Heart disease and the resultant heart failure is one of the leading causes of death in the world. Although advances in treating heart failure have improved patient outcomes, the morbidity and mortality of the disease still remains high. Based on the finding that up-regulation of brain natriuretic peptide (BNP) is a biomarker of heart failure, which can be a result of abnormal stretch of cardiomyocytes, in this thesis, we attempted to make adenoviral reporter constructs using BNP promoter that is activated upon mechanical stretch to establish a basis for gene transfer therapy for heart failure. Using a mechanical device to mimic abnormal stretch of cardiomyocytes, we investigated the stretch-induced expression of several reporter constructs, which contained different combinations of regulatory sequences (GATA4, M- CAT and Nkx2-5) known to be involved in stretch-induced BNP expression. Our study concluded that among those reporter constructs we prepared, only GATA4-containing construct showed significant level of expression with up- regulation of 1.57 fold upon stretch. Although such result from this has much to be improved, the identification of stretch-inducible artificial gene construct will serve as an important framework to let us focus on increasing the degree of up-regulation for clinical applications

Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50 % of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling, and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Anti-Retroviral Treatment Effects Research Study, CHARTER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (r = -0.24; p = 0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance.