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91.
92.
Antigen/antibody complexes can efficiently target antigen presenting cells to allow stimulation of the cellular immune response. Due to the difficulty of manufacture and their inherent instability complexes have proved inefficient cancer vaccines. However, anti-idiotypic antibodies mimicking antigens have been shown to stimulate both antibody and T cell responses. The latter are due to T cell mimotopes expressed within the complementarity-determining regions (CDRs) of antibodies that are efficiently presented to dendritic cells in vivo. Based on this observation we have designed a DNA vaccine platform called ImmunoBody™, where cytotoxic T lymphocyte (CTL) and helper T cell epitopes replace CDR regions within the framework of a human IgG1 antibody. The ImmunoBody™ expression system has a number of design features which allow for rapid production of a wide range of vaccines. The CDR regions of the heavy and light chain have been engineered to contain unique restriction endonuclease sites, which can be easily opened, and oligonucleotides encoding the T cell epitopes inserted. The variable and constant regions of the ImmunoBody™ are also flanked by restriction sites, which permit easy exchange of other IgG subtypes. Here we show a range of T cell epitopes can be inserted into the ImmunoBody™ vector and upon immunization these T cell epitopes are efficiently processed and presented to stimulate high frequency helper and CTL responses capable of anti-tumor activity.Key words: DNA vaccines, cancer vaccines, melanoma, CTL, helper T cells 相似文献
93.
Olleros ML Guler R Corazza N Vesin D Eugster HP Marchal G Chavarot P Mueller C Garcia I 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(7):3394-3401
The contribution of a transmembrane (Tm) form of TNF to protective immunity against Mycobacterium bovis bacillus Calmette-Guérin (BCG) was studied in transgenic (tg) mice expressing a noncleavable Tm TNF but lacking the TNF/lymphotoxin-alpha (LT-alpha) locus (Tm TNF tg mice). These mice were as resistant to BCG infection as wild-type mice, whereas TNF/LT-alpha(-/-), TNF(-/-), and LT-alpha(-/-) mice succumbed. Tm TNF tg mice developed granulomas of smaller size but at 2- to 4-fold increased frequencies compared with wild-type mice. Granulomas were mainly formed by monocytes and activated macrophages expressing Tm TNF mRNA and accumulating acid phosphatase. NO synthase 2 activation as a key macrophage bactericidal mechanism was low during the acute phase of infection in Tm TNF tg mice but was still sufficient to limit bacterial growth and increased in late infection. While infection with virulent Mycobacterium tuberculosis resulted in very rapid death of TNF/LT-alpha(-/-) mice, it also resulted in survival of Tm TNF tg mice which presented an increase in the number of CFU in spleen (5-fold) and lungs (10-fold) as compared with bacterial load of wild-type mice. In conclusion, the Tm form of TNF induces an efficient cell-mediated immunity and total resistance against BCG even in the absence of LT-alpha and secreted TNF. However, Tm TNF-mediated protection against virulent M. tuberculosis infection can also be efficient but not as strong as in BCG infection, in which cognate cellular interactions may play a more predominant role in providing long-term surveillance and containment of BCG-infected macrophages. 相似文献
94.
Maras Powder (MP) is a special kind of smokeless tobacco widely used in the southeast region of Turkey especially in Kahramanmaras and Gaziantep and other southeastern cities. It is obtained from a tobacco species, Nicotiana rustica L and ash of oak or grapevine wood. Tobacco may increase oxidative stress, which is related to the products of the oxygen metabolism taking place in all cells. Cellular antioxidants, e.g. catalase (CAT), superoxide dismutase (SOD) and glucose 6-phosphate dehydrogenase (G6PD) protect the cell against oxidative damage. An imbalance between the ROS and antioxidants in favour of ROS is described as oxidative stress. In this study, we aimed to investigate the effect of MP on antioxidant enzyme levels and lipid peroxidation. We measured malondialdehyde (MDA), CAT, SOD and G6PD levels in blood of 68 MP users and 30 healthy controls who did not use MP. CAT, SOD and G6PD levels were lower in MP users than in the controls. On the other hand, lipid peroxidation levels (MDA), one of the best indicators of cytological damage, was increased in MP users compared with the controls. The present study showed that MP increases oxidative stress, which may cause many systemic disorders, including arteriosclerosis. 相似文献
95.
