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61.
Defective expression of the apoptosis-inducing CD95 (Fas/APO-1) molecule on T and B cells in IDDM 总被引:2,自引:0,他引:2
C. Giordano R. De Maria G. Stassi M. Todaro P. Richiusa M. Giordano R. Testi A. Galluzzo 《Diabetologia》1995,38(12):1449-1454
Summary Triggering of CD95 (Fas/APO-1) cell surface receptors regulates the elimination of autoreactive T and B lymphocytes through a mechanism of cell suicide called apoptosis. Three different mutations involving CD95 or its ligand are responsible for induction of autoimmunity in susceptible mouse strains. To determine whether a defect involving the CD95 receptor is associated with human insulin-dependent diabetes mellitus (IDDM), we have studied the expression of CD95 on peripheral blood mononuclear cells from IDDM patients at different stages of the disease. Three-colour flow cytometry and mean fluorescence analysis showed that T and B lymphocytes from newly diagnosed IDDM and patients with long-standing disease, and subjects at high risk of developing the disease were highly defective in CD95 expression (p<0.001), whereas monocytes from all the groups studied expressed normal amounts of CD95 molecules on their cell surface. T-cell subset analysis showed that the impairment of CD95 expression in IDDM patients and high-risk subjects involved both CD3+ CD4+ (p<0.001) and CD3+ CD8+ cells (p range: <0.01–0.001), suggesting that this alteration concerns both helper and cytotoxic T cells. Moreover, after activation in vitro with anti-CD3 monoclonal antibody, T cells from newly diagnosed IDDM patients maintained a reduced CD95 expression during the entire cell culture period (24–72 h) in comparison to the control population (p<0.001). In conclusion, we found a reduced expression of the apoptosis-inducing CD95 receptor on T and B lymphocytes of individuals with clinical and preclinical IDDM. We hypothesize that this defective expression may impair the capacity of autoreactive lymphocytes to undergo CD95-mediated apoptosis, contributing to the lack of control on beta-cell specific B- and T-cell clones.Abbreviations MFI
Mean fluorescence intensity
- mAb
monoclonal antibody
- ICA
islet cell autoantibody
- IAA
insulin autoantibody
- PE
phycoerythrin
- FITC
fluorescein
- Per-CP
peridinid chlorophyll protein
- PBMC
peripheral blood mononuclear cells
- AICD
activation-induced cell death 相似文献
62.
Francesca Tatini Anna Maria Pugliese Chiara Traini Sandra Niccoli Giovanna Maraula Teresa Ed Dami Benedetta Mannini Tania Scartabelli Felicita Pedata Fiorella Casamenti Fabrizio Chiti 《Neurobiology of aging》2013
Protein misfolded oligomers are thought to be the primary pathogenic species in many protein deposition diseases. Oligomers by the amyloid-β peptide play a central role in Alzheimer's disease pathogenesis, being implicated in synaptic dysfunction. Here we show that the oligomers formed by a protein that has no link with human disease, namely the N-terminal domain of HypF from Escherichia coli (HypF-N), are also synaptotoxic. HypF-N oligomers were found to (i) colocalize with post-synaptic densities in primary rat hippocampal neurons; (ii) induce impairment of long-term potentiation in rat hippocampal slices; and (iii) impair spatial learning of rats in the Morris Water Maze test. By contrast, the native protein and control nontoxic oligomers had none of such effects. These results raise the importance of using HypF-N oligomers as a valid tool to investigate the pathogenesis of Alzheimer's disease, with advantages over other systems for their stability, reproducibility, and costs. The results also suggest that, in the context of a compromised protein homeostasis resulting from aggregation of the amyloid β peptide, a number of oligomeric species sharing common synaptotoxic activity can arise and cooperate in the pathogenesis of the disease. 相似文献
63.
