Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas(lpr) mice from autoimmune disease

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LFA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas(lpr) mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(lpr) mice, suggesting a lack of redundancy among the beta(2) integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE.     

A PKC epsilon-ENH-channel complex specifically modulates N-type Ca2+ channels

Multiple protein kinase C (PKC) isozymes are present in neurons, where they regulate a variety of cellular functions. Due to the lack of specific PKC isozyme inhibitors, it remains unknown how PKC acts on its selective target(s) and achieves its specific actions. Here we show that a PKC binding protein, enigma homolog (ENH), interacts specifically with both PKCepsilon and N-type Ca2+ channels, forming a PKCepsilon-ENH-Ca2+ channel macromolecular complex. Coexpression of ENH facilitated modulation of N-type Ca2+ channel activity by PKC. Disruption of the complex reduced the potentiation of the channel activity by PKC in neurons. Thus, ENH, by interacting specifically with both PKCepsilon and the N-type Ca2+ channel, targets a specific PKC to its substrate to form a functional signaling complex, which is the molecular mechanism for the specificity and efficiency of PKC signaling.     

Ⅱ型糖尿病模型db／db小鼠胰岛α细胞超微结构变化

目的:观察Ⅱ型糖尿病模型 db/db 小鼠胰岛α细胞的超微结构变化,探讨α细胞的病理改变与Ⅱ型糖尿病病因的关系.方法:选取 3、5、8 月龄尾静脉空腹血糖高于10.1 mmol/L,且肥胖的 db/db 自发性精尿病小鼠作为糖尿病组;选取相应年龄段尾静脉空腹血糖低于 6.0 mmol/L,体质量正常的 db/ m 表型正常小鼠作为对照组.于相应年龄段取胰尾,透射电镜观察胰岛α细胞超微结构.结果:精尿病组胰岛α细胞胞质内分泌颗粒数量增多,可见致密芯与界膜间的间隙变窄,有的消失;线粒体和粗面内质网增多,细胞器结构未见明显改变.结论:胰岛α细胞超微结构改变和功能异常可能与Ⅱ型糖尿病的发病有关.     

Prenatal presentation and diagnosis of Baraitser‐Winter syndrome using exome sequencing

Baraitser‐Winter cerebrofrontofacial syndrome (BWCFF) is a rare autosomal dominant developmental disorder associated with missense mutations in the genes ACTB or ACTG1. The classic presentation of BWCFF is discerned by the combination of unique craniofacial characteristics including ocular coloboma, intellectual disability, and hypertelorism. Congenital contractures and organ malformations are often present, including structural defects in the brain, heart, renal, and musculoskeletal system. However, there is limited documentation regarding its prenatal presentation that may encourage healthcare providers to be aware of this disorder when presented throughout pregnancy. Herein we describe a case of a pregnancy with large cystic hygroma and omphalocele. Whole exome sequencing (WES) was performed and a de novo, heterozygous, likely pathogenic mutation in ACTB was detected, c.1004G>A (p.Arg335His), conferring a diagnosis of BWCFF.     

小胶质细胞极化介导炎症反应在脊髓损伤中的作用

背景:小胶质细胞极化参与脊髓损伤后的炎症反应,并在其中发挥关键作用。相关研究表明,有效诱导小胶质细胞从M1促炎表型向M2抗炎表型极化,可以减轻脊髓损伤后的炎症反应,促进组织的修复再生和神经功能的恢复。目的:文章对小胶质细胞的功能和极化、小胶质细胞极化对脊髓损伤的影响及其潜在调控策略以及脊髓损伤后炎症反应进行综述。方法:检索PubMed、Web of Science和中国知网数据库,英文检索词为“microglia,polarization,spinal cord injury,inflammation”,中文检索词为“小胶质细胞、极化、脊髓损伤、炎症”,按纳入和排除标准共纳入80篇文献进行总结。结果与结论:①由小胶质细胞介导的稳定而持续的炎症反应,对脊髓损伤的预后至关重要。②在生理条件下,小胶质细胞处于M0静止表型,但在脊髓损伤后,小胶质细胞活化,进而极化成M1促炎表型,导致神经组织修复能力降低和出现持续性神经炎症。③在脊髓损伤的炎症反应过程中,调控小胶质细胞向M2表型极化或至少向M2表型倾斜,有利于抑制氧化应激反应、调节突触重塑、促进轴突再生和血管生成,是一种有效的调控策略。④截止到目前的研究表明,间充质干细胞、外泌体、临床药物、天然产物、miRNAs和靶点分子可调控小胶质细胞在M1和M2表型之间的转换,这为脊髓损伤后神经组织的修复提供了一种新的思路,未来需进一步研究小胶质细胞在脊髓损伤过程中调控极化的详细机制。     

