Targeting and detecting cancer cells using spontaneously formed multifunctional dendrimer-stabilized gold nanoparticles.

We develop a facile approach to fabricating multifunctional dendrimer-stabilized gold nanoparticles (Au DSNPs) for cancer cell targeting and imaging. In this work, amine-terminated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers pre-functionalized with folic acid (FA) and fluorescein isothiocyanate (FI) are complexed with Au(III) ions, followed by acetylation of the amine groups on the dendrimer surfaces. This one-step process leads to the spontaneous formation of 6 nm-sized Au nanoparticles stabilized by multifunctional dendrimers bearing both targeting and imaging functionalities.

Multifunctional dendrimer-modified multiwalled carbon nanotubes: synthesis, characterization, and in vitro cancer cell targeting and imaging.

Carbon nanotubes hold great promise for their use as a platform in nanomedicine, especially in drug delivery, medical imaging, and cancer targeting and therapeutics. Herein, we present a facile approach to modifying carbon nanotubes with multifunctional poly(amidoamine) (PAMAM) dendrimers for cancer cell targeting and imaging. In this approach, fluorescein isothiocyanate (FI)- and folic acid (FA)-modified amine-terminated generation 5 (G5) PAMAM dendrimers (G5·NH(2)-FI-FA) were covalently linked to acid-treated multiwalled carbon nanotubes (MWCNTs), followed by acetylation of the remaining primary amine groups of the dendrimers.

Tumor necrosis factor-related apoptosis-inducing ligand inhibits experimental autoimmune thyroiditis by the expansion of CD4+CD25+ regulatory T cells.

There have been several reports that TNF-related apoptosis-inducing ligand (TRAIL) has the ability to suppress the development of experimental autoimmune diseases, including a mouse model of experimental autoimmune encephalomyelitis, a rabbit model of rheumatoid arthritis, type 1 diabetes mellitus, in mice and experimental autoimmune thyroiditis (EAT) in mice. However, the mechanism underlying TRAIL effect is not well defined. In the present study, we specifically examined TRAIL effects on CD4(+)CD25(+) regulatory T cells.

Microarray analysis of cytokine activation of apoptosis pathways in the thyroid.

It has been suggested that Fas-mediated apoptosis plays an important role in the pathogenesis of autoimmune thyroid diseases. Our previous studies have demonstrated that normal primary thyroid epithelial cells are resistant to Fas-mediated apoptosis, but the resistance can be overcome by pretreatment with a combination of interferon-gamma (IFN-gamma) and IL-1beta. To understand the molecular mechanism responsible for the IFN-gamma/IL-1beta effects, we profiled changes in the transcription induced by these two cytokines in normal human thyroid cells, using cDNA microarrays.

Dendrimer-entrapped gold nanoparticles as a platform for cancer-cell targeting and imaging.

We present a general approach for the targeting and imaging of cancer cells using dendrimer-entrapped gold nanoparticles (Au DENPs). Au DENPs were found to be able to covalently link with targeting and imaging ligands for subsequent cancer-cell targeting and imaging. The Au DENPs linked with defined numbers of folic acid (FA) and fluorescein isothiocyanate (FI) molecules are water soluble, stable, and biocompatible.

Death ligand tumor necrosis factor-related apoptosis-inducing ligand inhibits experimental autoimmune thyroiditis.

The role of TNF-related apoptosis-inducing ligand (TRAIL) in autoimmune thyroiditis is unclear. We used experimental autoimmune thyroiditis to clarify the contribution of TRAIL to the development of autoimmune thyroiditis. CBA/J mice were immunized with murine thyroglobulin, and spleen cells from these mice were subsequently injected into irradiated recipient CBA/J mice.

Direct and distinguishable inhibitory roles for SUMO isoforms in the control of transcriptional synergy.

Functional interactions between factors bound at multiple sites on DNA often lead to a synergistic or more-than-additive transcriptional response. We previously defined a class of peptide sequences termed synergy control motifs (SC motifs) that function in multiple regulators by selectively inhibiting synergistic activity driven from multiple but not single response elements. By studying the prototypic SC motifs of the glucocorticoid receptor, we show that SC motifs inhibit transcription per se both in cis and in trans, and that a requirement for multiple contacts with DNA renders them selective for compound response elements.

Use of flow cytometry to quantify mouse gastric epithelial cell populations.

Flow cytometry provides the opportunity to quantify cell populations within a total cell suspension. The quality of flow cytometry is strongly dependent on the isolation of intact viable cells. However, techniques to isolate mouse gastric cells for flow cytometry have not been evaluated.

An OmpA-like protein from Acinetobacter spp. stimulates gastrin and interleukin-8 promoters.

Bacterial overgrowth in the stomach may occur under conditions of diminished or absent acid secretion. Under these conditions, secretion of the hormone gastrin is elevated. Alternatively, bacterial factors may directly stimulate gastrin.

Library faculty role in problem-based learning: facilitating small groups.

Since 1986, the library faculty of the McGoogan Library of Medicine at the University of Nebraska Medical Center (UNMC) has participated in small group activities during the week-long orientation for first-year medical students. This involvement paved the way for library faculty members to act as facilitators for small groups of medical students within the new problem-based learning (PBL) curriculum introduced in 1992 by the College of Medicine. The UNMC curriculum consists of traditional PBL groups as well as Integrated Clinical Experience (ICE) small groups.

A point mutation in the MyoD basic domain imparts c-Myc-like properties.

MyoD and c-Myc, members of the large "basic-helix-loop-helix" family of proteins, regulate diverse aspects of both normal and neoplastic growth and specific gene regulation. These two proteins differ at 9 of the 14 amino acids that comprise the basic domains necessary for DNA binding and transcriptional control. Individual amino acids in the MyoD basic domain were mutated to those found at the analogous positions in c-Myc.

Regulation of the junB gene by v-src.

The proteins encoded by cellular and viral src genes are believed to be involved in the transmission of mitogenic signals, the nuclear recipients of which are largely unknown. In this work, we report that four different v-src-transformed cell lines from three different species possess elevated levels of junB transcripts. Transient expression of junB promoter-chloramphenicol acetyltransferase constructs in NIH 3T3 cells was used to demonstrate that the increase in junB transcripts was specifically associated with v-src expression and could not be recapitulated with a c-src, v-H-ras, or v-raf expression vector.

Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.

Complete hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency causes the Lesch-Nyhan syndrome, an X-linked, purine metabolism disorder manifested by hyperuricemia, hyperuricaciduria, and neurologic dysfunction. Partial HPRT deficiency causes hyperuricemia and gout. One requirement for understanding the molecular basis of HPRT deficiency is the determination of which amino acids in this salvage enzyme are necessary for structural or catalytic competence.