http://hdl.handle.net/2144/967 2013-05-22T00:22:07Z http://hdl.handle.net/2144/3332 Risk of Tooth Loss After Cigarette Smoking Cessation Krall Kaye, Elizabeth; Dietrich, Thomas; Nunn, Martha E; Garcia, Raul I INTRODUCTION. Little is known about the effect of cigarette smoking cessation on risk of tooth loss. We examined how risk of tooth loss changed with longer periods of smoking abstinence in a prospective study of oral health in men. METHODS. Research subjects were 789 men who participated in the Veterans Administration Dental Longitudinal Study from 1968 to 2004. Tooth status and smoking status were determined at examinations performed every 3 years, for a maximum follow-up time of 35 years. Risk of tooth loss subsequent to smoking cessation was assessed sequentially at 1-year intervals with multivariate proportional hazards regression models. Men who never smoked cigarettes, cigars, or pipes formed the reference group. Hazard ratios were adjusted for age, education, total pack-years of cigarette exposure, frequency of brushing, and use of floss. RESULTS. The hazard ratio for tooth loss was 2.1 (95% confidence interval [CI], 1.5-3.1) among men who smoked cigarettes during all or part of follow-up. Risk of tooth loss among men who quit smoking declined as time after smoking cessation increased, from 2.0 (95% CI, 1.4-2.9) after 1 year of abstinence to 1.0 (95% CI, 0.5-2.2) after 15 years of abstinence. The risk remained significantly elevated for the first 9 years of abstinence but eventually dropped to the level of men who never smoked after 13 or more years. CONCLUSION. These results indicate that smoking cessation is beneficial for tooth retention, but long-term abstinence is required to reduce the risk to the level of people who have never smoked. 2006-09-15T00:00:00Z http://hdl.handle.net/2144/3333 Activin A Expression Regulates Multipotency of Mesenchymal Progenitor Cells Djouad, Farida; Jackson, Wesley M; Bobick, Brent E; Janjanin, Sasa; Song, Yingjie; Huang, George TJ; Tuan, Rocky S INTRODUCTION. Bone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); however, comparable adult progenitor or stem cells have also been isolated from a wide variety of tissues. This study aims to assess the functional similarities of MPCs from different tissues and to identify specific factor(s) related to their multipotency. METHODS. For this purpose, we directly compared MPCs isolated from different adult tissues, including bone marrow, tonsil, muscle, and dental pulp. We first examined and compared proliferation rates, immunomodulatory properties, and multidifferentiation potential of these MPCs in vitro. Next, we specifically evaluated activin A expression profile and activin A:follistatin ratio in MPCs from the four sources. RESULTS. The multidifferentiation potential of the MPCs is correlated with activin A level and/or the activin A:follistatin ratio. Interestingly, by siRNA-mediated activin A knockdown, activin A was shown to be required for the chondrogenic and osteogenic differentiation of MPCs. These findings strongly suggest that activin A has a pivotal differentiation-related role in the early stages of chondrogenesis and osteogenesis while inhibiting adipogenesis of MPCs. CONCLUSIONS. This comparative analysis of MPCs from different tissue sources also identifies bone marrow-derived MPCs as the most potent MPCs in terms of multilineage differentiation and immunosuppression, two key requirements in cell-based regenerative medicine. In addition, this study implicates the significance of activin A as a functional marker of MPC identity. 