Viral epitope-specific T cell responses induced in chronic,hepatitis C virus-infected patients

BackgroundApproximate 180 million people worldwide are infected with hepatitis C virus (HCV). Historically, vaccination has been the most effective strategy for controlling infections of such major health concern. Therapeutic vaccine strategies for HCV, however, have demonstrated negligible success.AimDemonstrate the ability of highly-conserved viral epitopes to overcome the immune dysfunction often associated with chronic HCV infections.MethodsT cells from five chronic, HCV-infected patients were immunophenotyped by flow cytometry. The ex vivo T cell responses to highly-conserved viral epitopes were assessed by ELISpot assay and cytokine bead array analysis.ResultsBoth HLA-DRB-1- and HLA-A2-restricted viral epitopes induced specific, T_H1-type cytokine production by T cells derived from the patients. Induction occurred despite expression of cell-surface inhibitory molecules and the presence of regulatory T cells.ConclusionThese findings support the potential ability of a broad, multi-epitope-based therapeutic vaccine to elicit virus-specific immune responses in chronic hepatitis C virus-infected patients.     

重型β型地中海贫血患儿BNP和铁超负荷与早期心功能不全的关系研究

[目的]探讨重型β型地中海贫血患儿B型尿钠肽(BNP)和铁超负荷与早期心功能不全的关系.[方法]选择2014年1月至2016年1月本院收治的42例重型β型地中海贫血患儿为研究对象(观察组),选取同期40例健康儿童作为对照组,超声心动图检测心脏各参数,采集血标本检测血红蛋白、BNP和铁蛋白等指标.根据观察组是否合并舒张功能障碍分为E/E′(二尖瓣口舒张早期血流速度/室间隔舒张早期运动速度)<9和E/E′≥9两组,比较两组心脏各参数和血生化指标.[结果]观察组BNP和铁蛋白水平显著高于对照组,而血红蛋白低于对照组,差异均具有统计学意义(P<0.05);观察组左室舒张末期内径(LVED)、左室收缩末期内径(LVES)、左房直径(LV)、右室直径(RV)、左房容积指数(LAVI)和左室质量指数(LVMI)均高于对照组,差异均具有统计学意义(P<0.05);观察组E、二尖瓣口舒张晚期血流速度(A)、E/E′均高于对照组,等容舒张时间(IVRT)、室间隔收缩期运动速度(S′)、E′均低于对照组,其差异均具有统计学意义(P<0.05).E/E′≥9组E、E/E′、LVES、LVED、LA、LAVI和LVMI均高于E/E′<9组,E′低于于E/E′<9组,差异均具有统计学意义(P<0.05).观察组BNP水平与铁蛋白呈正相关(r=0.939,P=0.000),与血红蛋白无明显相关性(r=0.102,P=0.436);与S′和室间隔舒张晚期运动速度(A′)均呈负相关(r=-0.300、-0.421,P=0.043、0.031),与E/E′无相关性(r=0.082,P=0.519).E/E′<9组中,BNP水平与铁蛋白呈正相关(r=0.835,P=0.000),与E/A比值呈正相关(r=0.438,P=0.029).E/E′≥9组中,BNP水平与铁蛋白亦呈正相关(r=0.949,P=0.000),与LAVI呈正相关(r=0.396,P=0.026);BNP与S′和A′均呈负相关(r=-0.401、-0.409,P=0.035、0.036).[结论]重型β型地中海贫血儿童BNP水平与舒张功能障碍有关的参数无明显相关性,而与铁超负荷明显相关,可在一定程度上反映其心功能损害.     

心脏瓣膜置换术病人体外循环期间血浆内皮素、房钠利尿多肽和血流动力学变化

目的 了解体外循环（CPB）期间血浆内皮素（ET）、房钠利尿多肽（ANP）与血流动力学指标变化及其相互之间的关系。方法 用放射免疫法测定16例心脏瓣膜置换手术病人的术前及CPB期间血浆内皮素、房钠利尿多肽水平。结果 诱导前血浆ET为（2.68±1.8）pg/ml，与对照组[（2.22±0.7）pg/ml]相比无显著差异（P>0.05），而血浆ANP为（738±559）pg/ml，明显高于对照组[（72.7±14.5）pg/ml，P<0.001]。CPB期间血浆ET无明显变化，而血浆ANP在体外循环初期明显下降，停CPB时恢复至CPB前水平。CPB期间及停CPB时SVRI明显降低，血球压积（Hct）与血管阻力指数（SVRI）关系密切。结论 CPB期间血浆ET无明显变化，而血浆ANP下降为血液稀释所致，SVRI降低主要在于血液稀释。     

The distribution of Neuropeptide Y-immunoreactive neurons and nerve fibers in the forebrain of the carp Cyprinus carpio L.

