Distinctive molecular composition of human gingival interdental papilla.

BACKGROUND: Gingiva is composed of attached and marginal (free) gingiva and interdental papilla. Increasing esthetic demands in dentistry have created a need to restore all parts of the gingiva. However, the interdental papilla has limited regeneration potential compared to other parts of the gingiva. It also is more susceptible to gingival overgrowth, suggesting that it has distinct cellular and molecular properties from other parts of the gingiva. Very little is known about the possible differences in the molecular composition of different parts of the gingiva. METHODS: We compared the expression of a set of key molecules in interdental papilla and marginal gingiva from seven healthy subjects by immunohistochemical staining. RESULTS: In the interdental papilla, immunoreactivity for integrin alphavbeta6 and cytokeratin 19 in the oral epithelium was significantly higher than in marginal gingiva. Expression of type I procollagen, extra domain A (EDA) and extra domain B (EDB) fibronectin isoforms, tenascin-C, transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), and the signaling molecule son-of-sevenless (SOS)-1 also were increased in the interdental papilla. The expression of small leucine-rich proteoglycans decorin, biglycan, fibromodulin, and lumican in the interdental papilla was partially different from the marginal gingiva. CONCLUSIONS: Molecular composition of the interdental papilla is distinct from marginal gingiva. Increased expression of molecules normally induced in wound healing (alphavbeta6 integrin, fibronectin-EDB and -EDA, tenascin-C, type I procollagen, TGF-beta, CTGF, and SOS-1) suggests that the cells in the interdental papilla are in an activated state and/or inherently display a specific phenotype resembling wound healing.

Amidine analogue of chlorambucil is a stronger inhibitor of protein and DNA synthesis in breast cancer MCF-7 cells than is the parent drug.

A novel amidine analogue of chlorambucil-N-(2-(4-(4-bis(2-chloroethyl)aminophenyl)butyryl)aminoethyl)-5-(4-amidinophenyl)-2-furancarboxamide hydrochloride (AB(1)) and the parent drug were compared for their effects on collagen and DNA biosynthesis in breast cancer MCF-7 cells. IC(50) values for chlorambucil and AB(1) for collagen biosynthesis were found to be about 33 and 13 microM, respectively. The greater potency of AB(1) to suppress collagen synthesis was found to be accompanied by a stronger compared with chlorambucil inhibition of prolidase activity and expression. The phenomenon was related to inhibition of beta(1)-integrin and IGF-I receptor-mediated signaling caused by this compound. The expression of beta(1)-integrin receptor, as well as Src, son of sevenless protein (SOS) and phosphorylated mitogen activated protein (MAP) kinases (MAPK), extracellular-signal-regulated kinase 1 (ERK(1)) and kinase 2 (ERK(2)) but not focal adhesion kinase pp125(FAK) (FAK), Shc, and Grb-2 was significantly decreased in cells incubated for 24 h with 10 microM AB(1) compared to the control, whereas in the same conditions chlorambucil did not evoke any changes in expression of all these signaling proteins, as shown by Western immunoblot analysis. Furthermore, AB(1) induced a stronger down-regulation of the expression of IGF-I receptor and evoked a higher antiproliferative effect. During 12 and 24 h of incubation AB(1) decreased DNA biosynthesis by about 33 % and 51 % of the control, whereas chlorambucil decreased it by about 19 % and 35 %, respectively. These data suggest that the amidine analogue of chlorambucil is a stronger inhibitor of protein and DNA synthesis in MCF-7 cells than is the parent drug.

Neuron-specific mRNA complexity responses during hippocampal apoptosis after traumatic brain injury.

In an effort to understand the complexity of genomic responses within selectively vulnerable regions after experimental brain injury, we examined whether single apoptotic neurons from both the CA3 and dentate differed from those in an uninjured brain. The mRNA from individual active caspase 3(+)/terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling [TUNEL(-)] and active caspase 3(+)/TUNEL(+) pyramidal and granule neurons in brain-injured mice were amplified and compared with those from nonlabeled neurons in uninjured brains. Gene analysis revealed that overall expression of mRNAs increased with activation of caspase 3 and decreased to below uninjured levels with TUNEL reactivity. Cell type specificity of the apoptotic response was observed with both regionally distinct expression of mRNAs and differences in those mRNAs that were maximally regulated. Immunohistochemical analysis for two of the most highly differentially expressed genes (prion and Sos2) demonstrated a correlation between the observed differential gene expression after traumatic brain injury and corresponding protein translation.