p38丝裂原活化蛋白激酶信号途径在鼠破骨细胞生成和骨吸收中的作用

目的研究p38丝裂原活化蛋白激酶(p38MAPK)信号途径在甲状旁腺素相关肽(PTHrP)诱导的破骨细胞生成和骨吸收中的作用。方法取小鼠骨髓细胞,在PTHrP(45ng/ml)的刺激下,在不同试验组中分别入0.1、1.0及10μmol/L的p38MAPK抑制剂Fr167653,继续培养6d。抗酒石酸染色,进行破骨细胞计数。在小鼠颅骨部位注射PTHrP建立骨吸收和高钙血症动物模型。每日给予p38MAPK抑制剂Fr16765330mg/kg,每日2次,X线片观察骨吸收面积,组织学检查计算单位面积内破骨细胞数目,采集血样观察全血内游离钙水平。结果PTHrP刺激下,大量破骨细胞生成(118.9±28.3)个/孔;加入0.1μmol/LFr167653可以部分抑制破骨细胞的生成(79.6±28.0)个/孔,加入10μmol/LFr167653几乎全抑制了破骨细胞生成(7.4±0.4)个/孔,每日给予Fr16765330mg/kg,每日2次,可以明显抑制骨吸收,表现为X线片上骨吸收面积减少,单位面积内破骨细胞数目减少,但是并不能有效地抑制高钙血症。结论抑制p38MAPK信号途径可以抑制破骨细胞的分化和局部骨吸收。     

JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps

Recent studies have shown that drug‐induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross‐modal correlation of MRI‐based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma‐aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson''s disease patients (PD) and risperidone‐induced changes in rsfMRI and cerebral blood flow (CBF). Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD and dopaminergic (D2) and serotonergic systems (5‐HT1b). Risperidone induced CBF alterations were correlated with its main targets in serotonergic and dopaminergic systems. JuSpace provides a biologically meaningful framework for linking neuroimaging to underlying neurotransmitter information.     

High resolution copy number analysis of IRF4 translocation‐positive diffuse large B‐cell and follicular lymphomas

Translocations affecting chromosome subband 6p25.3 containing the IRF4 gene have been recently described as characteristic alterations in a molecularly distinct subset of germinal center B‐cell‐derived lymphomas. Secondary changes have yet only been described in few of these lymphomas. Here, we performed array‐comparative genomic hybridization and molecular inversion probe microarray analyses on DNA from 12 formalin‐fixed paraffin‐embedded and two fresh‐frozen IRF4 translocation‐positive lymphomas, which together with the previously published data on nine cases allowed the extension of copy number analyses to a total of 23 of these lymphomas. All except one case carried chromosomal imbalances, most frequently gains in Xq28, 11q22.3‐qter, and 7q32.1‐qter and losses in 6q13‐16.1, 15q14‐22.31, and 17p. No recurrent copy‐neutral losses of heterozygosity were observed. TP53 point mutations were detected in three of six cases with loss of 17p. Overall this study unravels a recurrent pattern of secondary genetic alterations in IRF4 translocation‐positive lymphomas. © 2012 Wiley Periodicals, Inc.     

Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T- lymphocyte lineage

The existence and characteristics of bone marrow T-cell progenitors have not yet been established in man. Several pieces of evidence such as the reconstitution of certain immunodeficiencies by bone marrow graft suggest that T-cell precursors are present in the bone marrow. We report the growth of T-cell colonies from bone marrow populations using PHA-stimulated lymphocyte-conditioned medium containing T-cell growth factor (TCGF). Rosetting experiments and complement-dependent cytotoxicity assays with monoclonal antibodies indicate that the bone marrow T colony-forming cells (T-CFC) are E- OKT 3- and la+, i.e., immature progenitors. The colonies derived from these cells have the phenotype of mature T cells: E + OKT 3 + la- with either helper (OKT 4+) and suppressor (OKT 8 +) antigens. These results suggest that a thymic microenvironment may not be necessary for the in vitro proliferation and differentiation of the T-cell lineage in adult humans. These methodologies may permit direct investigation of early phenomena concerning the T-cell lineage, such as the acquisition of self-tolerance, the formation of a repertoire of specificities, and the HLA restriction phenomena that we believe takes place before the thymic maturation.     

