Generation and characterization of the humoral immune response to DNA immunization with a chimeric beta-amyloid-interleukin-4 minigene

Active immunization with fibrillar beta-amyloid peptide (AB42) as well as passive transfer of anti-AB antibodies significantly reduces AB plaque deposition, neuritic dystrophy, and astrogliosis in the brain of mutant amyloid precursor protein (APP)-transgenic mice. Although the mechanism(s) of clearance of AB from the brain following active or passive immunization remains to be determined, it is clear that anti-AB antibodies are critical for clearance. DNA immunization provides an attractive alternative to direct peptide and adjuvant approaches for inducing a humoral response to AB. We constructed a DNA minigene with AB fused to mouse interleukin-4 (pAB42-IL-4) as a molecular adjuvant to generate anti-AB antibodies and enhance the Th2-type of immune responses. Gene gun immunizations induced primarily IgG1 and IgG2b anti-AB antibodies. Fine epitope analysis with overlapping peptides of the AB42 sequence identified the 1- 15 region as a dominant B cell epitope. The DNA minigeneinduced anti-AB antibodies bound to AB plaques in brain tissue from an Alzheimer's disease patient demonstrating functional activity of the antibodies and the potential for therapeutic efficacy. Originally published European Journal of Immunology, Vol. 33, No. 12, Dec 200

Estimation of cancer incidence and mortality attributable to alcohol drinking in china

Background. Cancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005. Methods. We calculated the proportion of cancers attributable to alcohol use to estimate the burden of alcohol-related cancer. The population attributable fraction was calculated based on the assumption of no alcohol drinking. Data on alcohol drinking prevalence were from two large-scale national surveys of representative samples of the Chinese population. Data on relative risk were obtained from meta-analyses and large-scale studies. Results. We found that a total of 78,881 cancer deaths were attributable to alcohol drinking in China in 2005, representing 4.40% of all cancers (6.69% in men, 0.42% in women). The corresponding figure for cancer incidence was 93,596 cases (3.63% of all cancer cases). Liver cancer was the main alcohol-related cancer, contributing more than 60% of alcohol-related cancers. Conclusions. Particular attention needs to be paid to the harm of alcohol as well as its potential benefits when making public health recommendations on alcohol drinking. \ua9 2010 Liang et al; licensee BioMed Central Ltd

Bisbibenzyls, a New Type of Antifungal Agent, Inhibit Morphogenesis Switch and Biofilm Formation through Upregulation of DPP3 in Candida albicans

The yeast-to-hypha transition plays a crucial role in the pathogenesis of C. albicans. Farnesol, a quorum sensing molecule (QSM) secreted by the fungal itself, could prevent the formation of hyphae and subsequently lead to the defect of biofilm formation. The DPP3, encoding phosphatase, is a key gene in regulating farnesol synthesis. In this study, we screened 24 bisbibenzyls and 2 bibenzyls that were isolated from bryophytes or chemically synthesized by using CLSI method for antifungal effect. Seven bisbibenzyls were found to have antifungal effects with IC80 less than 32 µg/ml, and among them, plagiochin F, isoriccardin C and BS-34 were found to inhibit the hyphae and biofilm formation of C. albicans in a dose-dependent manner. To uncover the underlying relationship between morphogenesis switch and QSM formation, we measured the farnesol production by HPLC-MS and quantified Dpp3 expression by detecting the fluorescent intensity of green fluorescent protein tagged strain using Confocal Laser Scanning microscopy and Multifunction Microplate Reader. The DPP3 transcripts were determined by real-time PCR. The data indicated that the bisbibenzyls exerted antifungal effects through stimulating the synthesis of farnesol via upregulation of Dpp3, suggesting a potential antifungal application of bisbibenzyls. In addition, our assay provides a novel, visual and convenient method to measure active compounds against morphogenesis switch

Using NHANES oral health examination protocols as part of an esophageal cancer screening study conducted in a high-risk region of China

