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排序方式: 共有223条查询结果,搜索用时 15 毫秒
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Haigwood NL Pierce CC Robertson MN Watson AJ Montefiori DC Rabin M Lynch JB Kuller L Thompson J Morton WR Benveniste RE Hu SL Greenberg P Mossman SP 《Immunology letters》1999,66(1-3):183-188
To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone and in combination with subunit protein boosts. All of the structural and regulatory genes of SIVmne clone 8 were cloned into mammalian expression vectors under the control of the CMV IE-1 promoter. Eight M. fascicularis were immunized twice with 3 mg of plasmid DNA divided between two sites; intramuscular and intradermal. Four primed macaques received a further two DNA immunizations at weeks 16-36, while the second group of four were boosted with 250 microg recombinant gp160 plus 250 microg recombinant Gag-Pol particles formulated in MF-59 adjuvant. Half of the controls received four immunizations of vector DNA; half received two vector DNA and two adjuvant immunizations. As expected, humoral immune responses were stronger in the macaques receiving subunit boosts, but responses were sustained in both groups. Significant neutralizing antibody titers to SIVmne were detected in one of the subunit-boosted animals and in none of the DNA-only animals prior to challenge. T-cell proliferative responses to gp160 and to Gag were detected in all immunized animals after three immunizations, and these responses increased after four immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of challenge showed trends toward Thl responses in 2/4 macaques in the DNA vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2 responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4 controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell clones (CD3+ CD8+) were isolated after only two DNA immunizations, and Gag-Pol- and Nef-specific CTL lines were isolated on the day of challenge. All animals were challenged at week 38 with SIVmne uncloned stock by the intrarectal route. Based on antibody anamnestic responses (western, ELISA, and neutralizing antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences between the groups in the challenge outcome. Surprisingly, sustained low virus loads were observed only in the DNA group, suggesting that four immunizations with DNA only elicited more effective immune responses than two DNA primes combined with two protein boosts. Multigenic DNA vaccines such as these, bearing all structural and regulatory genes, show significant promise and may be a safe alternative to live-attenuated vaccines. 相似文献
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The presence of checkpoint mechanisms which are able to recognize damaged
chromatin and thereafter to prevent exit from metaphase I has been
investigated in giant mouse oocytes produced by fusion of a normal
metaphase I oocyte with an equivalent oocyte with damaged chromatin. The
presence of damaged chromatin did not prevent the onset of anaphase I in
both sets of chromatin in the fused cells. Interestingly, fused or unfused
cells containing only damaged chromatin failed to enter anaphase and
persisted instead in a metaphase-like state. These results demonstrate the
fragility of checkpoint controls in mammalian female germ cells.
相似文献
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Thrombopoietin (Tpo), the ligand for the c-Mpl receptor, is a major regulator of megakaryopoiesis. Treatment of mice with Tpo raises the platelet count fourfold within a few days. Conversely, c-mpl knock-out mice have platelet counts that are 15% that of normal. The subunit structure of the c-Mpl receptor is not fully understood. Some cytokines that stimulate megakaryopoiesis (IL-6, IL-11, leukemia inhibitory factor, and oncostatin M) bind to receptors that use gp130 as a signal transduction subunit. For these reasons, we determined whether gp130 function was required for Tpo-induced signal transduction. Murine marrow cells were cultured in semi-solid media in the presence of Tpo or IL-3, with or without a neutralizing anti-gp130 monoclonal antibody (RX187) or a soluble form of c-Mpl receptor (soluble Mpl) that blocks Tpo bioactivity, and the numbers of colony-forming unit-megakaryocyte (CFU-Meg) colonies were counted on day 5. Murine marrow cells were also cultured in suspension under serum-free conditions for 5 days, and megakaryocyte DNA content was measured by flow cytometry, as an index of nuclear maturation. The addition of RX187 did not block Tpo-induced CFU-Meg colony growth nor CFU-Meg nuclear maturation in suspension culture. However, IL-3-induced CFU-Meg colony growth and megakaryocyte nuclear maturation decreased in the presence of RX187. Soluble Mpl completely ablated Tpo-induced CFU-Meg growth, and partially blocked IL- 3-stimulated CFU-Meg growth. Thus the effects of Tpo on megakaryopoiesis in vitro do not depend on cytokines that signal through gp130. Furthermore, it is unlikely that gp 130 serves as a beta chain for the c-Mpl receptor, as Tpo signalling is unimpaired in the presence of RX187. In contrast, the effects of IL-3 on CFU-Meg growth are mediated in part through Tpo and through gp130-signalling cytokines. 相似文献
