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Michelle Schmidt

Publications and source records attributed to Michelle Schmidt.

5 recordsLinked to original sources

Negative acting HLH proteins Id 1, Id 2, Id 3, and Id 4 are expressed in prostate epithelial cells.

BACKGROUND: The four known Id proteins, Id 1, Id 2, Id 3, and Id 4 are largely considered as dominant negative helix-loop-helix (HLH) proteins. They can dimerize with basic helix loop proteins (bHLH) but the dimers fail to bind the consensus E box response element (CANNTG). Alternatively, members of the Id family, for example, Id 2 can also bind to non-bHLH proteins such as retinoblastoma (Rb) and ETS-TCF to modulate their activities. Consistent with their role as promoters of proliferation, subset of Id genes for example, Id 1 and Id 2 are expressed in many cancers including that of the prostate. However, their expression and function in the normal prostate is unknown. METHODS: The present study was designed to evaluate the expression profile and functional significance of all Id isoforms in normal rat prostate epithelial cells. The data suggests that all four Id isoforms are expressed in normal cells, albeit at different levels. RESULTS: Agents that promote growth, for example, serum increase the levels of Id 1, Id 2, and Id 3. The hormones and mitogens such as testosterone and hepatocyte growth factor (HGF) that promote prostate epithelial cell differentiation stimulate Id 4 and Id 2, respectively. CONCLUSIONS: In prostate epithelial cells, Id 1 may be specifically involved in promoting proliferation whereas Id 4 and Id 2 may have defined roles in regulating differentiated functions in response to androgens and local paracrine factors such as HGF.

Animals↗

Radiolabeled RGD-DTPA-Tyr3-octreotate for receptor-targeted radionuclide therapy.

The aim of this study was to develop and investigate a radiopeptide for the treatment of cancers which overexpress cell surface somatostatin receptors. The new radiopharmaceutical is composed of a somatostatin receptor-targeting peptide, a chelator (DTPA) to enable radiolabeling, and an apoptosis-inducing RGD (arginine-glycine-aspartate) peptide moiety. The receptor-targeting peptide portion of the molecule, Tyr3-octreotate, is specific for the somatostatin subtype-2 cell surface receptor (sst2), which is overexpressed on many tumor cells. Because of the rapid endocytosis of the somatostatin receptor, the entire molecule can thus be internalized, allowing the RGD portion to activate intracellular caspases, which in turn promotes apoptosis. In this paper, we present the synthesis and the in vitro and in vivo tumor binding and internalization characteristics of this hybrid peptide. In vitro internalization into sst2-positive tumor cells of the radiolabeled hybrid peptide appeared to be a rapid process and could be blocked by an excess of unlabeled octreotide, indicating an sst2-specific process. Tumor uptake in vivo in rats of radiolabeled RGD-DTPA-Tyr3-octreotate was in agreein vitro data and similar to that of radiolabeled DOTA-Tyr3-octreotate. The combined molecule is expected to significantly enhance the therapeutic efficacy of the somatostatin-based agent.

Animals↗

Compromised emotional competence: seeds of violence sown early?

The authors expected less secure preschoolers to be less emotionally competent when interacting with peers at age 3 and that these emotionally incompetent children, especially those who showed much unregulated anger, would be less socially competent in kindergarten. These directional hypotheses were examined in a sample of 91 preschoolers, and all were corroborated.

Anger↗

Preschool understanding of emotions: contributions to classroom anger and aggression.

BACKGROUND: We sought to identify patterns of social cognitive differences among preschoolers that were related to risk of stable aggressive behavior with peers. Following Lemerise and Arsenio (2000), we considered the emotional components of early social cognition, reasoning that young children's substrate of emotion knowledge serves them in decoding social encounters. METHOD: One hundred and twenty-seven children from a longitudinal study from age 3 to 4 though to their kindergarten year were interviewed on their emotional knowledge initially using a puppet procedure and later with stories about mixed emotions and display rule. Each year their anger and antisocial responses to others' emotions were observed. Teachers also provided information on each child's anger and aggression. RESULTS: Children's deficits in emotion knowledge assessed at age 3 and 4 predicted subsequent years' aggression. This effect was especially pronounced for boys. CONCLUSIONS: The pattern of findings suggests that the processes implicated in Dodge's work with older children may begin earlier than previously thought, with a focus on emotions.

Aggression↗