目的:探讨儿童系统性红斑狼疮(systemic lupus erythematosus,SLE)外周血淋巴细胞表达CD95的特征及与疾病活动性和其他免疫学指标间的关系.方法:使用流式细胞术检测60例SLE患儿和20例对照外周血T淋巴细胞亚群和B淋巴细胞表面CD95的表达,并分析其与SLE疾病活动性以及实验室检查之间的关系.结果:初发SLE患儿外周血中CD4+T细胞表面CD95的表达显著高于对照组,差异有统计学意义(P<0.05);初发SLE患儿外周血中CD19+B细胞表面CD95的表达显著高于健康儿童(P<0.05);CD19+CD95+B细胞的比例和SLE疾病活动性呈正相关(r=0.4,P<0.05);CD4+CD95+T细胞的比例和SLE疾病活动性呈正相关(r=0.3,P<0.05),CD4+CD95+T细胞的比例和外周血抗双链DNA抗体(anti-dsDNA Abs)的水平呈正相关(r=0.2,P<0.05);治疗后SLE患儿外周血中CD19+CD95+B细胞和CD4+CD95+T细胞的比例均有显著下降,差异有统计学意义(P<0.05).结论:儿童SLE患者外周血中淋巴细胞表达CD95的水平显著升高,且与SLE的疾病活动性及血清中抗双链DNA抗体相关,可以作为SLE的评价指标. 相似文献
64.
Serological monitoring of protection of sheep against Echinococcus granulosus induced by the EG95 vaccine 总被引:1,自引:0,他引:1
Although immunity to Echinococcus granulosus in sheep has been shown to be antibody-mediated and complement-dependent and can be passively transferred in colostrum, in animals vaccinated with EG95, the relationship between protection against an oral challenge infection with E. granulosus eggs and anti-EG95 IgG ELISA absorbance values at the time of challenge has not been satisfactorily proven. Using a combination of results from three EG95 vaccination trials, we have found that the IgG ELISA absorbance at the time of challenge infection explains approximately 50% (P ≤ 0·001) of the variability in the percentage protection against an oral challenge with E. granulosus eggs (transformed with arcsin). 相似文献
65.
Christian Johana Baños-Hernández José Eduardo Navarro-Zarza Isela Parra-Rojas Mirna Vázquez-Villamar Jorge Ramón Padilla-Gutiérrez Yeminia Valle Zyanya Reyes-Castillo Nora Magdalena Torres-Carrillo Samuel García-Arellano Lorena Michele Brennan-Bourdon José Francisco Muñoz-Valle 《Human immunology》2017,78(9):553-558
Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_891G, PADI4_901T and PADI4_921G gene polymorphisms were associated with RA susceptibility (OR = 1.34, p = 0.04; OR = 1.35, p = 0.03; OR = 1.34, p = 0.04; respectively). The GTG haplotype was also significantly associated with RA (OR = 2.27 95%CI = 1.18–4.41; p = 0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA. 相似文献
66.
Fengjie Qi Yangyang Yuan Xuehong Zhi Qian Huang Yuexin Chen Wenxin Zhuang Dengcheng Zhang Bogang Teng Xiangyu Kong Yongxing Zhang 《International journal of clinical and experimental pathology》2015,8(2):1666-1673
Objective: To explore the expression of A-kinase anchor protein 95 (AKAP95), Cyclin D1, Cyclin E1, and Connexin43 (Cx43) in rectal cancer tissues and assess the associations between each of the proteins and pathological parameters, as well as their inter-relationships. Methods: AKAP95, Cyclin D1, Cyclin E1, and Cx43 protein expression rates were evaluated by immunohistochemistry in 50 rectal cancer specimens and 16 pericarcinoma tissues. Results: The positive rates of AKAP95, Cyclin E1, and Cyclin D1 proteins were 54.00 vs. 18.75%, 62.00 vs. 6.25%, and 72.00 vs. 31.25% in rectal cancer specimens and pericarcinoma tissues, respectively, representing statistically significant differences (P < 0.05). The positive rate of Cx43 protein expression in rectal cancer tissues was 44.00% and 62.50% in pericarcinoma tissues, and the difference between them was not significant (P > 0.05). No significant associations were found between protein expression of AKAP95, Cyclin E1, Cyclin D1, and Cx43, and the degree of differentiation, histological type, and lymph node metastasis of rectal cancer (P > 0.05). However, significant correlations were obtained between the expression rates of AKAP95 and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43 protein, and Cyclin D1 and Cx43, respectively (P < 0.05). Conclusion: AKAP95, Cyclin E1, and Cyclin D1 protein expression rates were significantly higher in rectal cancer tissues compared with pericarcinoma samples, suggesting an association between these proteins and the development and progression of rectal cancer. In addition, the significant correlations between the proteins (AKAP95 and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43 protein, and Cyclin D1 and Cx43) indicate the possible synergistic effects of these factors in the development and progression of rectal cancer. 相似文献
67.