E?BaptesteEmail author E?Susko J?Leigh D?MacLeod RL?Charlebois WF?Doolittle 《BMC evolutionary biology》2005,5(1):33
Background
Since Darwin's Origin of Species, reconstructing the Tree of Life has been a goal of evolutionists, and tree-thinking has become a major concept of evolutionary biology. Practically, building the Tree of Life has proven to be tedious. Too few morphological characters are useful for conducting conclusive phylogenetic analyses at the highest taxonomic level. Consequently, molecular sequences (genes, proteins, and genomes) likely constitute the only useful characters for constructing a phylogeny of all life. For this reason, tree-makers expect a lot from gene comparisons. The simultaneous study of the largest number of molecular markers possible is sometimes considered to be one of the best solutions in reconstructing the genealogy of organisms. This conclusion is a direct consequence of tree-thinking: if gene inheritance conforms to a tree-like model of evolution, sampling more of these molecules will provide enough phylogenetic signal to build the Tree of Life. The selection of congruent markers is thus a fundamental step in simultaneous analysis of many genes. 相似文献96.
Oussaid B Lonergan P Khatir H Guler A Monniaux D Touze JL Beckers JF Cognie Y Mermillod P 《Journal of reproduction and fertility》2000,118(1):137-144
A GnRH antagonist (Antarelix) was used to suppress endogenous pulsatile secretion of LH and delay the preovulatory LH surge in superovulated heifers to study the effect of a prolonged follicular phase on both follicle and oocyte quality. Oestrous cycles were synchronized in 12 heifers with progestagen (norgestomet) implants for 10 days. On day 4 (day 0 = day of oestrus), heifers were stimulated with 24 mg pFSH for 4 days and luteolysis was induced at day 6 with PGF2 alpha (2 ml Estrumate). Animals in the control group (n = 4) were killed 24 h after the last FSH injection. At this time, heifers in group A36h (n = 4) and group A60h (n = 4) were treated with 1.6 mg of Antarelix every 12 h for 36 and 60 h, respectively, and then killed. After dissection of ovarian follicles, oocytes were collected for individual in vitro maturation, fertilization and culture; follicular fluid was collected for determination of steroid concentrations, and granulosa cells were smeared, fixed and stained for evaluation of pycnosis rates. Granulosa cell smears showed that 90% of follicles were healthy in the control group. In contrast, 36 and 58% of the follicles in group A36h showed signs of early or advanced atresia, respectively, while 90% of the follicles in group A60h showed signs of late atresia. Intrafollicular concentrations of oestradiol decreased (P < 0.0001) from healthy follicles (799.14 +/- 40.65 ng ml-1) to late atretic follicles (3.96 +/- 0.59 ng ml-1). Progesterone concentrations were higher (P < 0.0001) in healthy follicles compared with atretic follicles, irrespective of degree of atresia. Oestradiol:progesterone ratios decreased (P < 0.0001) from healthy (4.58 +/- 0.25) to late atretic follicles (0.07 +/- 0.009). The intrafollicular concentrations of oestradiol and progesterone were significantly higher (P < 0.0001) in the control than in the treated groups. The oestradiol:progesterone ratio was higher (P < 0.0001) in the control (4.55 +/- 0.25) than in the A36h (0.40 +/- 0.05) and A60h (0.07 +/- 0.009) groups. Unexpectedly, the cleavage rate of fertilized oocytes, blastocyst rate and number of cells per blastocyst were not significantly different among control (85%, 41% and 95 +/- 8), A36h (86%, 56% and 93 +/- 5) and A60h (88%, 58% and 79 +/- 4) groups. In addition, there were no significant differences in the blastocyst rates from oocytes derived from healthy (45%), early atretic (54%), advanced atretic (57%) and late atretic follicles (53%). In conclusion, the maintenance of the preovulatory follicles in superovulated heifers with a GnRH antagonist induced more atresia and a decrease in oestradiol and progesterone concentrations. However, the developmental potential in vitro to day 8 of the oocytes recovered from these atretic follicles was not affected. 相似文献
97.