<p>Abstract</p> <p>Background</p> <p>The oral health status of rural residents in the People's Republic of China has not been extensively studied and the relationship between poor oral health and esophageal cancer (EC) is unclear. We aim to report the oral health status of adults participating in an EC screening study conducted in a rural high-risk EC area of China and to explore the relationship between oral health and esophageal dysplasia.</p> <p>Methods</p> <p>National Health and Nutrition Examination Survey (NHANES) oral health examination procedures and the Modified Gingival Index (MGI) were used in a clinical study designed to examine risk factors for esophageal cancer and to test a new esophageal cytology sampling device. This study was conducted in three rural villages in China with high rates of EC in 2002 and was a collaborative effort involving investigators from the National Institutes of Health and the Cancer Institute of the Chinese Academy of Medical Sciences.</p> <p>Results</p> <p>Nearly 17% of the study participants aged 40–67 years old were edentulous. Overall, the mean number of adjusted missing teeth (including third molars and retained dental roots) was 13.8 and 35% had 7 contacts or less. Women were more likely to experience greater tooth loss than men. The average age at the time of first tooth loss for those with no posterior functional contacts was approximately 41 years for men and 36 years for women. The mean DMFT (decayed, missing, and filled teeth) score for the study population was 8.5. Older persons, females, and individuals having lower educational attainment had higher DMFT scores. The prevalence of periodontal disease (defined as at least one site with 3 mm of attachment loss and 4 mm of pocket depth) was 44.7%, and 36.7% of the study participants had at least one site with 6 mm or more of attachment loss. Results from a parsimonious multivariate model indicate that participants with poor oral health wemore likely to have esophageal dysplasia (OR = 1.59; 95% CI 1.06, 2.39).</p> <p>Conclusion</p> <p>This report describes the first use of NHANES oral health protocols employed in a clinical study conducted outside of the United States. The extent and severity of poor oral health in this Chinese study group may be an important health problem and contributing factor to the prevalence of EC.</p

Anti-inflammatory and healing action of oral gel containing borneol monoterpene in chemotherapy-induced mucositis in rats ( Rattus norvegicus )

ABSTRACT The aim of this study was to investigate the effect of gels containing the monoterpene borneol in induced oral mucositis using an animal model. Gels were prepared with borneol at 1.2% and 2.4% (w/w). Oral mucositis was induced by administration of three doses of 5-fluorouracil (30 mg/kg, i.p.) and injury with acetic acid (50%, v/v) soaked in filter paper applied to right cheek mucosa for 60s. Four subgroups comprising 12 animals each were formed. Six animals from each group were sacrificed at days seven and fourteen after oral mucositis induction. Mucous samples were processed and stained with hematoxylin-eosin and Masson’s Trichrome. The semiquantitative evaluation involved observation of inflammatory parameters. ImageJ® software was used in the quantitative evaluation. For statistical analyses, Two-way ANOVA, followed by Tukey’s post-test (p <0.05), were employed. Borneol 2.4% gel proved effective in the treatment of oral mucositis with statistically significant differences between groups for angiogenesis control, inflammatory cell count reduction and percentage neoformed collagen increase. The confirmation of anti-inflammatory and healing action of borneol in oral mucositis in rats renders it a good marker for predicting this activity for plant extracts rich in this substance

Does a Manufacturer Benefit from Selling to a Better-Forecasting Retailer?

This paper considers a manufacturer selling to a newsvendor retailer that possesses superior demand-forecast information. We show that the manufacturer's expected profit is convex in the retailer's forecasting accuracy: The manufacturer benefits from selling to a better-forecasting retailer if and only if the retailer is already a good forecaster. If the retailer has poor forecasting capabilities, then the manufacturer is hurt as the retailer's forecasting capability improves. More generally, the manufacturer tends to be hurt (benefit) by improved retailer forecasting capabilities if the product economics are lucrative (poor). Finally, the optimal procurement contract is a quantity discount contract.supply chain contracting, asymmetric information, forecasting