Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo

Increasing evidence suggests that antibodies can have stimulatory effects on T‐cell immunity. However, the contribution of circulating antigen‐specific antibodies on MHC class I cross‐priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross‐presentation of antigen to CD8⁺ T cells. Mice with hapten‐specific circulating antibodies, but na?ve for the T‐cell antigen, were infused with haptenated antigen and CD8⁺ T‐cell induction was measured. Mice with circulating hapten‐specific antibodies showed significantly enhanced cross‐presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross‐presentation in mice with circulating antigen‐specific antibodies was associated with improved antigen capture by APCs. Importantly, CD11c⁺ APCs were responsible for the enhanced and sustained cross‐presentation, although CD11c^? APCs had initially captured a significant amount of the injected antigen. Thus, in vivo formation of antigen‐antibody immune complexes improves MHC class I cross‐presentation, and CD8⁺ T‐cell activation, demonstrating that humoral immunity can aid the initiation of systemic cellular immunity. These findings have important implications for the understanding of the action of therapeutic antibodies against tumor‐associated antigens intensively used in the clinic nowadays.     

Design of neo-glycoconjugates that target the mannose receptor and enhance TLR-independent cross-presentation and Th1 polarization

Cross-presentation is an important mechanism by which DCs present exogenous antigens on MHC-I molecules, and activate CD8(+) T cells, cells that are crucial for the elimination of tumors. We investigated the feasibility of exploiting the capacity of the mannose receptor (MR) to improve both cross-presentation of tumor antigens and Th polarization, processes that are pivotal for the anti-tumor potency of cytotoxic T cells. To this end, we selected two glycan ligands of the MR, 3-sulfo-Lewis(A) and tri-GlcNAc (N-acetylglucosamine), to conjugate to the model antigen OVA and assessed in vitro the effect on antigen presentation and Th differentiation. Our results demonstrate that conjugation of either 3-sulfo-Lewis(A) or tri-GlcNAc specifically directs antigen to the MR. Both neo-glycoconjugates showed, even at low doses, improved uptake as compared with native OVA, resulting in enhanced cross-presentation. Using MR(-/-) and MyD88-TRIFF(-/-) bone marrow-derived DCs (BMDCs), we show that the cross-presentation of the neo-glycoconjugates is dependent on MR and independent of TLR-mediated signaling. Whereas proliferation of antigen-specific CD4(+) T cells was unchanged, stimulation with neo-glycoconjugate-loaded DCs enhanced the generation of IFN-γ-producing T cells. We conclude that modification of antigen with either 3-sulfo-Lewis(A) or tri-GlcNAc enhances cross-presentation and permits Th1 skewing, through specific targeting of the MR, which may be beneficial for DC-based vaccination strategies to treat cancer.     

Women's use of complementary and alternative medicines during pregnancy: A cross-sectional study

Objective

to determine the prevalence of women's use of complementary and alternative medicines (CAM) during pregnancy in the UK, reasons for use, who recommended CAM, and the characteristics of women that are associated with use of CAM during pregnancy.

Design

cross-sectional questionnaire.

Setting

Birmingham Women's Hospital.

Participants

315 postnatal women were surveyed while on the postnatal ward.

Findings

the questionnaire response rate was 89% (315/355). CAM use during pregnancy was reported by 180 women (57.1%). CAM users differed significantly from non-CAM users by education level, parity and previous CAM use before pregnancy. Vitamins (34.9%), massage therapy (14.0%), yoga (11.1%) and relaxation (10.2%) were the most commonly reported uses of CAM. 33.0% of women reported they did not disclose their use of CAM to a doctor or midwife, and 81.3% were not asked by their doctor or midwife about their use of CAM during pregnancy.

Key conclusions and implications for practice

this study found a high prevalence of CAM use during pregnancy, which is within the range of findings of studies from Australia and Germany. It is important that health-care providers routinely ask about CAM use during pregnancy and are able to provide pregnant women with appropriate advice regarding CAM use.     

人工软骨材料——聚乙烯醇水凝胶的研制

聚乙烯醇溶液于－２０℃左右的温度下冷冻６－１２ｈ,室温下颌化１－２ｈ,上述过程反复进行１－３次,然后对试样进行真空脱水处理,制得一种人工软骨材料－ＰＶＡ水凝胶。     

Diagnosis of Parasitic Zoonoses by Immunoenzymatic Assays—Analysis of Cross‐Reactivity Among the Excretory/Secretory Antigens of Fasciola hepatica,Toxocara canis,and Ascaris suum

Several parasitic infections such fasciolosis, toxocariosis or ascariosis are important zoonoses. During the infection with Fasciola hepatica, Toxocara canis and Ascaris suum, an important intraorganic phase in their hosts takes place, releasing antigens responsible for a humoral immune response, which enables the diagnosis of that parasitosis. A study to identify the existence of cross‐reactivity among the excretory/secretory antigens of F. hepatica, T. canis and A. suum was developed. One group of Sprague–Dawley rats was infected with 20 metacercariae of F. hepatica and another group remained uninfected as control. By means of an Indirect‐ELISA, the rat humoral immune response (IgG and IgM) against the excretory/secretory antigens of F. hepatica was analysed and measured for cross reactivity with T. canis and A. suum. IgM cross‐reaction was mainly observed in the first 10 weeks post‐infection. IgG cross‐reaction was observed throughout the study, and was maximal at the 2–3 weeks and 3–6 weeks post‐infection, which corresponds to the intraorganic migratory phase of these parasites. The western‐blot showed that the rat IgG recognised three proteins of 190, 160 and 33 kDa in the antigens from F. hepatica, T. canis and A. suum. The existence of cross‐reactivity among these antigens seems to demonstrate also the presence of structural similarities, such as tegumental proteins. These results should be consider when immunoassay probes are used in the diagnosis of parasitic infections.     

