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Background: The purpose of this study was to investigate how educational status influences cardiovascular risk factors and care of diabetes mellitus and hypertension. Methods: From Korean National Health and Nutrition Survey IV, we obtained survey results of 6,835 men and 9,067 women more than 30 years old. We performed multivariate logistic regression to compare cardiovascular risk factors and care of hypertension and diabetes respective to educational status. Results: There were disparities in cardiovascular risk factors by educational status. In men, impaired fasting glucose, high triglyceride, and smoking were less frequently found in the highest educated group than in the middle educated group. In women, the prevalence of abdominal obesity, impaired fasting glucose, high blood pressure, high triglyceride, and metabolic syndrome among the highest educated group were significantly lower. The proportion of those with proper physical activity in the highest educated group was found to be less than that of the middle educated group, regardless of gender. For care of diabetes mellitus and hypertension, disease recognition and treatment were lower among the lowest educated group in men, while these disparities were not shown in women. Instead, the lowest educated group in diabetic women received screening exams for eye and kidney complications less than the middle education group. In both genders, the high education group had a higher chance of receiving education about diabetes mellitus. Conclusion: There were educational disparities in cardiovascular risk factors and care of hypertension and diabetes mellitus. The disparities were found to be different by gender.

Oncolytic adenoviral vectors are currently being developed as biologic anticancer agents. Coupling the lytic function of an oncolytic adenovirus (Ad) with its ability as a transgene delivery system represents a powerful extension of this methodology. A clear advantage is the amplification of a therapeutic gene, as replicating vectors would be able to infect and deliver the gene of interest to neighboring cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the most potent stimulators of a specific and long-lasting antitumor immunity and its important role in the maturation of antigen-presenting cells to induce T-cell activation has been well documented. Similarly, the B7 family has also been shown to play an integral role in mediating an antitumor response. Most tumor cells, however, lack the expression of these costimulatory molecules on their surface, thus escaping immune system recognition. To increase the antitumor effect of an oncolytic Ad, we have generated an E1B 55 kDa-deleted oncolytic adenoviral vector, YKL-GB, that expresses both GM-CSF and B7-1. The therapeutic efficacy of YKL-GB Ad was evaluated in immunocompetent mice bearing murine melanoma B16-F10 tumors. Significant inhibition of tumor growth was seen in mice treated with YKL-GB compared to those treated with the analogous vector, YKL-1. Moreover, YKL-GB oncolytic Ad demonstrated enhanced antitumor activity and higher incidences of tumor regression compared to a replication-incompetent Ad, dl-GB, which coexpresses GM-CSF and B7-1. Localized GM-CSF and B7-1 gene transfer also conferred long-lasting immunity against a tumor re-challenge. To establish that the observed antitumor effect is associated with the generation of a tumor-specific immune response, we carried out interferon-gamma enzyme-linked immune spot assay. We observed that YKL-GB induced significantly higher immune cell activation than YKL-1. Furthermore, immunohistochemical studies demonstrated robust dendritic cells and CD4(+)/CD8(+) T-cell infiltration in these mice compared to the YKL-1-treated groups. In agreement with these results, splenocytes from tumor-bearing mice treated with YKL-GB expressed high levels of the costimulatory and activation molecules. These findings demonstrate the effectiveness of enhancing the immune response against tumors with an oncolytic Ad expressing both GM-CSF and B7-1 and provide a potential therapeutic strategy for the management of neoplasia.