《Vaccine》2015,33(24):2813-2822
BackgroundIn the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013–2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013–2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season.MethodsPractitioners systematically selected ILI patients to swab within eight days of symptom onset.We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I2 index and Cochrane's Q test. If the I2 was <50%, we estimated pooled VE as (1 minus the OR) × 100 using a one-stage model with study site as a fixed effect. If the I2 was >49% we used a two-stage random effects model.ResultsWe included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p = 0.695) and the I2 index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4–67.0).For A(H3N2), the I2 was 51.5% (p = 0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: −34.4–63.2).ConclusionsThe results suggest a moderate 2013–2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses. 相似文献
68.
Jessica M. Jarvis Karen Choong Mary A. Khetani 《Archives of physical medicine and rehabilitation》2019,100(4):703-710
Objective(s)
Determine the associations between having participation-focused strategies and receiving rehabilitation services in the pediatric intensive care unit (PICU) with caregiver stress over 6 months post-PICU discharge.Design
Substudy of a data from Wee-Cover, a prospective cohort study.Setting
Two PICU sites.Participants
Caregivers (N=168) of children 1-17 years old admitted into a PICU for ≥48 hours.Main Outcome Measures
Data were collected from caregivers at enrollment and 3 and 6 months post-PICU discharge. Caregiver stress was assessed using the Pediatric Inventory for Parents. Having strategies to support their child’s participation in home-based activities was assessed using the Participation and Environment Measure (PEM). In PEM, caregivers report on strategies used to support their child’s participation in home-based activities. Data were dichotomized (yes, no) to denote having participation-focused strategies and if their child received PICU rehabilitation services. Additional covariates were history of a preexisting condition, child age, length of PICU stay, and change in functional capacities at PICU discharge.Results
History of a preexisting condition, time, and change in functional capacities significantly predicted caregiver stress frequency and difficulty. The interaction of having strategies-by-rehabilitation-by-time significantly predicted caregiver stress frequency and difficulty.Conclusion(s)
Results highlight the role of early rehabilitation and the importance of working with caregivers to develop participation-focused strategies to support their child’s functioning post-PICU. Families of children with a preexisting condition or those who experience a decrease in function during a PICU stay are susceptible to higher levels of stress and may be a priority population to target for rehabilitation services. 相似文献69.
70.
Suzuki S Uozumi K Utsunomiya A Ishitsuka K Masamoto I Owatari S Makino T White Y Arima N 《European journal of haematology》2008,81(3):236-241
We describe a 44-yr-old Japanese woman with persistent polyclonal T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome (HPS). T cells bearing αβ T-cell receptors (TCR) expressed increased amounts of CD95 and of CD45RO, which are phenotypically memory T cells. The TCR repertoire was broad and diverse. Regardless of CD95 expression, these cells were resistant to CD95-mediated apoptosis. Aggressive natural killer cell leukaemia (ANKL) without an association with Epstein–Barr virus was detected 1 month after therapeutic splenectomy that followed 3 yr of immunosuppressive therapy against HPS. The immunophenotype of these leukaemia cells was CD56, CD16dim , CD7, CD45RA and they expressed some CD2, CD8 and HLA-DR. Moreover, hyperdiploid clones with complex chromosomal abnormalities were also detected. Latent NK-cell malignancy seemed to cause the CD95-resistant memory T-cell proliferation and splenectomy resulted in overt ANKL progression. There should be careful consideration of the risks versus benefits of splenectomy in HPS, in light of the possibility of fatal leukaemia/lymphoma progression. 相似文献