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Biomedical subjects

A J Stewart

Publications and source records attributed to A J Stewart.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antioxidant flavonols from fruits, vegetables and beverages: measurements and bioavailability.

Flavonols are polyphenolic secondary plant metabolites that are present in varying levels in commonly consumed fruits, vegetables and beverages. Flavonols have long held an interest for nutritionists, which has increased following a Dutch study in the early 1990's showing that dietary intake of flavonols was inversely correlated with the incidence of coronary heart disease. The main factors that have hindered workers in the field of flavonol research are (i) the accurate measurement of these compounds in foods and biological samples, and (ii) a dearth of information on their absorption and metabolism. This review aims to highlight the work of the authors in attempting to clarify the situation. The sensitive and selective HPLC procedure to identify and quantify common flavonols and their sugar conjugates is described. In addition, the results of an on-going screening program into the flavonol content of common produce and beverages are presented. The bioavailability of dietary flavonols is discussed with reference to an intervention study with onions, as well as pilot studies with tea, red wine and cherry tomatoes. It is concluded that flavonols are absorbable and accumulate in plasma and that consuming high flavonol-containing varieties of fruits and vegetables and particular types of beverages could increase their circulatory levels.

Antioxidants↗
PubMed1999

"If I had it to do over again...": midlife review, midcourse corrections, and women's well-being in midlife.

Regrets about early adult life choices, expressed in midlife, are examined as a source of motivation for life changes in later midlife in 2 samples of women. Replicated findings with longitudinal data indicate that regret motivates goal setting but is not associated with actually making desired life changes. In both samples, women who had regrets about early adult life choices but did not make relevant life changes were lower in later well-being than both women with regrets who did make such changes and women without regrets. Compared with women who transformed regrets into life changes, women who did not were lower in effective instrumentality and higher in rumination, though they did not appear to face more barriers to change. Analyses with longitudinal data indicated that both rumination and effective instrumentality mediated the relationship between regret and well-being for women who did not translate regret into life changes.

Adaptation, Psychological↗
PubMed1999

Pseudo-Gaucher cells in myelodysplasia.

A case of myelodysplastic syndrome is reported, in which the bone marrow contained many cells with the typical light microscopic morphology of Gaucher cells. In the absence of any evidence of inherited Gaucher's disease, these cells are considered to be pseudo-Gaucher cells, which have been described previously in association with other haematological diseases. This is the first report of their occurrence in myelodysplastic syndrome.

Aged↗
PubMed1999

Warfarin-induced skin necrosis.

Skin necrosis is a rare but serious side-effect of treatment with warfarin. At particular risk are those with various thrombophilic abnormalities, especially when warfarinization is undertaken rapidly with large loading doses of warfarin. With the increasing number of patients anticoagulated as out-patients for thromboprophylaxis, we are concerned that the incidence of skin necrosis may increase. If skin necrosis does occur, prompt remedial action may be of benefit in preventing permanent tissue damage.

Adult↗
PubMed1998

Women's personality in middle age. Gender, history, and midcourse corrections.

This article examines several key features of the course of adult development in the cohort of women born during the baby boom. By focusing on the women in this group and comparing their experience with that of older cohorts and research on men, the authors demonstrate the need for models of aging that take account of the inter-sections of history, gender, and individual development. Concepts proposed as universal features of middle age (midlife crisis, generativity, aging), as well as those proposed as specific to women (empty nest, menopause) are examined. Perhaps most important, certain features not commonly viewed as particularly important in women's middle aging (midlife review, identity, confident power) are shown to be central. The need for further research examining these same processes among men and different groups of women is underscored.

Adult↗
PubMed1998

Psychological predictors of good health in three longitudinal samples of educated midlife women.

Concurrent and longitudinal associations between cognitive and affective personality variables--intellectual efficiency (IE), anxiety, and hostility--and observer ratings of physical health were examined in 3 longitudinal samples of women: Mills Longitudinal Study (n = 101); Radcliffe Study (RS, n = 118); and University of California, San Francisco Study (n = 44). Observer ratings of health were based on participants' reports of health problems. The California Psychological Inventory (H. G. Gough, 1996) IE, Hostility, and Anxiety Scales were used in all studies at Times 1 and 2, except in RS, when at Time 1 the Zung Anxiety (W. K. Zung, 1971) and the Profile of Mood States (D. M. McNair, M. Lorr, & L. F. Droppleman, 1971) Hostility Scales were used. In the majority of analyses, IE was positively associated with good health, and Anxiety and Hostility were negatively associated with health. IE was the strongest independent predictor of health, indicating that cognitive characteristics may have an important role in health and should be examined further.

