analogue more active than alpha-tocopherol in the rat curative myopathy bioassay.

Vitamin E owes its biological effects to its antioxidant activity. Kinetic and mechanistic studies on phenolic antioxidants in vitro have led us to design and synthesize all-rac-2,4,6,7-tetramethyl-2-(4',8',12'-trimethyltridecyl) -5-hydroxy-3,4-dihydrobenzofuran, 3. In the rat curative myopathy bioassay the acetate of this compound has 1.5-1.9 times the bioactivity of all-rac-alpha-tocopherol acetate. This represents the first time that a rationally designed synthetic 'vitamin' has been found to have more activity in vivo than the corresponding natural vitamin.

Animals↗