| 1. |
- Qazi, K. R., et al.
(författare)
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Enhancement of DNA vaccine potency by linkage of Plasmodium falciparum malarial antigen gene fused with a fragment of HSP70 gene
- 2005
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 23:9, s. 1114-1125
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Tidskriftsartikel (refereegranskat)abstract
- Finding an appropriate adjuvant for human vaccination is crucial. HSPs have been shown to act as adjuvants when coadministered with peptide antigens or given as fusion proteins. However, there is a potential risk of autoimmunity when using the complete molecules because HSPs are evolutionary conserved. To overcome this. we first evaluated the adjuvant effect of a less conserved fragment of Plasmodium falciparum HSP70 (Pf70C) as compared it to that of the whole HSP70 molecule from Trypanosoma cruzi (TcHSP70). We found that Pf70C exhibited similar adjuvant properties as the whole molecule. We then evaluated the adjuvant potential of Pf70C for the malarial antigen EB200 in a chimeric DNA construct. No appreciable levels of EB200 specific antibodies were detected in mice immunized with the DNA constructs only. However, the DNA immunization efficiently primed the immune system, as indicated by the strong Th-1 antibody response elicited by a subsequent boosting with the corresponding recombinant fusion proteins. In contrast, while no such priming effect was observed for ex vivo IFN-gamma production, stimulation with the HSP chimeric fusion protein induced an enhanced secretion of IFN-gamma in vitro as compared to other proteins used. Our results emphasize the potential of HSPs as adjuvants in subunit vaccines.
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| 2. |
- Qazi, Mousumi R, et al.
(författare)
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High-dose, short-term exposure of mice to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) affects the number of circulating neutrophils differently, but enhances the inflammatory responses of macrophages to lipopolysaccharide (LPS) in a similar fashion.
- 2009
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Ingår i: Toxicology. - : Elsevier BV. - 1879-3185 .- 0300-483X. ; 262:3, s. 207-14
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Tidskriftsartikel (refereegranskat)abstract
- Having found previously that high-dose, short-term dietary exposure of mice to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) suppresses adaptive immunity, in the present study we characterize the effects of these fluorochemicals on the innate immune system. Male C57BL/6 mice receiving 0.02% (w/w) PFOS or PFOA in their diet for 10 days exhibited a significant reduction in the numbers of total white blood cells (WBC), involving lymphopenia in both cases, but neutropenia only in response to treatment with PFOA. Moreover, both compounds also markedly reduced the number of macrophages (CD11b(+) cells) in the bone marrow, but not in the spleen or peritoneal cavity. The ex vivo production of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) by peritoneal macrophages isolated from animals treated with PFOA or PFOS was increased modestly. Moreover, both fluorochemicals markedly enhanced the ex vivo production of these same cytokines by peritoneal and bone marrow macrophages stimulated either in vitro or in vivo with lipopolysaccharide (LPS); whereas there was no such effect on splenic macrophages. The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by prior exposure to PFOA, but not by PFOS. None of these parameters of innate immunity were altered in animals receiving a dietary dose of these compounds that was 20-fold lower (0.001%, w/w). These findings reveal that in addition to suppressing adaptive immunity, high-dose, short-term exposure of mice to either PFOS or PFOA augments inflammatory responses to LPS, a potent activator of innate immunity.
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| 3. |
- Qazi, S. Junaid S., et al.
(författare)
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Use of wide-angle X-ray diffraction to measure shape and size of dispersed colloidal particles
- 2009
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 338:1, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory X-ray diffraction is used to investigate the size and shape of dispersed plate-like and spherical colloidal particles. Analysis of the wide-angle diffraction data provides information about the size and shape of crystals from the width of the Bragg peaks according to the Debye-Scherrer formula. The measurements, data analysis, and evaluation are discussed. It is shown that X-ray diffraction with conventional laboratory equipment on dispersed particles is feasible as a tool to determine both particle size and shape. Data for two samples - gold colloids and nickel (II) hydroxide particles are presented. The advantages and limitations of the method are discussed. X-ray diffraction measurements that are made in combination with dynamic light scattering can be used to estimate the thickness of stabilizing layers of polymers. (C) 2009 Elsevier Inc. All rights reserved.
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| 4. |
- Scherfer, Christoph, et al.
(författare)
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The Toll immune-regulated Drosophila protein Fondue is involved in hemolymph clotting and puparium formation
- 2006
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Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 295, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Clotting is critical in limiting hemolymph loss and initiating wound healing in insects as in vertebrates. It is also an important immune defense, quickly forming a secondary barrier to infection, immobilizing bacteria and thereby promoting their killing. However, hemolymph clotting is one of the least understood immune responses in insects. Here, we characterize fondue (fon; CG15825), an immune-responsive gene of Drosophila melanogaster that encodes an abundant hemolymph protein containing multiple repeat blocks. After knockdown of fon by RNAi, bead aggregation activity of larval hemolymph is strongly reduced, and wound closure is affected. Jon is thus the second Drosophila gene after hemolectin (hml), for which a knockdown causes a clotting phenotype. In contrast to hml-RNAi larvae, clot fibers are still observed in samples from fon-RNAi larvae. However, clot fibers from fon-RNAi larvae are more ductile and longer than in wt hemolymph samples, indicating that Fondue might be involved in cross-linking of fiber proteins. In addition, fon-RNAi larvae exhibit melanotic tumors and constitutive expression of the antifungal peptide gene Drosomycin (Drs), while fon-RNAi pupae display an aberrant pupal phenotype. Altogether, our studies indicate that Fondue is a major hemolymph protein required for efficient clotting in Drosophila.
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