1995 — 1997 |
Xu, Weidong |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cocaine/Gender Interactive Effects On Immune Function @ University of Tennessee Health Sci Ctr
The proposed research employs a mouse model to investigate the effects of cocaine on immune function with an emphasis on possible sex-type differences. The proposal is prompted by: 1) the high incidence of cocaine abuse; 2) the high incidence of AIDS and other infections in cocaine abusers; 3) the absence of a systematic literature on the effects of cocaine on immune function; 4) an even more conspicuous absence of literature on the interactions of cocaine with sex-type and age; and, 5) our preliminary findings that cocaine attenuated Con-A and PHA induced T cell proliferation, the latter at a lower dose in female than male mice. The proposed hypotheses are that acute cocaine exposure will attenuate the immune response; that the attenuation will be greater in female than male mice; that the attenuation will be greater during estrus than diestrus; that the attenuation will be greater in young adult than prepuberal mice; that the gender difference will be greater in young adult than prepuberal mice; and that repeated cocaine injections will produce dose dependent increases in T, B, and NK cell function and decreases in macrophage activity. Our studies will thus systematically examine the effects of varying cocaine dosage and time after drug exposure on the function of T cells, B cells, NK cells, and macrophage in 35-day-old and 60-day-old male and female mice. The proposed studies differ from previous work in several ways. First, the experiments include both male and female mice, thus will establish whether sex-type influences the immune response to cocaine. Use of the two sexes will provide information about whether previous studies completed on males might generalize to females. Second, by including prepuberal and adult groups, the interactions of cocaine, age, and sex-type on immune function will be addressed. Third, the proposed studies provide an initial investigation into the possible influence of estrus state on the effects of cocaine on immune system. Fourth, the study includes dose-response and time course data for both acute and repeated exposure. Finally, four major immunocompetent cell types will be examined under a common exposure condition. This systematic assessment may help resolve some of the conflicting information in extant literature. These studies will fill voids in the basic science literature on the effects of cocaine on immune function particularly in females, and may provide important information relevant to the clinical manifestations of cocaine abuse.
|
0.912 |
2002 |
Xu, Weidong |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core--Molecular Biology Facility @ Dana-Farber Cancer Institute
Development of prophylactic strategies to prevent infection of HIV-1 requires a suitable virus/animal model Chimeric simian-human immunodeficiency viruses (SHIVs) have been shown to productively infect non-human primates and to induce AIDS-like disease in infected animals. To test prophylactic strategies against HIV-1 clade C in vivo (Projects 2 and 3), the construction of a chimeric SHIV that expresses and HIV-1 clade C envelope from a primary patient isolate as essential. DNA-based vaccines, with their ability to express antigens in vivo, represent a new approach to protect against AIDS virus infections. DNA vaccines are able to raise humoral and cell-mediated immune responses against HIV. Thus, we propose to construct a recombinant DNA vaccine expressing HIV-1 clade C env, and to test its ability in vivo to raise a protective immune response (Project 3). Other retrovirusal infections (SRV/D, STLV-I) can confound experiments with SHIV. Core B will screen all experimental animals (Projects 2 and 3) for these viruses. Plasma viral RNA load is a key parameter in disease progression of lentiviral infection. We have developed a very sensitive real-time RT-PCR in our laboratory that will be used to monitor viral plasma kinetics in experimental animals (Projects 2 and 3). In addition, DNA pro-viral loads will be quantified by DNA PCR in experimental animals. The overall goal of Core B is to provide molecular biology expertise and support for projects 2 and 3: (1) Generation of chimeric SHIV containing env of a recently transmitted pediatric HIV-1 clade C isolate (SHIVenvC) (2) Generation of plasmids expressing codon-optimized HIV-1 clade C env and SIV gag-pol (3) Monitoring of experimental animals for other retrovirus infections (4) Monitoring of viral kinetics of SHIVenvC
|
0.904 |
2008 |
Xu, Weidong |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Targeted Delivery of Sirna Nanoparticles to Prevent Hiv-1 Transmission @ Transgenex Nanobiotech, Inc.
[unreadable] DESCRIPTION (provided by applicant): According to estimates by the Joint United Nations Program on HIV/AIDS (UNAIDS), approximately 40 million people will be living with HIV/AIDS worldwide by the end of 2006. However, safe and effective AIDS vaccine remains difficult to develop. Small interference RNA (siRNA) has emerged as a powerful tool in gene silencing, and appears promising in treatment of viral infections and cancers. The combination of siRNA and chitosan nanoparticle technology led to the development nanocomplex antivirals capable of inhibiting respiratory syncytial virus infections (Zhang et. al. Nature Medicine, 2005). Based on the preliminary in vitro data for suppressing HIV replication, it is hypothesized that siRNA nanocomplexes comprise a potential therapeutic approach against AIDS. The long-term goal of our proposal is to develop multifunctional siRNA nanoparticles to protect HIV transmission. However, we will only test the antiviral activities of the multifunctio intensified, since a safe and effective AIDS vaccine remains difficult to develop and won't be available in this decade. Small interfering RNA (siRNA) has emerged as a powerful tool in gene silencing, and preclinical studies have shown promise in treatment of viral infection and cancer. The potential of siRNA for inhibiting respiratory infections has been demonstrated using a nanoparticle delivery system in a mouse model of respiratory syncytoial virus (RSV) infection. Intranasal treatment before or after RSV infection with nanoparticles containing siRNA targeting the NS1 gene of RSV showed substantially decreased virus titers in the lung and decreased inflammation and airway reactivity compared to controls. These results have led to the working hypothesis that multifunctional chitosan nanoparticles (MCNs) can effectively deliver siRNA without any significant adverse effects and provide significant protection against viral infections, specifically HIV. The specific aims of this proparticles in inhibiting SHVSF163P3 replication in human or monkey peripheral blood mononuclear leukocytes (PBMCs). In vitro confirmation of the antiviral activity of the multifunctional siRNA nanoparticles will ensure the success in future studies in non-human primates. The proposed project is significant, successful delivery of anti-HIV siRNA nanoparticles to prevent HIV-1 replication in vitro will help us in non-human primate studies or preclinical trials in the future. Thus, the novel chitosan nanoparticle drug delivery system will be useful not only in AIDS research but also in studies in cancer and other diseases [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable][unreadable]
|
0.901 |