A qualitative study of the experiences of people who identify themselves as having adjusted positively to a visible difference

Individual and group interviews explored experiences of positive adjustment among 12 people with a range of visible differences. Thematic analysis identified four main themes: importance of appearance; personal growth; relationships with others; and coping (factors in the coping theme considered to be paramount to positive adjustment were inner strength and positivity, active coping techniques, downward social comparisons, taking things day-by-day, spirituality and humour). The findings provide insight into behaviours and personal outlooks that may contribute to adaptive coping and have implications for future research and interventions aimed at those who exhibit poor adjustment to visible difference. The article reflects on the use of both individual and group interviews for research in this field.     

Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor that plays a key role in the differentiation of adipocytes. Activation of this receptor in liposarcomas and breast and colon cancer cells also induces cell growth inhibition and differentiation. In the present study, we show that PPARgamma is expressed in human prostate adenocarcinomas and cell lines derived from these tumors. Activation of this receptor with specific ligands exerts an inhibitory effect on the growth of prostate cancer cell lines. Further, we show that prostate cancer and cell lines do not have intragenic mutations in the PPARgamma gene, although 40% of the informative tumors have hemizygous deletions of this gene. Based on our preclinical data, we conducted a phase II clinical study in patients with advanced prostate cancer using troglitazone, a PPARgamma ligand used for the treatment of type 2 diabetes. Forty-one men with histologically confirmed prostate cancer and no symptomatic metastatic disease were treated orally with troglitazone. An unexpectedly high incidence of prolonged stabilization of prostate-specific antigen was seen in patients treated with troglitazone. In addition, one patient had a dramatic decrease in serum prostate-specific antigen to nearly undetectable levels. These data suggest that PPARgamma may serve as a biological modifier in human prostate cancer and its therapeutic potential in this disease should be further investigated.     

Endothelial monocyte activating polypeptide II induces endothelial cell apoptosis and may inhibit tumor angiogenesis

Endothelial monocyte activating polypeptide II (EMAP-II) is a tumor-derived cytokine with potent effects on endothelial cells in vitro and in vivo including upregulation of tissue factor and the sensitization of human melanoma to systemic TNF treatment via its effects on the tumor vasculature. We investigated the effects of EMAP-II on tumor growth, angiogenesis, vasculogenesis, and apoptosis. EMAP-II inhibited endothelial cell proliferation, vasculogenesis, and neovessel formation. In vivo growth of human melanoma lines expressing high amounts of EMAP-II demonstrated slower growth, smaller tumors, and increased amounts of tumor necrosis than those expressing lower amounts of EMAP-II. EMAP-II induced endothelial-cell-specific apoptosis via a pathway that includes upregulation of the Fas-associated death domain and downregulation of Bcl-2. EMAP-II appears to have important effects on angiogenesis and may play a role in regulating tumor vascular growth.     

The Intermediate lactotroph: a morphologically distinct, ghrelin-responsive pituitary cell in the dwarf (dw/dw) rat

Profound somatotroph hypoplasia in the dwarf (dw/dw) rat is accompanied by an estrogen-dependent induction of prolactin secretion by the GH secretagogue, GHRP-6. Using electron microscopy, we demonstrated that the reduction in the somatotroph population in the dw/dw pituitary is accompanied by the presence of a morphologically distinct lactotroph subpopulation. In these cells, which did not coexpress GH, the size, shape, and number of the secretory granules were between those of the type I and type II lactotrophs. We therefore called these cells intermediate lactotrophs. The intermediate lactotrophs accounted for up to 30% of the total prolactin-positive cell population in dw/dw males and up to 12% in females. Using tannic acid to quantify the fusion of secretory granules, we have shown that the intermediate lactotrophs are unresponsive to either GH-releasing factor (GRF) or TRH but exhibit a sexually dimorphic secretory response to acute ghrelin treatment, granular fusions being 4-fold higher in females. No cell matching the morphology of the novel lactotroph subpopulation was observed in the pituitary of the GRF-insensitive lit/lit mouse. However, ablation of GRF neurons with neonatal monosodium glutamate treatment had no effect on the population of intermediate lactotrophs in the dw/dw rat. Thus, the presence of the intermediate lactotrophs in the dw/dw pituitary appears to be independent of the function of the GRF neurons.     

Design, synthesis, and evaluation of novel biarylpyrimidines: a new class of ligand for unusual nucleic acid structures

Biarylpyrimidines are characterized as selective ligands for higher-order nucleic acid structures. A concise and efficient synthesis has been devised incorporating Suzuki biaryl cross-coupling of dihalopyrimidines. Two ligand series are described based on the parent thioether 4,6-bis[4-[[2-(dimethylamino)ethyl]mercapto]phenyl]pyrimidine (1a) and amide 4,6-bis(4[(2-(dimethylamino)ethyl)carboxamido]phenyl)pyrimidine (2a) compounds. In UV thermal denaturation studies with the poly(dA) x [poly(dT)]2 triplex structure, thioethers showed stabilization of the triplex form (Delta Tm < or = 20 degrees C). In contrast, amides showed duplex stabilization (Delta Tm < or = 15 degrees C) and either negligible stabilization or specific destabilization (Delta Tm = -5 degrees C) of the triplex structure. Full spectra of nucleic acid binding preferences were determined by competition dialysis. The strongest interacting thioether bound preferentially to the poly(dA) x [poly(dT)]2 triplex, K(app) = 1.6 x 10(5) M(-1) (40 x K(app) for CT DNA duplex). In contrast, the strongest binding amide selected the (T2G20T2)4 quadruplex structure, K(app) = 0.31 x 10(5) M(-1) (6.5 x K(app) for CT DNA duplex).