Orthofix-微型外固定器治疗Bennett骨折31例

目的分析应用Orthofix-微型器治疗第一掌骨基底部Bennett骨折的临床疗效。方法收集2009年1月~2013年1月我院31例采用Orthofix-微型器治疗的第一掌骨基底部Bennett骨折患者。记录患者年龄、性别等基线资料,以及术后上肢臂、肩、手功能调查量表(Disabilities of the arm,shoulder and hand,DASH)评分,随访终末期采用指总关节活动度(Total action movement,TAM)评分。结果随访6~24个月,平均14.4月,手术时间为18~40分钟,平均29.1分钟,术中出血量10~30m L,平均14.5m L。术后3月、术后6月及终末期DASH评分之间比较,差异均有统计学意义(0.05)。随访终末期,其中26例解剖复位,5例骨折对线良好,TAM评分优22例,良7例,差2例。随访期间未发生桡神经浅支损伤、钉道感染等并发症。结论 Orthofix-微型外固定器治疗Bennett骨折操作简单、疗效满意。     

Phorbol ester-induced inhibition of potassium currents in rat sensory neurons requires voltage-dependent entry of calcium

The whole cell patch-clamp technique was used to examine the effects of protein kinase C (PKC) activation (via the phorbol ester, phorbol 12,13 dibutyrate, PDBu) on the modulation of potassium currents (I(K)) in cultured capsaicin-sensitive neurons isolated from dorsal root ganglia from embryonic rat pups and grown in culture. PDBu, in a concentration- and time-dependent manner, reduced I(K) measured at +60 mV by approximately 30% if the holding potential (V(h)) was -20 or -47 mV but had no effect if V(h) was -80 mV. The PDBu-induced inhibition of I(K) was blocked by pretreatment with the PKC inhibitor bisindolylmaleimide I and I(K) was unaffected by 4-alpha phorbol, indicating that the suppression of I(K) was mediated by PKC. The inhibition of I(K) by 100 nM PDBu at a V(h) of -50 mV was reversed over several minutes if V(h) was changed to -80 mV. In addition, intracellular perfusion with 5 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) or pretreatment with omega-conotoxin GVIA or Cd(2+)-Ringer, but not nifedipine, prevented the PDBu-induced suppression of I(K) at -50 mV, suggesting that a voltage-dependent influx of calcium through N-type calcium channels was necessary for the activation of PKC. The potassium channel blockers tetraethylammonium (TEA, 10 mM) and 4-aminopyridine (4-AP, 3 mM and 30 microM) reduced I(K), but only TEA attenuated the ability of PDBu to further inhibit the current, suggesting that the I(K) modified by PDBu was sensitive to TEA. Interestingly, in the presence of 3 mM or 30 microM 4-AP, 100 nM PDBu inhibited I(K) when V(h) was -80 mV. Thus 4-AP promotes the capacity of PDBu to reduce I(K) at -80 mV. We find that activation of PKC inhibits I(K) in rat sensory neurons and that voltage-dependent calcium entry is necessary for the development and maintenance of this inhibition.     

Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument

The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm(-1) at 758 nm and 0.06 cm(-1) at 830 nm, and it was nearly consistent between piglets. The origin of this 'effective' background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.     

树鼩脑干儿茶酚胺神经元的分布

应用FAGLU荧光组化技术观察了树鼩脑干儿茶酚胺神经元(简称CA神经元)的位置分布及其形态特征。结果表明,CA神经元主要分布于下列核区:延髓的腹外侧网状核(LRN),孤束核(Sol);脑桥的面神经核(nVll).脑桥尾侧网状校(PnC),第四脑室顶外侧壁,蓝斑(Lc),脑桥头端与中脑尾端移行部的中缝背核(DR)、中央上核(cs),腹外侧臂旁核(VLPB)、中央灰质腹侧(Vcg);中脑的黑质(SN)、和腹侧被盖区(VTA)。     

氧化修饰引起脂蛋白（a）结构和生化特性变化

本文观察了体外丙二醛（ＭＤＡ），铜离子（Ｃｕ２＋氧化修饰的脂蛋白（ａ）［Ｌｐ（ａ）］结构和生物学性质的变化。氧化修饰Ｌｐ（ａ）过氧化程度增高，负电荷增加，易被巨噬细胞—清道夫受体识别和摄取。ＭＤＡ修饰Ｌｐ（ａ）出现新的ＭＤＡ－ＬＤＬ位点；同纤维蛋白溶酶原（Ｐｇ）竞争抑制试验显示氧化、修饰Ｌｐ（ａ）同Ｐｇ同源性增加。提示载脂蛋白（ａ）状态同动脉粥样硬化的病理过程有关。