Biomedical subjects

A D Powell

Publications and source records attributed to A D Powell.

5 recordsLinked to original sources

PubMed2006

Hypoxia- and radiation-activated Cre/loxP 'molecular switch' vectors for gene therapy of cancer.

Although a significant negative prognostic factor, tumor hypoxia can be exploited for gene therapy. To maximize targeting within the tumor mass, we have developed synthetic gene promoters containing hypoxia-responsive elements (HREs) from the erythropoietin (Epo) gene as well as radiation-responsive CArG elements from the early growth response (Egr) 1 gene. Furthermore, to achieve high and sustained expression of the suicide gene herpes simplex virus thymidine kinase (HSVtk), our gene therapy vectors contain an expression amplification system, or 'molecular switch', based on Cre/loxP recombination. In human glioma and breast adenocarcinoma cells exposed to hypoxia and/or radiation, the HRE/CArG promoter rapidly activated Cre recombinase expression leading to selective and sustained HSVtk synthesis. Killing of transfected tumor cells was measured after incubation with the prodrug ganciclovir (GCV; converted by HSVtk into a cytotoxin). In vitro, higher and more selective GCV-mediated toxicity was achieved with the switch vectors, when compared with the same inducible promoters driving HSVtk expression directly. In tumor xenografts implanted in nude mice, the HRE/CArG-switch induced significant growth delay and tumor eradication. In conclusion, hypoxia- and radiation-activated 'molecular switch' vectors represent a promising strategy for both targeted and effective gene therapy of solid tumors.

Adenocarcinoma↗

PubMed2001

The medication life.

The therapist conducting psychodynamic psychotherapy often recommends medication for the patient, but the medication is frequently treated as separate from the therapy and not worth exploring. By not inviting the patient's and our own feelings about medication into the treatment dialogue, we may solicit the development of split transference, the loss of important unconscious material, and noncompliance. Much like a patient's dream life, the medication life is rich in detail that may be fruitfully used to gain information about the patient's experience, strengthen the alliance, and improve treatment outcome.

Adult↗

PubMed2000

P2Y purinoceptors inhibit exocytosis in adrenal chromaffin cells via modulation of voltage-operated calcium channels.

We have used combined membrane capacitance measurements (C(m)) and voltage-clamp recordings to examine the mechanisms underlying modulation of stimulus-secretion coupling by a G(i/o)-coupled purinoceptor (P2Y) in adrenal chromaffin cells. P2Y purinoceptors respond to extracellular ATP and are thought to provide an important inhibitory feedback regulation of catecholamine release from central and sympathetic neurons. Inhibition of neurosecretion by other G(i/o)-protein-coupled receptors may occur by either inhibition of voltage-operated Ca(2+) channels or modulation of the exocytotic machinery itself. In this study, we show that the P2Y purinoceptor agonist 2-methylthio ATP (2-MeSATP) significantly inhibits Ca(2+) entry and changes in C(m) evoked by single 200 msec depolarizations or a train of 20 msec depolarizations (2.5 Hz). We found that P2Y modulation of secretion declines during a train such that only approximately 50% of the modulatory effect remains at the end of a train. The inhibition of both Ca(2+) entry and DeltaC(m) are also attenuated by large depolarizing prepulses and treatment with pertussis toxin. Inhibition of N-type, and to lesser extent P/Q-type, Ca(2+) channels contribute to the modulation of exocytosis by 2-MeSATP. The Ca(2+)-dependence of exocytosis triggered by either single pulses or trains of depolarizations was unaffected by 2-MeSATP. When Ca(2+) channels were bypassed and exocytosis was evoked by flash photolysis of caged Ca(2+), the inhibitory effect of 2-MeSATP was not observed. Collectively, these data suggest that inhibition of exocytosis by G(i/o)-coupled P2Y purinoceptors results from inhibition of Ca(2+) channels and the Ca(2+) signal controlling exocytosis rather than a direct effect on the secretory machinery.

Adenosine Triphosphate↗

PubMed1995

Racial differences in women's desires to be thin.

The goal of this research was to attempt to understand why white women are more prone to develop eating disorders than black women. Using self-reports, we found that white women chose a significantly thinner ideal body size than did black women, and expressed more concern than black women with weight and dieting. White women also experienced greater social pressure to be thin than did black women. White men indicated less desire than black men to date a women with a heavier than ideal body size, and white men felt they would more likely be ridiculed than did black men if they did date a woman who was larger than the ideal. The results suggest that black women experience eating disorders less than white women at least in part because they experience less pressure to be thin.

Black or African American↗

PubMed1991

Flow cytometric characterization and sorting of cultured Brassica napus microspores.

A flow cytometric procedure was used to characterize and sort embryogenic Brassica napus microspore cultures. Embryogenic microspores continued to increase in size throughout the culture period and fluoresced when stained with fluoresecein diacetate (FDA). However, most of the cells in culture (greater than 95%) lost their viability over the culture period and the correlation between the percentage viable cells in a culture and the productivity of the culture was not significant until day 3. By sorting large fluorescent cells on day 1 and day 3 of the culture period populations of cells that were 7-18-fold more embryogenic than sorted mixed cells were obtained. The flow cytometric procedure would be useful for rapidly assessing the effects of a large variety of culture and media conditions on embryogenesis is rapeseed microspore cultures. Furthermore, the populations of potentially embryogenic microspores isolated by flow cytometry might be useful for studies of the early cellular and molecular changes that occur during androgenesis in rapeseed.

Brassica↗