Long-term occlusal and soft-tissue profile outcomes after treatment of Class II Division 1 malocclusion with fixed appliances

Introduction: Our objective was to determine which factors were predictive of good long-term outcomes after fixed appliance treatment of Class II Division 1 malocclusion. Methods: Two hundred seven patients with Class II Division 1 malocclusion were examined in early adulthood at a mean of 4.6 years after treatment with fixed appliances. The peer assessment rating index was used to evaluate dental alignment and occlusal relationships. The soft-tissue profile was assessed with the Holdaway angle. Results: Logistic regression identified 3 pretreatment variables that were predictive of a good facial profile (Holdaway angle) at recall: the lower lip to E-plane distance (P

Claudin-1 Has Tumor Suppressive Activity and Is a Direct Target of RUNX3 in Gastric Epithelial Cells

BACKGROUND & AIMS: The transcription Factor RUNX3 is a gastric tumor suppressor. Tumorigenic Runx3(-/-) gastric epithelial cells attach weakly to each other, compared with nontumorigenic Runx3(+/+) cells. We alined to identify RUNX3 target genes that promote cell-cell contact to Improve our understanding of RUNX3's role in Suppressing gastric carcinogenesis. METHODS: We compared gene expression profiles of Runx3(+/+) and Runx3(-/-) cells and observed down-regulation of genes associated with cell-cell adhesion in Runx3(-/-) cells. Reporter, mobility shift, and chromatin immunoprecipitation assays were used to examine the regulation of these genes by RUNX3. Tumorigenesis assays and immunohistologic, analyses of human gastric tumors were performed to confirm the role of the candidate genes ill gastric tumor development. RESULTS: Mobility shift and chromatin immunoprecipitation assays revealed that the promoter activity of the gene that encodes the tight Junction protein claudin-1 was up-regulated via the binding of RUNX3 to the RUNX consensus sites. The tumorigenicity of gastric epithelial cells From Runx3(-/-) mice was significantly reduced by restoration of claudin-1 expression, whereas knockdown of claudin-1. increased the tumorigenicity of human gastric cancer cells. Concomitant expression of RUNX3 and claudin-1 was observed in human normal gastric epithelium and cancers. CONCLUSIONS: The tight junction protein claudin-1 has gastric tumor suppressive activity and is a direct transcriptional target of RUNX3. Claudin-1 is down-regulated during the epithelial-mesenchymal transition; RUNX3 might therefore act as a tumor suppressor to antagonize the epithelial-mesenchymal transition.

Llama antibody fragments have good potential for application as HIV-1 topical microbicides

There is an urgent global need for preventative strategies against HIV-1 infections. Llama heavy-chain antibody fragments (VHH) are a class of molecules recently described as potent cross-clade HIV-1 entry inhibitors. We studied the potential of a VHH-based microbicide in an application-oriented fashion. We show that VHH can be inexpensively produced in high amounts in the GRAS organism S. cerevisiae, resulting in very pure, and endotoxin free product. VHH are very stable under conditions they might encounter during transport, storage or use by women. We developed active formulations of VHH in aqueous gel and compressed and lyophilized tablets for controlled release from an intra vaginal device. The release profile of the VHH from e.g. a vaginal ring suggests sufficient bioavailability and protective concentration of the molecule at the mucosal site at the moment of the infection. The ex vivo penetration kinetics through human tissues show that the VHH diffuse into the mucosal layer and open the possibility to create a second defense layer either by blocking the HIV receptor binding sites or by blocking the receptors of immune cells in the mucosa. In conclusion, our data show that VHH have

Cytotoxicity of 1-alkylquinolinium bromide ionic liquids in murine fibroblast NIH 3T3 cells

Minimal toxicity data are available for 1-alkylquinolinium bromide ionic liquids. Here, their toxicity to NIH 3T3 murine fibroblast cells, of relevance to their potential antimicrobial application, is presented. Toxicity data, presented by time-point analysis with a particular focus on the immediate toxicity upon short term cellular exposure, indicate a link between the length of the alkyl chain substituent and resultant biological toxicity. 1-Tetradecylquinolinium bromide was found to exhibit cellular toxicity comparable to benzalkonium chloride over all time points tested. By comparison, 1-octylquinolinium bromide initially exerted significantly lower cytotoxicity at one hour; however, toxicity was found to have a cumulative effect over time-course analysis up to three days. This illustrates that alkyl chain components may govern not only overall toxicity, but also the rate of toxicity. Fluorescence microscopy was utilised to examine destabilisation of the plasma membrane by 1 tetradecylquinolinium bromide and benzalkonium chloride after one hour, with membrane destabilisation not observed for 1-octylquinolinium bromide, or the base constituent quinoline.

Connective tissue growth factor antagonizes transforming growth factor-beta 1/Smad signalling in renal mesangial cells

The critical involvement of TGF-beta 1 (transforming growth factor-beta 1) in DN (diabetic nephropathy) is well established. However, the role of CTGF (connective tissue growth factor) in regulating the complex interplay of TGF-beta 1 signalling networks is poorly understood. The purpose of the present study was to investigate co-operative signalling between CTGF and TGF-beta 1 and its physiological significance. CTGF was determined to bind directly to the T beta RIII (TGF-beta type III receptor) and antagonize TGF-beta 1-induced Smad phosphorylation and transcriptional responses via its N-terminal half. Furthermore, TGF-beta 1 binding to its receptor was inhibited by CTGF. A consequent shift towards non-canonical TGF-beta 1 signalling and expression of a unique profile of differentially regulated genes was observed in CTGF/TGF-beta 1-treated mesangial cells. Decreased levels of Smad2/3 phosphorylation were evident in STZ (streptozotocin)-induced diabetic mice, concomitant with increased levels of CTGF Knockdown of T beta RIII restored TGF-beta 1-mediated Smad signalling and cell contractility, suggesting that T beta RIII is key for CTGF-mediated regulation of TGF-beta 1. Comparison of gene expression profiles from CTGF/TGF-beta 1-treated mesangial cells and human renal biopsy material with histological diagnosis of DN revealed significant correlation among gene clusters. In summary, mesangial cell responses to TGF-beta 1 are regulated by cross-talk with CTGF, emphasizing the potential utility of targeting CTGF in DN.

A charged-particle microbeam .1. Development of an experimental system for targeting cells individually with counted particles

Charged-particle microbeams provide a unique opportunity to control precisely, the dose to individual cells and the localization of dose within the cell. The Gray Laboratory is now routinely operating a charged-particle microbeam capable of delivering targeted and counted particles to individual cells, at a dose-rate sufficient to permit a number of single-cell assays of radiation damage to be implemented. By this means, it is possible to study a number of important radiobiological processes in ways that cannot be achieved using conventional methods. This report describes the rationale, development and current capabilities of the Gray Laboratory microbeam.

Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.