Search PubMed⌕ Search

Biomedical subjects

J D Boyer

Publications and source records attributed to J D Boyer.

43 records · Page 3Linked to original sources
PubMed1994

Immunotherapeutic strategies targeting rheumatoid synovial T-cell receptors by DNA inoculation.

Immunotherapy against autoreactive T-cell receptors (TCRs) has been reported to have promise in several animal models of autoimmune diseases. Facilitated DNA inoculation has many potential advantages as a modality for development of specific immune responses. Specifically, this technology is able to deliver exogenous antigens for processing via both the endogenous pathway, with subsequent presentation by class-I major histocompatibility (MHC) antigens, and the exogenous pathway, with subsequent presentation by class-II MHC antigens. This allows for induction of both arms of the cellular immune system. These cellular immune responses may be particularly important in targeting and controlling pathogenic cell populations. The application of this technology to the treatment of human autoimmune diseases depends on the availability of readily manipulated systems for the evaluation of specific interventions. Here we report the full length cloning and expression of TCRs from rheumatoid arthritis synovial tissue. These were developed by recombinant polymerase chain reaction, cloning and retroviral transduction into a TCR-alpha/beta-negative murine T-cell hybridoma. Reconstitution of CD3 expression was confirmed by flow cytometry. Similar constructs have been developed for TCR-based immunotherapy by facilitated inoculation of DNA intramuscularly. Preliminary analysis of immune responses in mice indicates that these constructs elicit anti-TCR responses. These studies indicate the ability to reconstitute expression of potentially autoreactive human TCRs in a model system wherein specific immune responses elicited against these TCRs by various immunogens can be evaluated.

Amino Acid Sequence↗
PubMed1994

Postoperative alopecia: a case report and literature review.

Postoperative alopecia is the temporary or permanent loss of hair that occurs following prolonged immobilization during general anesthesia and intubation. The clinical and histopathologic aspects of a typical case are described and the literature reviewed. Localized pressure-induced ischemia is the likely cause. Patients at highest risk for permanent hair loss include those subject to cardiac or gynecologic surgical procedures where the combined intraoperative and postoperative intubation time exceeds twenty-four hours. Frequent intraoperative and postoperative head repositioning provides excellent prophylaxis.

Aged↗
PubMed1993

Genetic infection induces protective in vivo immune responses.

Drug-induced abortive retroviral infection has been reported to induce both T-cell and B-cell immunity in vivo. We sought to analyze if replication-incompetent retroviruses could induce the development of similarly protective in vivo immune responses in a more desirable fashion. To evaluate retroviral transduction vaccination (genetic infection), a plasmid encoding human CD4 in a retroviral vector was transfected into the pA317 amphotropic retroviral packaging system. The resulting replication defective retrovirus was used to transduce BALB/c mice prior to tumor challenge with human CD4. Immunization elicited specific humoral and cellular anti-human CD4 responses. We evaluated anti-cell responses using a tumor model system. We observed that BALB/c mice challenged with SP2/0 lymphoma cells develop lethal tumors and die within 7 weeks of challenge. Cloned SP2/0 cells stably transfected with the human cell-surface antigen CD4 also develop tumors in naive mice and succumb to the tumors in a similar manner to SP2/0 inoculated animals. In contrast, CD4 retrovirus-transduced animals, when challenged with the CD4-expressing SP2/0 cells, demonstrated a low incidence of tumors and significantly enhanced survival compared to the mice immunized similarly with human CD8 retrovirus. These results establish an in vivo tumor challenge system with relevance to the development of protective in vivo immune responses, and indicate that genetic infection is a useful technique for inducing protective immunity.

Animals↗
PubMed1992

Transport regulation of recombinant gene expression in E. coli and B. subtilis.

Expression kinetics of the lactose (lac) operon in Escherichia coli are reviewed for both wild-type and recombinant cell cultures under chemostatic conditions. A unified model which involves regulation of active inducer (lactose) transport, promoter-operator regulated expression of the lac operon, glucose-mediated inducer exclusion, and catabolite repression is summarized and supporting data is shown to verify its accuracy. The synthesis of alpha-amylase with a recombinant form of Bacillus subtilis is also reviewed to point out generic features in transport regulation, the lac operon model providing a point of departure. While there are many similarities in the influence of transport on both regulating models, there are also important differences. In a chemostat system, the synthesis of alpha-amylase is nongrowth associated, while beta-galactosidase is a growth-associated enzyme. Nevertheless, transport regulation is an important feature in both instances.

Journal Article↗
PubMedDate not supplied

Next generation DNA vaccines for HIV-1.

We studied the effects of first generation HIV-1 plasmid vaccines in 167 individuals. The vaccines were very well tolerated and induced helper T cell responses in most vaccine recipients. However, the CTL responses were below a 20% response rate. Improvement in vaccine potency is an important goal of this technology and a central focus of our laboratory. To improve on these response rates, we used RNA optimized constructs pGag and pEnv). These vaccines express 20-100 fold better than first generation vectors. However, our studies support that additional enhancements are needed to further boost the immune response. We report that we can significantly enhance the induced CD8 effector cell response by including engineered B7 costimulatory molecules. We observed that B7.2 was more effective at driving cellular immune responses than B7.1 as a plasmid vaccine. We developed gene swaps and deletions between these two molecules. This manipulation resulted in a dramatically enhanced cellular immune response as measured by CTL, or ICC or Elispot. We have also explored the use of cytokines as plasmid vaccine adjuvants. We observed that IL-12 and IL-15 were effective as plasmid vaccine adjuvants. Interestingly, IL-15 appeared to allow T cell expansion in the absence of significant T cell help. Improvement of the immune response induced by plasmid vaccines can be engineered in multiple ways. Our studies show that both costimulation as well as cytokine signals can be harnessed for more potent vaccine development. These results have important implications for the design of vaccines for prophylaxis and therapy.

AIDS Vaccines↗
PubMedDate not supplied

Safety and immunogenicity of intramuscular and intravaginal delivery of HIV-1 DNA constructs to infant chimpanzees.

Any global strategy for controlling the human immunodeficiency virus (HIV) epidemic is likely to rely heavily on immunization of infants and children. Given the well-documented differences in children's responses to traditional vaccines, we initiated this study to extend our findings on DNA vaccination of adult chimpanzees to immunologically immature infant chimpanzees. Our findings were consistent with our previous work in adults as we observed that the DNA vaccines used here were both well tolerated and immunogenic within weeks of the initial vaccination.

AIDS Vaccines↗