Abiotic stresses occur together in several combinations in nature and do not usually act alone. However, studies on plants mainly are limited to a single stress type. Yet, atmospheric trends make it indispensable to expand approaches to investigate physiological consequences under multiple abiotic stresses. The potential of Melatonin (Mel) hydropriming on photosynthetic machinery and antioxidant system was investigated in this study. Mel hydropriming (0.1 mmol/mL) resulted in leaf photochemistry protection, which is characterized by maximum photochemical efficiency of PSII, photosynthetic pigments intactness, reactive oxygen species (ROS) scavenging enzymes activation accompanying depressed levels of endogenous hydrogen peroxide (H2O2) and membrane oxidation in maize seedlings at early vegetative stage under combination of 150 mM NaCl and 37?±?3 °C mild heat. Mimicking nature by combining stresses is more realistic to study abiotic stress responses. High antioxidant capacity of melatonin can serve as a hydropriming substance to withstand simultaneous heat and salt stress. 相似文献
98.
Walter RB; Rolig RL; Kozak KA; McEntire B; Morizot DC; Nairn RS 《Molecular biology and evolution》1993,10(6):1227-1238
Fishes represent the stem vertebrate condition and have maintained several
gene arrangements common to mammalian genomes throughout the 450 Myr of
divergence from a common ancestor. One such syntenic arrangement includes
the GPI-PEPD enzyme association on Xiphophorus linkage group IV and human
chromosome 19. Previously we assigned the Xiphophorus homologue of the
human ERCC2 gene to linkage group U5 in tight association with the CKM
locus. CKM is also tightly linked to the ERCC2 locus on human chromosome
19, leading to speculation that human chromosome 19 may have arisen by
fusion of two ancestral linkage groups which have been maintained in
fishes. To investigate this hypothesis further, we isolated and sequenced
Xiphophorus fish genomic regions exhibiting considerable sequence
similarity to the human DNA ligase 1 amino acid sequence. Comparison of the
fish DNA ligase sequence with those of other species suggests several modes
of amino acid conservation in this gene. A 2.2-kb restriction fragment
containing part of an X. maculatus DNA ligase 1 exon was used in backcross
hybrid mapping with 12 enzyme or RFLP loci. Significant linkage was
observed between the nucleoside phosphorylase (NP2) and the DNA ligase
(LIG1) loci on Xiphophorus linkage group VI. This assignment suggests that
the association of four DNA repair-related genes on human chromosome 19 may
be the result of chance chromosomal rearrangements.
相似文献
99.
100.
Electrophysiological and biochemical responses of mouse vomeronasal receptor cells to urine-derived compounds: possible mechanism of action 总被引:1,自引:1,他引:0
Receptor cells of the vomeronasal organ (VNO) are thought to detect
pheromone-like molecules important for reproductive physiology. Several
compounds derived from male mouse urine have been demonstrated to affect
endocrine events in female mice. In the present study, the ability of these
compounds to affect VNO activity was tested. In dissociated VNO cells held
under voltage clamp conditions, application of dehydro-exo-brevicomin (DHB)
evoked an outward current at negative holding potentials and an inward
current at positive holding potentials. Under current clamp, DHB reduced
action potential firing. Since DHB application caused a decrease in
membrane conductance, this compound appeared to act by reducing inward
current through closing an ion channel. Biochemical experiments tested the
effects of DHB and 2- (sec-butyl)-4,5-dihydrothiazole (SBT) on cAMP levels
in the VNO. A mixture of DHB and SBT decreased cAMP levels in VNO sensory
tissue and had no effect on VNO non-sensory tissue. The results suggest
that pheromones have an inhibitory influence on action potential generation
and on cAMP levels in receptor cells of the VNO.
相似文献