Adult↗
PubMed1998

Traits and motives: toward an integration of two traditions in personality research.

After reviewing classic and current conceptions of trait (as measured by questionnaires) and motive (as measured by the Thematic Apperception Test [TAT] or other imaginative verbal behavior), the authors suggest that these 2 concepts reflect 2 fundamentally different elements of personality--conceptually distinct and empirically unrelated. The authors propose that traits and motives interact in the prediction of behavior: Traits channel the behavioral expression of motives throughout the life course. The authors illustrate this interactive hypothesis in 2 longitudinal studies, focusing on the broad trait of extraversion and the 2 social motives of affiliation and power. In interaction with extraversion, both motives show predicted and replicated relations to independently measured life outcomes in the domains of relationships and careers. Extraversion facilitates unconflicted motive expression, whereas introversion deflects social motives away from their characteristic goals and creates difficulties in goal attainment.

Adult↗
PubMed1998

Reversal of P-glycoprotein-mediated multidrug resistance by XR9051, a novel diketopiperazine derivative.

XR9051 (N-(4-(2-(6,7-Dimethoxy-1,2,3,4-tetrahydro-2-isoquinolyl)ethyl)phe nyl)-3-((3Z,6Z)-6-benzylidene-1-methyl-2,5-dioxo-3-pipera zinylidene) methylbenzamide) was identified as a potent modulator of P-glycoprotein-mediated multidrug resistance (MDR) following a synthetic chemistry programme based on a natural product lead compound. The activity of XR9051 was determined using a panel of human and murine drug-resistant cell lines (H69/LX4, 2780AD, EMT6/AR 1.0, MC26 and P388/DX Johnson). XR9051 was able to reverse resistance to a variety of cytotoxic drugs, including doxorubicin, etoposide and vincristine, which are associated with classical MDR. At a concentration of 0.3-0.5 microM, XR9051 was able to fully sensitize resistant cells to cytotoxics, whereas little or no effect was observed on the corresponding parental cell lines. No effect of XR9051 was observed on the response of cells to non-MDR cytotoxics such as methotrexate and 5-fluorouracil. XR9051 was consistently more potent than cyclosporin A (CsA) and verapamil (Vpm) in all assays used. XR9051 inhibited the efflux of [3H]daunorubicin from preloaded cells and, unlike CsA and Vpm, remained active for several hours after removal of resistance-modifying agent. In photoaffinity labelling experiments employing [3H]azidopine, XR9051 was able to displace binding to P-glycoprotein. In binding studies using [3H]vinblastine, XR9051 was shown to be a potent inhibitor of the binding of the cytotoxic to P-glycoprotein (EC50 = 1.4 +/- 0.5 nM). Taken together, the results indicate that XR9051 reverses the MDR phenotype through direct interaction with P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Safety, efficacy and cost-effectiveness of home therapy with recombinant activated factor VII in a patient with severe haemophilia A and an anti-factor VIII inhibitor.

We report the use of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) in a patient with severe haemophilia A and a high-titre anti-factor VIII inhibitor. A home therapy protocol was devised and its cost and efficacy were assessed after 2 years. rFVIIa (90 microg/kg) was self-administered at the onset of symptoms of bleeding. Doses were subsequently repeated at 2-h intervals until adequate haemostasis was achieved. The patient experienced a total of 25 bleeding episodes over the 2-year period, of which 23 were treated with up to three doses of rFVIIa. On two occasions, there was a recurrence of bleeding in the same area within 24 h, necessitating retreatment. There was a reduction in the number of inpatient hospital days compared with the 2 years before the use of rFVIIa and, overall, the cost of rFVIIa treatment was less than that of the previously used activated prothrombin complex concentrate (FEIBA; Immuno Ltd, Vienna, Austria). Our experience suggests that in selected haemophiliacs with inhibitors, home treatment with rFVIIa may be safe and cost-effective.

Cost-Benefit Analysis↗
PubMed1997

Predicting women's well-being in midlife: the importance of personality development and social role involvements.