Novel spontaneous myelodysplastic syndrome mouse model

BackgroundMyelodysplastic syndrome (MDS) is a group of disorders involving hemopoietic dysfunction leading to leukemia. Although recently progress has been made in identifying underlying genetic mutations, many questions still remain. Animal models of MDS have been produced by introduction of specific mutations. However, there is no spontaneous mouse model of MDS, and an animal model to simulate natural MDS pathogenesis is urgently needed.MethodsIn characterizing the genetically diverse mouse strains of the Collaborative Cross (CC) we observed that one, designated JUN, had abnormal hematological traits. This strain was thus further analyzed for phenotypic and pathological identification, comparing the changes in each cell population in peripheral blood and in bone marrow.ResultsIn a specific‐pathogen free environment, mice of the JUN strain are relatively thin, with healthy appearance. However, in a conventional environment, they become lethargic, develop wrinkled yellow hair, have loose and light stools, and are prone to infections. We found that the mice were cytopenic, which was due to abnormal differentiation of multipotent bone marrow progenitor cells. These are common characteristics of MDS.ConclusionsA mouse strain, JUN, was found displaying spontaneous myelodysplastic syndrome. This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models. JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.     

Crossed doubled patellar tendon: A rare anatomical variant with potential clinical significance

The patellar tendon is an integral part of the knee extensor mechanism and has been historically described as a single tendon. A doubled patellar tendon is an exceedingly rare finding. We present a case of a crossed doubled patellar tendon in a 70-year-old male with a history of right knee pain, which to our knowledge has only been reported once before in the literature. The presence of a doubled patellar tendon has a potential influence on surgical planning and in the etiology of anterior knee pain.     

四型念珠菌与抗念珠菌血清的交叉免疫反应

目的 分析4型不同念珠菌抗血清的免疫应答状况,为念珠菌疫苗的研制奠定实验基础.方法 将白色念珠菌、热带念珠菌、吉利蒙念珠菌、假热带念珠菌4型念珠菌分别超声破碎,0.5％甲醛溶液灭活,加入弗氏完全佐剂制成灭活全菌疫苗.分别在1、4、8、12周腹腔注射免疫小鼠,4周后收集小鼠抗体血清,分别按10、100、1000倍稀释,再分别加入含200μl4种念珠菌的沙氏培养液中,观察其抑菌作用.结果 所有抗体均为10倍效果最佳,1000倍基本无效.白色念珠菌抗体血清对白色念珠菌、吉利蒙念珠菌、热带念珠菌有明显的抑菌作用（P＜0.01）;热带念珠菌抗体血清对白色念珠菌和热带念珠菌有抑菌作用（P=0.01）;吉利蒙念珠菌抗体血清对吉利蒙念珠菌、热带念珠菌有抑制作用（P＜0.01）;假热带念珠菌抗体血清对热带念珠菌、假热带念珠菌有抑制作用（P＜0.01）.结论 小鼠念珠菌免疫抗体血清对念珠菌的生长有一定的抑制作用.     

Dental caries prevalence and treatment needs of 5- to 12-year-old children in relation to area-based income and immigrant background in Greece

Objectives: To investigate the association between certain socio‐demographic characteristics and dental health status of 5‐ to 12‐year‐old children attending public kindergarten and primary schools in Piraeus, Greece. Methods: Gender, age, place of residence, immigrant background and area‐based income were associated with dental caries prevalence, treatment needs and oral hygiene level in 5,116 children. Results: The mean number of decayed, missing and filled deciduous teeth (dmft) and Unmet Restorative Treatment Needs Index (UTN) at 6‐year‐olds were 1.54 and 84.6% respectively, and the DMFT and UTN at 12‐year‐olds were 1.35 and 71.8%. Caries experience/severity significantly increased with age, whereas treatment needs and oral hygiene level decreased (P < 0.001). Immigrant background and low area‐based income was associated with poorer oral health outcomes. The above associations retained statistical significance after multivariate analysis. Children who live in areas with lower average income present 1.20 to 2.14 greater risk of having higher caries severity and poorer oral hygiene in comparison to those living in more affluent areas, and children with an immigrant background have 1.68 to 4.34 higher likelihood to present higher dmft and DMFT values, higher unmet treatment needs, and poorer oral hygiene levels compared to their Greek counterparts above and beyond the effect of the other risk factors assessed. Conclusions: The present study revealed a socio‐demographic gradient in oral health status and treatment needs of children in Piraeus, Greece.