Tolerance Induction in Experimental Autoimmune Encephalomyelitis Using Non-myeloablative Hematopoietic Gene Therapy With Autoantigen

Experimental autoimmune encephalomyelitis (EAE) constitutes a paradigm of antigen (Ag)-specific T cell driven autoimmune diseases. In this study, we transferred bone marrow cells (BMCs) expressing an autoantigen (autoAg), the peptide 40–55 of the myelin oligodendrocytic glycoprotein (MOG_40–55), to induce preventive and therapeutic immune tolerance in a murine EAE model. Transfer of BMC expressing MOG_40–55 (IiMOG-BMC) into partially myeloablated mice resulted in molecular chimerism and in robust protection from the experimental disease. In addition, in mice with established EAE, transfer of transduced BMC with or without partial myeloablation reduced the clinical and histopathological severity of the disease. In these experiments, improvement was observed even in the absence of engraftment of the transduced hematopoietic cells, probably rejected due to the previous immunization with the autoAg. Splenocytes from mice transplanted with IiMOG-BMC produced significantly higher amounts of interleukin (IL)-5 and IL-10 upon autoAg challenge than those of control animals, suggesting the participation of regulatory cells. Altogether, these results suggest that different tolerogenic mechanisms may be mediating the preventive and the therapeutic effects. In conclusion, this study demonstrates that a cell therapy using BMC expressing an autoAg can induce Ag-specific tolerance and ameliorate established EAE even in a nonmyeloablative setting.     

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??Abstract??Objective This study was designed to explore the changes in hydrogen sulfide??H2S?? and flow-mediated vasodilation??FMD?? in postural orthostatic tachycardia syndrome??POTS?? children and the relationship between them. Methods The study included 36 POTS children aged 11±3 and 18 normal children aged 11±4 as controls. The diagnosis of POTS was based on clinical manifestation and head-up test or head-up tilt test. The plasma concentration of H2S was determined by a sensitive sulphur electrode method and FMD of brachial artery was measured using color Doppler vascular ultrasound. Results There were no significant differences between the POTS and control groups in age?? sex ratio?? height?? weight?? body mass index and mean arterial pressure??P??0.05??. In POTS children?? the supine heart rate??88±15 bpm?? was higher than the controls??77±11 bpm??P=0.006 ??. Plasma H2S level was significantly higher in POTS group than in the control group??30.25±11.64 μmol/L in POTS group vs 17.58±1.74 μmol/L in control group??P??0.01??. The FMD in POTS group was significantly higher than in the controls??9.87±1.63% vs 5.92±2.14%??P??0.001??.In addition?? there was a significant positive correlations between H2S and FMD??r=0.565??P??0.001??.Conclusion Plasma H2S and FMD are significantly increased in POTS children. The abnormal vasodilation may play an important role in POTS of children.     

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??Helicobacter pylori??Hp?? infection rate is high and has strong pathogenicity??so the eradication of Hp has great significance. The combination of a proton pump inhibitor with two antibiotics??or bismuth-based triple therapy or quadruple therapy is recommended as a alternate first-line regimen for treating Hp infection in children. In recent years??the success of eradication therapies has declined??party due to the increassing rate of Hp resistant strains. Hp eradication therapy with probiotics has received more and more attention. In this article??we comprehensively review the possible mechanisms of probiotics in treating Hp infection in children??and its advantage in the prevention of antibiotic-associated side effects is also discussed.     

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??Sepsis is a major problem in the field of critical illness. One of the important reasons for the death of sepsis is the disorder of coagulation function??especially in the case of DIC. Coagulation dysfunction is always in the pathological process of sepsis??and its occurrence and prognosis is an important and independent prognostic factor. The activation of coagulation system and inflammatory response promote each other??and the inhibition of physiological anticoagulant system and fibrinolysis system are the pathophysiological basises of coagulation dysfunction in sepsis. Therefore??the anticoagulant therapy of sepsis has sufficient theoretical basis. However??there is no consistent conclusion about the treatment of sepsis at present. This article will discuss the mechanism of coagulation dysfunction and the research progress of anticoagulation therapy.     

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??Objective??To summarize the clinical characteristics and outcome of adolescent patients with acute lymphoblastic leukemia??ALL?? treated with Chinese Children’s Leukemia Group??CCLG??-2008 protocol over a 5-year period from 2008 to 2013. Methods??Clinical features??immunophenotypes??cytogenetic abnormalities and prognosis of adolescent patients aged 10 to 18 were compared with younger patients under 10 years old. Results??During 2008—2012??723 patients with ALL were enrolled in our study. About 14.11% of them were 10- to 18-year old patients. Compared to younger ones??adolescent patients demonstrated a higher incidence of T-cell lineage phenotype??14.71% vs 5.8%????t??9??22????8.82% vs. 4.99%????t??1??19????8.82% vs. 5.15%???? and significantly lower frequency of t??12??21????21.74% vs. 8.82%??. In intermediate group?? the 5-year overall survival rate??OS?? and event-free survival rate??EFS?? of adolescent patients was compatible with paediatric patients????92.88% vs. 90.86%?? and ??77.09% vs. 82.9%????respectively. However??the EFS of adolescent patients with high-risk ALL was worse than paediatric patients??42.78% vs. 54.12%??. Conclusion??Despite the increased incidence of adverse prognostic factors??the survival rate of adolescent patients has been improved when treated with paediatric ALL protocol. However??the poor prognosis of adolescent patients in the high-risk group remains to be the current challenge.     

Legionellosis Outbreak Associated with Asphalt Paving Machine, Spain, 2009

From 1999 through 2005 in Alcoi, Spain, incidence of legionellosis was continually high. Over the next 4 years, incidence was lower, but an increase in July 2009 led health authorities to declare an epidemic outbreak. A molecular epidemiology investigation showed that the allelic profiles for all Legionella pneumophila samples from the 2009 outbreak patients were the same, thus pointing to a common genetic origin for their infections, and that they were identical to that of the organism that had caused the previous outbreaks. Spatial-temporal and sequence-based typing analyses indicated a milling machine used in street asphalt repaving and its water tank as the most likely sources. As opposed to other machines used for street cleaning, the responsible milling machine used water from a natural spring. When the operation of this machine was prohibited and cleaning measures were adopted, infections ceased.