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51.
BACKGROUND: Human immunodeficiency virus 1 (HIV-1)-infected individuals are commonly infected with herpesviruses, including cytomegalovirus, herpes simplex virus, varicella-zoster virus, and human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus [KSHV]). Previous studies have demonstrated that coinfection with herpesviruses can modulate HIV-1 replication. This can occur either through direct interaction between the 2 viruses or through secondary effects resulting from the release of cellular factors in response to infection. OBJECTIVE: To investigate HIV-1 replication in the presence and absence of HHV-8. DESIGN AND METHODS: HIV-1 replication was analyzed following culture of HIV-1-infected CD4(+) T cells in the presence of HHV-8 infected B-cell lines or control, uninfected B-cell lines. To confirm and extend the results of these in vitro studies, HIV-1-infected T cells were injected into human skin transplanted onto severe combined immunodeficient mice. The human skin was also injected with purified HHV-8 or phosphate-buffered saline as a control and HIV replication measured in biopsy specimens taken 5 to 8 days later. RESULTS AND CONCLUSIONS: The results demonstrated a significant increase in HIV-1 replication in the presence of HHV-8 in both the in vitro and in vivo model systems. Although the mechanism responsible for HHV-8 induction of HIV-1 replication remains to be identified, the results indicate that these 2 viruses may interact at the molecular level in coinfected patients, resulting in increased HIV-1 viral load. 相似文献
52.
Winn LM Kim PM Nickoloff JA 《The Journal of pharmacology and experimental therapeutics》2003,306(2):523-527
Although the mechanism(s) of phenytoin-initiated toxicity is unknown, phenytoin can be enzymatically bioactivated to a reactive intermediate leading to increased formation of reactive oxygen species, which can damage essential macromolecules, including DNA. The oxidation of DNA can induce DNA double-strand breaks (DSBs), which may be repaired through homologous recombination. Increased levels of DSBs may induce hyper-recombination, leading to deleterious genetic changes. We hypothesize that these genetic changes mediate phenytoin-initiated toxicity. To investigate this hypothesis we used a Chinese hamster ovary cell line containing a neo direct repeat recombination substrate to determine whether phenytoin-initiated DNA oxidation increases homologous recombination. Cells were treated with 0 to 800 microM phenytoin for 5 or 24 h, and homologous recombination frequencies and recombinant product structures were determined. Phenytoin-initiated DNA oxidation was determined by measuring the formation of 8-hydroxy-2'-deoxyguanosine. We demonstrate that phenytoin increases both DNA oxidation and homologous recombination in a concentration- and time-dependent manner. All recombination products analyzed arose via gene conversion without associated crossover. Our data demonstrate that phenytoin-initiated DNA damage can induce homologous recombination, which may be a novel mechanism mediating phenytoin-initiated toxicity. 相似文献
53.
T cell-dependent antitumor immunity mediated by secondary lymphoid tissue chemokine: augmentation of dendritic cell-based immunotherapy 总被引:28,自引:0,他引:28
Kirk CJ Hartigan-O'Connor D Nickoloff BJ Chamberlain JS Giedlin M Aukerman L Mule JJ 《Cancer research》2001,61(5):2062-2070