Theories of adult development suggest that both personality and social roles are sources of adult well-being, but most research has examined only social roles. An integrated model was used, including personality, number of roles, and role quality, to predict well-being in 2 longitudinal studies of college-educated women. Results for both samples indicated that role quality and personality development were important components of the path to well-being, whereas number of roles, occupied was important mainly in early adulthood. Moreover, the results provided support for E. Erikson's (1968) notion of the importance of the sequencing of personality development for later well-being. Path analyses indicated that engagement in multiple roles during early adulthood facilitated the development of identity, which predicted generativity and role quality, which in turn predicted well-being.

Adaptation, Psychological↗
PubMed1997

Intracellular routing and inhibitory activity of oligonucleopeptides containing a KDEL motif.

On internalization, oligonucleotides (ODN) remain mostly sequestered in endocytic compartments. To increase their delivery into the cytosol and/or nucleus, which contain their targets, we attempted to guide them into compartments containing the KDEL receptor. Antisense ODN, phosphodiester protected at both ends, that are complementary to the AUG initiation site of gagHIV-1 mRNA (odn) were linked to a peptide ending with the Lys-Asp-Glu-Leu (KDEL) motif in a carboxyl-terminal position (odn-p-KDEL) or with the Lys-Asp-Glu-Ala (odn-p-KDEA) as a control. The effect of odn substitution with a peptide was examined with regard to its accumulation, subcellular location, and activity in HepG2 cells. Although odn-p-KDEL was internalized 4-fold less than the corresponding peptide-free odn, it was 5-fold more efficient in inhibiting gagHIV-1 gene expression in HepG2 cells. The internalization of odn-p-KDEA was as low as that of odn-p-KDEL, but its biological activity was lower, close to that of the peptide-free odn. On endocytosis at 37 degrees, both conjugates as well as the peptide-free odn were found in a neutral environment. However, the substitution of an odn with a KDEL motif altered its intracellular trafficking; most of the odn-p-KDEL was found in the endoplasmic reticulum and in the intermediate compartment as identified by colabeling with either anti-ERGIC-53 or anti-KDEL receptor antibodies. Conversely, odn-p-KDEA and peptide-free odn were localized in vesicular compartments not labeled with these antibodies. In addition, pulse-chase experiments showed that odn-p-KDEL and odn-p-KDEA had a lower efflux than peptide-free odn. Therefore, the large increase in efficiency was due to the KDEL motif.

Endocytosis↗
PubMed1996

Reduction of expression of the multidrug resistance protein (MRP) in human tumor cells by antisense phosphorothioate oligonucleotides.

Multidrug resistance protein (MRP) is a member of the ATP-binding cassette superfamily of transport proteins which has been demonstrated to cause multidrug resistance when transfected into previously sensitive cells. Sixteen eicosomeric oligonucleotides complementary to different regions along the entire length of the MRP mRNA reduced MRP mRNA and protein levels in drug-resistant small cell lung cancer cells that highly overexpress this protein. In MRP-transfected HeLa cells that express intermediate levels of MRP, one oligonucleotide, ISIS 7597, targeted to the coding region of the MRP mRNA, decreased the levels of MRP mRNA to < 10% of control levels in a concentration-dependent manner. This effect was rapid but transient with a return to control levels of MRP mRNA 72 hr after treatment. A double treatment with ISIS 7597 produced a sustained inhibition, resulting in a greater than 90% reduction in MRP mRNA for 72 hr and a comparable decrease in protein levels. Increased sensitivity to doxorubicin was observed under these conditions. Northern blotting analyses using two DNA probes corresponding to sequences 5' and 3' of the ISIS 7597 target sequence, respectively, revealed the presence of low levels of two smaller sized RNA fragments as expected from an RNase H-mediated mechanism of action of the antisense oligonucleotide. These studies indicate that a specific reduction in MRP expression can be achieved with antisense oligonucleotides, a finding that has potential implications for the treatment of drug-resistant tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Meanings of political participation among black and white women: political identity and social responsibility.

This study examined the correlates of midlife political participation among 64 Black and 107 White women of the college classes of 1967-1973. Compared with White women, Black women scored higher on political participation, generativity, power discontent, and politicization. Factor analysis of personality and political attitude variables yielded three factors labeled Political Identity, Power Discontent, and Social Responsibility. Adult political participation was regressed on level of student activism and index scores of political identity, power discontent, and social responsibility. For both racial groups, social responsibility was associated with midlife political participation. For White women, political identity was also related; for Black women, student activism bore a significant relationship. The findings suggest that Black and White women's historical and political contexts imbued their political activities with different meanings.

Adult↗
PubMed1996

Antecedents and contexts of generativity motivation at midlife.