Adenovirus (Ad) has been genetically modified to exhibit various functions. The replication competent adenovirus is exemplary, being used as an effective anti-tumor agent in cancer gene therapy. Two E1B-mutant adenovirus strains, Ad-ΔE1B, Ad-ΔE1B55, have been previously developed, both of which undergo selective replication in cancer cells, ultimately killing them. The E1B 55kDa-deleted adenovirus Ad-ΔE1B55 replicates selectively in tumor cells with dysfunctional tumor suppressor gene p53. On the other hand, the E1B 19kDa protein was shown to confer anti-apoptotic function, possibly repressing inherent apoptosis in tumor cells. Ad-ΔE1B, with both its E1B 19kDa and E1B 55kDa deleted, showed, in addition to tumor-selective replication, a supplemental anti-tumor effect, allowing apoptosis in the tumor cells. Recently, the application of replication competent adenovirus in combination with radiotherapy or chemotherapy has shown optimistic preclinical and clinical trial results. In this study, we evaluated Ad-ΔE1B or Ad-ΔE1B55-mediated cytotoxicity in combination with irradiation treatment. Hepatocellular carcinoma (Hep3B), lung cancer (A549), and cervical cancer (C33A) cell lines were treated, in vitro, with Ad-ΔE1B or Ad-ΔE1B55, followed by irradiation treatment. The highest cytotoxicity was observed in cancer cell lines treated with Ad-ΔE1B and irradiation. Apoptosis was synergistically increased in cancer cell lines treated with Ad-ΔE1B and irradiation, demonstrated by flow cytometry and TUNEL assay. Established C33A xenografts were treated with 108 plaque forming unit (PFU) of Ad-ΔE1B or Ad-ΔE1B55, in conjunction with 10 Gray (Gy) of single fraction local tumor radiation. Individually, Ad-ΔE1B, Ad-ΔE1B55, and 10 Gy irradiation caused moderate decrease in tumor size, and after 31 days, the tumors were 44.2%, 76.3%, and 36.9%, in volume (mm3), respectively. In contrast, a sharp decrease in tumor size was observed when the adenovirus treatment was combined with 10 Gy irradiation; at 31 days, the tumor was measured 10.0% and 18.9% in size respectively. Overall, this study presents strong evidence for a synergistic effect when treatment of E1B-mutant adenovirus strains is combined with irradiation exposure.

Detecting any presence of retroviruses in biological material is important to ensure safety and prevent retroviral infection, which has been associated with various disorders including malignancies, immunodeficiencies, and neurological disorders. Highly specific and sensitive PCR techniques are used to detect specifically the presence of a known retrovirus. In contrast, the presence of an unknown retrovirus can only be examined by non-specific methods such as transmission electron microscopy and growth of virus on susceptible cells. However, detection methodologies involving cell culture techniques may be ineffective because certain retroviruses are not cytopathic in vitro. Retroviruses possess RNA-dependent DNA polymerase known as reverse transcriptase (RT), which is inherent in all kinds of retrovirus. Taking advantage of its ubiquitous nature in retroviruses, enzymatic activity of RT may be measured to detect retroviral contamination in biological products. On the basis of the polymerase enhanced reverse transcriptase (PERT) assay, two different assay systems, PCR-based RT assay (PERT-PCR) and ELISA-based RT assay (PERT-ELISA), were developed. Respective optimum conditions were determined. Sensitivity, linearity and reproducibility of the methods were studied on purified RT. Both PERT-PCR and PERT-ELISA could detect as little as 10-10 unit/ml of RT. Nonetheless, no additional increase in sensitivity was observed by performing ELISA after PCR amplification. Treatment with RNase after cDNA synthesis increased sensitivity over 100 times, and the addition of synthetic DNA competitors, which suppress RT-like activities of cellular DNA-dependent DNA polymerases, greatly increased specificity of the assay. A modified form of PERT-PCR assay was used and subsequently RT activities were detected in vaccines and culture supernatant of retrovirus-producing cells. This enhanced form of PERT-PCR assay is easy to perform and is able to detect up to 10-10 unit/ml of purified RT, as well as RT in vaccines and cell culture supernatant. Thus, this study presents an enhanced assay, applicable to screening of all replication-competent retrovirus, quantification of the viral load, drug susceptibility testing of RT, and control of virus inactivation in biological products.