Secondary lymphoid tissue chemokine (SLC) is a CC chemokine that is selective in its recruitment of naive T cells and dendritic cells (DCs). In the lymph node, SLC is believed to play an important role in the initiation of an immune response by colocalizing naive T cells with DC-presenting antigen. Here, we used SLC as a treatment for tumors established from the poorly immunogenic B16 melanoma. Intratumoral injections of SLC inhibited tumor growth in a CD8+, T cell-dependent manner. SLC elicited a substantial infiltration of DCs and T cells into the tumor, coincident with the antitumor response. We next used SLC gene-modified DCs as a treatment of established tumors. Intratumoral injections of SLC-expressing DCs resulted in tumor growth inhibition that was significantly better than either control DCs or SLC alone. Distal site immunization of tumor-bearing mice with SLC gene-modified DCs pulsed with tumor lysate elicited an antitumor response whereas control DCs did not. We also found that s.c. injection of lysate-pulsed DCs expressing SLC promoted the migration of T cells to the immunization site. This report demonstrates that SLC can both induce antitumor responses and enhance the antitumor immunity elicited by DCs. 相似文献
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目的:严重的黏膜损伤是诱发造血干细胞移植后出现并发症的一常见原因,已有证据显示谷氨酰胺能降低接受化疗患儿黏膜炎的发生率。观察谷氨酰胺对异基因外周造血干细胞移植患者并发症及恢复的影响。方法:选择于2002-03/2006-11在河南省血液病研究所接受同胞异基因外周造血干细胞移植的48例血液系统肿瘤患者。所有患者及其家属对治疗和实验均知情同意,并经医院伦理委员会批准。所有患者移植前均处于完全缓解状态,营养中等或良好,心、肝、肾功能正常,将48例患者随机分为标准化全胃肠外营养液组(标准组,n=13)和加用谷氨酰胺的全胃肠外营养液组(谷氨酰胺组,n=35)。待患者中性粒细胞升至1.0×109L-1,且无任何感染指征,进行异基因外周造血干细胞移植。造血干细胞输注后第1天开始给予全胃肠外营养与胃肠外营养联合谷氨酰胺双肽,至中性粒细胞≥1.0×109L-1,且无消化道症状时停用。观察两组患者中性粒细胞恢复时间、出层流室时间以及关于感染、急性移植物抗宿主病等情况有无差异。结果:48例患者均进入结果分析。两组患者营养物质的摄入基本相同,谷氨酰胺组有6例发生黏膜炎,标准组有11例,差异显著(P<0.05);谷氨酰胺组有1例发生严重腹泻,标准组有5例,差异显著(P<0.05);谷氨酰胺组有3例发生临床感染,标准组有7例,差异显著(P<0.05);标准组中性粒细胞≥0.5×109L-1的持续时间短于谷氨酰胺组(P>0.05);谷氨酰胺组抗生素治疗时间及无菌病房居住时间较标准组短(P<0.05);两组急性移植物抗宿主病发生率差异无统计学意义(P>0.05)。结论:添加谷氨酰胺的全胃肠外营养可改善异基因造血干细胞移植患者的营养状态,减少感染及肠损害,减少急性移植物抗宿主病的发生,有利于异基因移植患者恢复。 相似文献
56.
J Varani B J Nickoloff B L Riser R S Mitra K O''''Rourke V M Dixit 《The Journal of clinical investigation》1988,81(5):1537-1544
Human epidermal keratinocytes obtained from normal skin attached and spread on thrombospondin (TSP)-coated plastic dishes but failed to attach and spread on untreated plastic culture dishes or dishes coated with fibronectin or laminin. These cells produced minimal amounts of immunoreactive TSP. Keratinocytes established in culture on MCDB 153 medium and maintained for one to three passages in an undifferentiated state by continued cultivation in this low Ca2+-containing medium attached and spread on plastic dishes as well as on TSP-coated dishes. These cells also secreted significant amounts of TSP into the culture medium. When the keratinocytes were incubated for one day in MCDB 153 medium supplemented with high Ca2+ or in MEM (which also contains high Ca2+), there was decreased secretion of TSP into the culture medium concomitant with a reduction in attachment and spreading on plastic culture dishes. Proteolytic fragments of TSP were examined for stimulation of keratinocyte attachment and spreading. A 140-kd fragment produced by removal of the 25-kd heparin-binding domain had similar activity to the intact molecule while the 25-kd fragment was without effect. Further proteolytic treatment of the 140-kd fragment gave rise to a fragment consisting of 120 kd and 18-D moieties held together in disulphide linkage. This fragment did not support attachment or spreading. This study reveals that normal epidermal keratinocytes grown under conditions that maintain the undifferentiated state are able to produce TSP and utilize it as an attachment factor. When keratinocytes are grown under conditions that promote differentiation, ability to produce and utilize TSP is diminished. Since TSP is present at the dermal-epidermal junction and because TSP promotes keratinocyte attachment and spreading, this molecule may play an important role in maintaining normal growth of the basal cell layer and may also participate in reepithelialization during wound repair. 相似文献
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Braffman BH; Coleman BG; Ramchandani P; Arger PH; Nodine CF; Dinsmore BJ; Louie A; Betsch SE 《Radiology》1994,190(3):797