A semiprojective measure of generativity motivation--the desire to contribute to the welfare of society--was developed and applied to a longitudinal sample of educated women. In support of previous theory that generativity represents a fusion of agency and communion, generativity at midlife was related to a combination of adolescent scores on achievement, affiliation, and power motivation. The measure was also related to independent indexes of generative wishes and Q-sort generativity. The importance of contextualizing generativity motivation is demonstrated: Generative women with careers found gratification through work, whereas generative women not working in careers experienced gratification through parenting. Generativity was also related to political consciousness. Finally, as young adults, generative women expressed gratitude toward mentors. The authors discuss theoretical implications for E. H. Erikson's (1950) concept of psychosocial generativity.

Achievement↗
PubMed1996

Effects of blockade of fast and slow inward current channels on ventricular fibrillation in the pig heart.

OBJECTIVE: To determine the contribution of fast and slow inward channels to the electrocardiogram (ECG) of ventricular fibrillation. METHODS: Ventricular fibrillation was induced by endocardial electrical stimulation in pigs anaesthetised with pentobarbitone sodium (30 mg/kg intravenously). ECGs simultaneously recorded from the body surface (lead II) and from the endocardium were studied by power spectrum analysis (0-40 Hz). RESULTS: The mean (SEM) dominant frequency of fibrillation (9.0 (1.1) Hz in lead II at 0-40 s) did not change significantly with time in pigs given intravenous saline. However, the dominant frequency was significantly reduced by intravenous pretreatment with the class I antiarrhythmic drugs, lignocaine (3 mg/kg, 6.5 (0.5) Hz; 10 mg/kg, 4.2 (0.6) Hz), mexiletine (3 mg/kg, 6.2 (0.4) Hz; 10 mg/kg, 5.5 (0.4) Hz), and disopyramide (2.5 mg/kg, 5.4 (0.6) Hz). After flecainide (3 mg/kg, 6.9 (0.5) Hz) the reduction in frequency was not significant. Similar data were obtained with endocardial recordings. In contrast pre-treatment with verapamil (0.2 mg/kg, 11.7 (0.8) Hz; and 1.0 mg/kg, 12.9 (1.6) Hz) produced a significantly higher dominant frequency of fibrillation than saline and widened the bandwidth of frequencies around the dominant frequency. CONCLUSIONS: These results indicate that voltage-dependent sodium channel currents contribute to the rapid frequencies of ventricular fibrillation. Blockade of L-type inward calcium channel activity increases the fibrillation frequency and fractionates the frequencies of the fibrillation wavefronts.

Animals↗
PubMed1996

Coronary artery stents.

The use of coronary stents to treat the acute complications of percutaneous transluminal coronary angioplasty and to reduce the restenosis rate following this procedure is reviewed.

Angioplasty, Balloon, Coronary↗
PubMed1996

Enhanced biological activity of antisense oligonucleotides complexed with glycosylated poly-L-lysine.

We sought to exploit glycosylated poly-L-lysine (pLK) to increase the uptake and biological antisense activity of a phosphorothioate oligonucleotide (pt-odn) [pt-odn complementary to the 3' noncoding region of intercellular adhesion molecule-1 (ICAM-1) (odn(ICAM-1))] complementary to the 3'-noncoding region of ICAM-1 in A549 cells. Dose-dependent inhibition of ICAM-1 expression was obtained (IC50 = 500 nM) through treatment of cells with odn(ICAM-1) complexed with pLK carrying fucose residues in the presence of 100 microM chloroquine. Alteration in the charge ratio between fucosylated pLK and pt-odn had a significant effect on the efficacy of inhibition (optimal conditions, charge ratio = 1.1). This effect was also dependent on the number of fucose moieties per pLK. Free pt-odn or pt-odn complexed with nonglycosylated pLK gave no inhibition at concentrations of < or = 2 microM. Two control pt-odn (one was targeted against an unrelated gene not present in these cells, gag(HIV), and the other had a randomized sequence) gave no inhibition of ICAM-1 expression in the presence or absence of pLK carrying fucose residues at concentrations of < or = 2 microM. When complexed with pLK carrying 100 fucose residues, the amount of cell-associated pt-odn was increased by 15-fold compared with the free pt-odn. Nongycosylated pLK also increased the amount of cell-associated pt-odn by >10 fold but did not alter the biological activity. These results demonstrate clearly the potential of glycosylated pLK as a pt-odn transporter.

Chloroquine↗