2010-05-04T00:00:00Z http://hdl.handle.net/2144/3328 The Jacob2 Lectin of the Entamoeba Histolytica Cyst Wall Binds Chitin and Is Polymorphic Ghosh, Sudip K.; Van Dellen, Katrina L.; Chatterjee, Anirban; Dey, Tuli; Haque, Rashidul; Robbins, Phillips W.; Samuelson, John BACKGROUND. The infectious and diagnostic form of Entamoeba histolytica (Eh), cause of amebic dysentery and liver abscess, is the quadranucleate cyst. The cyst wall of Entamoeba invadens (Ei), a model for Eh, is composed of chitin fibrils and three sets of chitin-binding lectins that cross-link chitin fibrils (multivalent Jacob lectins), self-aggregate (Jessie lectins), and remodel chitin (chitinase). The goal here was to determine how well the Ei model applies to Entamoeba cysts from humans. METHODS/RESULTS. An Eh Jacob lectin (EhJacob2) has three predicted chitin-binding domains surrounding a large, Ser-rich spacer. Recombinant EhJacob2 made in transfected Eh trophozoites binds to particulate chitin. Sequences of PCR products using primers flanking the highly polymorphic spacer of EhJacob2 may be used to distinguish Entamoeba isolates. Antibodies to the EhJacob2, EhJessie3, and chitinase each recognize cyst walls of clinical isolates of Entamoeba. While numerous sera from patients with amebic intestinal infections and liver abscess recognize recombinant EhJacob1 and EhJessie3 lectins, few of these sera recognize recombinant EhJacob2. CONCLUSIONS/SIGNIFICANCE. The EhJacob2 lectin binds chitin and is polymorphic, and Jacob2, Jessie3, and chitinase are present in cyst walls of clinical isolates of Entamoeba. These results suggest there are substantial similarities between cysts of the human pathogen (Eh) and the in vitro model (Ei), even though there are quantitative and qualitative differences in their chitin-binding lectins. Author SummaryFor many years, we and others have used cysts of Entamoeba invadens (Ei), a reptilian parasite, to model the infectious and diagnostic cysts of the human pathogen Entamoeba histolytica (Eh). The Ei cyst wall is composed of chitin fibrils, as well as Jacob and Jessie lectins that have unique chitin-binding domains. Our recent results suggest a "wattle and daub" model of the Ei cyst wall, where the wattle or sticks (chitin fibrils bound by multivalent Jacob lectins) is constructed prior to the addition of the mortar or daub (self-aggregating Jessie3 lectins). Here we "humanize" the Ei model of the cyst wall with four findings. First, a recombinant Eh Jacob2 lectin, which has three predicted chitin-binding domains surrounding a large spacer domain, binds chitin beads. Second, polymorphisms in the spacer domain of EhJacob2 discriminate clinical isolates of Entamoeba. Third, chitinase, Jacob2 lectin, and Jessie3 lectin are present in cyst walls of clinical isolates of Entamoeba. Finally, numerous sera from patients infected with Entamoeba recognize recombinant Eh Jacob1 and Jessie3 lectins. 2010-07-20T00:00:00Z http://hdl.handle.net/2144/3329 Toll-Like Receptor-2 Mediates Diet and/or Pathogen Associated Atherosclerosis: Proteomic Findings Madan, Monika; Amar, Salomon BACKGROUND. Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE+/- mice. METHODS AND RESULTS. To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE+/--TLR2+/+, ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 μl live Porphyromonas gingivalis (P.g) (107 CFU) or vehicle (normal saline). Animals were euthanized 24 weeks after the first inoculation. ApoE+/--TLR2+/+ mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE+/--TLR2+/+ mice were significantly higher than from ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE+/--TLR2+/+ mice compared to ApoE+/--TLR2+/- and TLR2-/- mice, irrespective of diet or bacterial challenge. ApoE+/--TLR2+/+ mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist) also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE+/--TLR2-/- mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS) of aortic samples analyzed by 2-dimentional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE+/--TLR2+/+ mice fed the high fat diet and inoculated with P.g compared to any other group. CONCLUSION. Genetic deficiency of TLR2 reduces diet- and/or pathogen-associated atherosclerosis in ApoE+/- mice, along with differences in plaque composition suggesting greater structural stability while TLR-2 ligand-specific activation triggers atherosclerosis. The present data offers new insights into the pathophysiological pathways involved in atherosclerosis and paves the way for new pharmacological interventions aimed at reducing atherosclerosis. 2008-09-12T00:00:00Z