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NL Vasukutty RG Middleton P Young C Uzoigwe B Barkham S Yusoff THA Minhas 《Annals of the Royal College of Surgeons of England》2014,96(8):597-601
IntroductionDislocation following total hip replacement continues to be a problem for which no completely satisfactory solution has been found. Several methods have been proposed to reduce the incidence of hip dislocations with varying degrees of success, including elevated rim liners, constrained liners and large diameter bearings. We present our experience with the double mobility acetabular component in patients at high risk of instability.MethodsThis was a retrospective review of 65 primary total hip arthroplasties in 55 patients (15 men, 40 women), performed between October 2005 and November 2009. The majority (80%) of patients had at least two and 26% had at least three risk factors for instability. The mean age was 76 years (range: 44–92 years). The patients were followed up for a mean duration of 60 months (range: 36–85 months).ResultsFourteen patients died and one was lost to follow-up, leaving fifty hips for final assessment. Until the final follow-up appointment, no patients had dislocation and none required revision surgery. The mean Oxford hip score improved from 45.0 to 26.5 (p<0.0001). The mean Merle d’Aubigné pain score improved from 1.4 to 4.9 (p<0.0001), the walking score from 2.3 to 3.1 (p<0.07) and the absolute hip function score from 5.4 to 10.8 (p<0.0001). There were no clinical or radiographic signs of loosening.ConclusionsThe double mobility acetabular component was successful at preventing dislocation during early to medium-term follow-up. However, as data are still lacking with regard to polyethylene wear rates at the additional bearing surface, it would be prudent to restrict the use of this implant to selected patients at high risk of instability. 相似文献
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Priming of CD4+ T cells specific for conserved regions of human immunodeficiency virus glycoprotein gp120 in humans immunized with a recombinant envelope protein.
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S Abrignani D Montagna M Jeannet J Wintsch N L Haigwood J R Shuster K S Steimer A Cruchaud T Staehelin 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(16):6136-6140
A nonglycosylated denatured form of human immunodeficiency virus (HIV) 1 glycoprotein gp120 (Env 2-3), which does not bind to CD4, was used with muramyl tripeptide as adjuvant to immunize HIV-seronegative healthy volunteers. In all the volunteers, three 50-micrograms injections of Env 2-3 induced priming of CD4+ T cells specific for conserved regions of the native glycosylated gp120. Moreover, we found that several major histocompatibility complex class II (DR) alleles can function as restriction molecules for presentation of conserved epitopes of gp120 to T cells, implying that a T-cell response to these epitopes can be obtained in a large fraction of the population. The possibility to prime CD4+ T cells specific for conserved epitopes of a HIV protein is particularly important in view of the lack of such cells in HIV-infected individuals and of a possible role that CD4+ T cells may play in the development of protective immunity against AIDS. 相似文献
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Evaluation of atypical human immunodeficiency virus immunoblot reactivity in blood donors 总被引:6,自引:0,他引:6
NL Dock ; HV Lamberson Jr ; TA O''Brien ; DE Tribe ; SS Alexander ; BJ Poiesz 《Transfusion》1988,28(5):412-418
Blood donors reactive by enzyme-linked immunosorbent assay for antibody to the human immunodeficiency virus (HIV) who showed atypical patterns of viral core protein reactivity on Western blot were monitored for several months. Characterization of their antibodies was performed by 1) use of recombinant HIV proteins; 2) determination of cross-reactivity to HTLV-I, HTLV-II, and HTLV-IV: 3) assessment of immune status; and 4) identification of potentially interfering autoantibodies. Nineteen of 20 donors maintained the same HIV antibody reactivity throughout the follow-up period; the other donor became fully antibody-positive. Eighteen of 20 donors' sera showed clear reactivity with HIV recombinant core proteins. Ten of 19 donor samples demonstrated cross-reactivity to HTLV-IV; 3 of these 10 also cross-reacted with HTLV-I. The immune status of all donors was normal, although the medical histories and HLA antibody screens suggested possible autoimmune reactivity in 9 of 18 donors. During follow-up interviews, three donors reported possible risk factors for HIV infection that had not been acknowledged at the time of blood donation. We conclude that exclusion of donors with these atypical serologic test results is warranted while further studies to determine significance are being conducted. 相似文献
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