The present study reports the distribution of Neuropeptide Y (NPY)-immunoreactive neurons and fibers in the forebrain of the adult carp Cyprinus carpio L.. Serial Nissl-stained sections were used for cytoarchitecture and identification of anatomical structures. Immunostaining of NPY-containing neurons and fibers was used as neurochemical marker and tool for comparison with other species, including the goldfish.The general outline of the cytoarchitecture of the carp forebrain is similar to that of other Cypriniformes. However, using NPY immunohistochemistry, we found several specific differences with the goldfish, especially in the diencephalon. In the hypothalamus of the carp NPY-immunoreactive (NPYir) neurons were identified in the n. dorsolateralis thalami, and in the n. ventralis lateralis thalami. In the same location, we observed the n. anterior hypothalami and the n. preglomerulosus pars lateralis, described in the goldfish, as parts of n. prerotundus. However, in the carp we were not able to identify a n. preglomerulosus pars medialis, a n. preglomerulosus pars medialis commissuralis and a n. glomerulosus. We describe a n. rotundus, in which we did not find substructures typical of the goldfish.Further differences with the goldfish, trout and salmon were also noted.     

Transport of prion protein across the blood-brain barrier

The cellular form of the prion protein (PrP^c) is necessary for the development of prion diseases and is a highly conserved protein that may play a role in neuroprotection. PrP^c is found in both blood and cerebrospinal fluid and is likely produced by both peripheral tissues and the central nervous system (CNS). Exchange of PrP^c between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications, but it is unknown whether PrP^c can cross the blood-brain barrier (BBB). Here, we found that radioactively labeled PrP^c crossed the BBB in both the brain-to-blood and blood-to-brain directions. PrP^c was enzymatically stable in blood and in brain, was cleared by liver and kidney, and was sequestered by spleen and the cervical lymph nodes. Circulating PrP^c entered all regions of the CNS, but uptake by the lumbar and cervical spinal cord, hypothalamus, thalamus, and striatum was particularly high. These results show that PrP^c has bidirectional, saturable transport across the BBB and selectively targets some CNS regions. Such transport may play a role in PrP^c function and prion replication.     

清醒大鼠内毒素休克时血浆CGRP浓度及血管对CGRP反应性的改变

清醒大鼠静脉注射内毒素16.7mg/Kg后在血压、心率、血浆葡萄糖、乳酸浓度和肠道损伤等方面表现出典型的内毒素休克改变。在注射内毒素后30分钟与180分钟时血浆中降钙素基因相关肽(CGRP)的浓度显著增高,而腹主动脉对CGRP的反应性没有改变。血浆CGRP浓度的增高可能对内毒素休克的发生发展过程具有重要影响。     

对梭状芽孢厌氧菌有作用的新抗生素T0007A的研究——Ⅱ.抗生素T0007A的分离和鉴别

从一株吸水链霉菌的培养液中分离得到对难辨梭状芽孢杆菌有作用的抗生素T0007A。基于其理化及生物学性质、光谱特征和氨基酸分析结果,确认抗生素T0007A为由脯氨酸∶亮氨酸∶异亮氨酸(8∶7∶1)组成的新肽类抗生素。     

Contransmitters: differential effects of serotonin (5-HT)-depleting drugs on levels of 5-HT and TRH and their receptors in rat brain and spinal cord

Following codepletion of endogenous serotonin (5-HT, >90%) and thyrotropin-releasing hormone (TRH, 66%) by neonatal treatment with the serotonergic neurotoxin, 5,7-dihydroxytryptamine (DHT), a 33% (n = 12, P < 0.01) increase in specific TRH receptor binding was observed in adult rat spinal cord (SC) homogenates. A 20–21% increase in TRH receptors was also observed in the medulla/pons (MP) (n = 12, P < 0.05) and midbrain (MB) (n = 12, P < 0.02), but no changes were detected in 6 rostral brain regions. The depletion of 5-HT after DHT-treatment was also accompanied by a 34–42% increase in 5-HT₁ binding in the SC, MP and MB. Eadle-Hofstee analysis revealed that the changes in TRH receptor levels observed after DHT-lesions were due to an increase in receptor number rather than any significant changes in receptor affinity. Chronic treatment of adult rats with the 5-HT-depleting drugs, p-chlorophenylalanine (PCPA) and reserpine, produced a 90–97% decrease in 5-HT in the SC, MP and MB and elevated 5-HT₁ binding in any of these tissues. In conclusion, these results have provided further support for the coexistence of 5-HT and TRH in the MP and SC and revealed possible new areas of such colocalization in the MB. Furthermore, these data have demonstrated that only DHT-treatment, as apposed to PCPA or reserpine, can produce long-lasting codepletion of 5-HT and TRH with simultaneous compensatory up-regulation of their receptor systems in the SC and other caudal tissues.     

Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.