Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adjuvanticity of MALP-2, a 2-kDa synthetic lipopeptide with macrophage-stimulatory activity, was evaluated in BALB/c mice using beta-galactosidase (beta-gal) as model antigen. When co-administered with beta-gal by either the intranasal (i.n.) or i.p. route, MALP-2 (0.5 microg) was capable of increasing beta-gal-specific serum IgG titers by 675-3,560-fold (i.n.) and 64-128-fold (i.p.), respectively, as compared to immunization with beta-gal alone. Using MALP-2, almost maximal IgG responses were already stimulated following the first immunization, and the IgG titers were similar to those observed using 10 microg of cholera toxin B subunit (CTB) as adjuvant. The mucosal immune system was also effectively stimulated (p<0.05) when MALP-2 was administered by the i.n. route (36% and 23% of beta-gal-specific IgA in lung and vaginal lavages, respectively). The i.n. co-administration of MALP-2 stimulated a stronger cellular immune response than CTB, both in submandibular lymph nodes and spleen (p<0.05). The analysis of beta-gal-specific IgG isotypes and the profiles of cytokines secreted by in vitro re-stimulated cells showed that co-administration of MALP-2 triggered a dominant Th2-response pattern. A recruitment of B220(+) and MAC-1(+) cells with an up-regulated expression of MHC class I, CD80 (B7.1) and CD54 (ICAM-1) was observed in nasal associated lymphoid tissues from MALP-2 treated mice. Taken together, our results demonstrated that the synthetic lipopeptide MALP-2 represents a very promising adjuvant for the mucosal delivery of vaccine antigens.
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PMID:The Mycoplasma-derived lipopeptide MALP-2 is a potent mucosal adjuvant. 1235 38

The majority of immunotherapy-based gene therapy protocols consist of ex vivo gene transfer in tumor cells. To prevent further in vivo growth, modified cells must be irradiated before reinjection into patients. The present study examines the effects of gamma-irradiation on transgene expression in transduced leukemic cells. Human and murine leukemic cells were transfected with retroviral vectors or plasmids carrying beta-galactosidase, GM-CSF or CD80 genes. Fresh leukemic cells from patients with acute myeloid leukemia (AML) were transfected with AdZ.F(pK7) adenoviral vector. gamma-irradiation at various lethal doses enhanced transgene expression in leukemic cell lines and fresh AML cells when the gene of interest was under CMV promoter but not when SV40 promoter was used. Oxidative stress also enhanced transgene expression and both irradiation and oxidative stress effects were inhibited by addition of N-acetyl-L-cysteine, a thiol anti-oxidant, indicating the involvement of reactive oxygen species. Transgene expression was also enhanced in vivo 48 and 120 h after subcutaneous injection of irradiated leukemic cells in syngeneic mice. These results show that a cell vaccine protocol using ex vivo gene transfer of transduced cells might be feasible in acute leukemia even if leukemic cells must be irradiated at lethal doses prior to reinjection to patients.
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PMID:Gamma-irradiation enhances transgene expression in leukemic cells. 1257 30

Intratracheal instillation of L-selectin-deficient (L-Sel(-/-)) mice with an adenovirus 2 (Ad2) vector resulted in the lack of respiratory Ad2- or beta-galactosidase-specific CTLs with concomitant long-lived beta-galactosidase transgene expression in the lungs. The absence of Ag-specific CTLs was attributed to a deficiency in lymphoid CD11c(+)CD8(+) dendritic cells (DCs) in the lower respiratory lymph nodes (LRLNs). To enable L-Sel(-/-) CTL activity, cell-sorted L-Sel(-/-)CD8(+) T cells were cocultured with cell-sorted L-Sel(+/+)CD8(+) or CD8(-) DCs or L-Sel(-/-)CD8(-) DCs. Only the CD8(+) DCs restored CTL activity; L-Sel(-/-)CD8(-) DCs failed to support L-Sel(+/+) CTLs because these remained immature, lacking the ability to express costimulatory molecules CD40, CD80, or CD86. Although no lung CD8(+) DCs were detected, the DC environment remained suppressive in L-Sel(-/-) mice evident by the lack of CTL responses following adenoviral challenge with OVA in recipient L-Sel(-/-) adoptively transferred with OT-1 CD8(+) T cells. To assess whether the L-Sel(-/-)CD8(-) DCs could be induced into maturity, microbial stimulation studies were performed showing the failure of L-Sel(-/-) LRLN to make matured DCs. When L-Sel(-/-) mice were subjected in vivo to microbial activation before Ad2 vector dosing, CTL activity was restored stimulating the renewed presence of LRLN CD8(+) DCs in L-Sel(-/-) mice. These studies show that impairment of L-Sel(-/-) DC maturation results in insufficient mature DCs that require microbial activation to restore increases in respiratory CD8(+) DCs to support CTL responses.
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PMID:The absence of lymphoid CD8+ dendritic cell maturation in L-selectin-/- respiratory compartment attenuates antiviral immunity. 1860 89


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