Minor histocompatibility antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T-cell clones inhibit human hematopoietic progenitor cell growth by a mechanism that is dependent on direct cell-cell contact

HLA-identical bone marrow transplantation (BMT) may be complicated by graft-versus-host disease or graft rejection. Both complications are thought to be initiated by recognition of minor histocompatibility (mH) antigens by HLA-restricted mH-antigen-specific T lymphocytes. Using HLA- A2-restricted mH antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T lymphocyte (CTL) clones, we studied the recognition by these CTL clones of interleukin-2 (IL-2)-stimulated T cells (IL-2 blasts), BM mononuclear cells (BMMNCs), and hematopoietic progenitor cells (HPCs). We showed that, when IL-2 blasts from the BM donors who were investigated were recognized by the HA-1-, -2-, and -4-, and HY- specific CTL clones, their BMMNCs and HPCs were recognized as well by these CTL clones, resulting in antigen-specific growth inhibition of erythrocyte burst-forming units (BFU-E), colony-forming units- granulocyte (CFU-G), and CFU-macrophage (CFU-M). the HA-2-specific CTL clone, however, inhibited BFU-E and CFU-G growth from four donors to a lesser extent than from two other donors. We further investigated whether inhibitory cytokines released into the culture medium by the antigen-specific stimulated CTLs or by stimulated BMMNCs were responsible for suppression of HPC growth or whether this effect was caused by direct cell-cell contact between CTLs and HPCs. HPC growth inhibition was only observed after preincubation of BMMNCs and CTLs together for 4 hours before plating the cells in semisolid HPC culture medium. When no cell-cell contact was permitted before plating, neither antigen-stimulated CTL nor antigen-nonstimulated CTLs provoked HPC growth inhibition. Culturing BMMNCs in the presence of supernatants harvested after incubation of BMMNCs and CTL clones together for 4 or 72 hours did also not result in HPC growth inhibition. Both suppression of HPC growth and lysis of IL-2 blasts and BMMNCs in the 51Cr-release assay appeared to be dependent on direct cell-cell contact between target cells and CTLs and were not caused by the release of inhibitory cytokines into the culture medium by antigen-specific stimulated CTLs or by stimulated BMMNCs. Our results show that mH-antigen-specific CTLs can inhibit HPC growth by a direct cytolytic effect and may therefore be responsible for BM graft rejection after HLA-identical BMT.     

急性阑尾炎多层螺旋CT扫描征象与血清炎性标志物的相关性研究

目的探讨急性阑尾炎多层螺旋CT征象与血清炎性标志物的关系。方法收集2012年1月至2013年12月于同济大学附属杨浦医院经手术病理证实的具有完整临床及影像资料的急性阑尾炎患者66例,对所有患者的急性阑尾病变程度行CT分级,分析其与患者白细胞(WBC)计数、中性粒细胞百分比(NEUT%)及血清C反应蛋白(CRP)水平的相关性。结果急性阑尾炎CT分级与患者WBC计数与CRP水平呈正相关(P0.05),穿孔性阑尾炎患者NEUT%及CRP水平明显高于其他患者。CRP水平与阑尾直径、阑尾积液、回盲部变化、阑尾周围炎性条纹、小肠积液呈正相关(P0.05),WBC计数与回盲部变化及阑尾周围炎性条纹呈正相关(P0.05)。结论WBC计数及CRP水平与急性阑尾炎CT分级有关,CRP对急性阑尾炎的诊断及其严重程度的判断更有优势;CRP、NEUT%是穿孔性阑尾炎的重要预测因子,WBC可以更好地发现早期阑尾周围的炎性反应,综合分析CT表现与血清炎性标志物能更准确地诊断急性阑尾炎。     

肺炎支原体肺炎患儿肺泡灌洗液病菌量与临床特征相关性研究

目的研究肺炎支原体(MP)肺炎患儿肺泡灌洗液(BALF)中MP-DNA基因拷贝数和患儿病情严重程度的关系。方法选取河北省儿童医院2012年10月至2013年12月收治的82例MP肺炎患儿作为研究对象,行支气管镜下支气管肺泡灌洗(BAL),采用荧光实时定量聚合酶链反应(FQ-PCR)对肺泡灌洗液中MP-DNA定量检测,并根据检测结果的基因拷贝数分为低菌量组(MP-DNA的拷贝数103/mL的患儿),中等菌量组(MP-DNA的拷贝数为103~106/mL的患儿)和高菌量组(MP-DNA的拷贝数106/mL的患儿)。比较不同菌量组患儿的临床症状、实验室检查结果和影像学结果。结果高菌量组患儿总病程长,高热患儿和热程大于或等于7d的患儿数量均多于中、低菌量组,使用大环内酯类药物后退热时间也较其他两组更长,差异均具有统计学意义(P=0.027、P=0.025、P=0.029、P=0.003)。实验室检查中高菌量组C反应蛋白值升高明显,高于中低菌量组,差异有统计学意义(P=0.005)。影像学检查中高菌量组大片肺实变、肺不张者较、低菌量组多(P=0.002)。低菌量组未见双侧胸腔积液或大量胸腔积液患儿,中高菌量组此症状患儿较多,差异有统计学意义(P=0.033)。结论 MP肺炎患儿BALF病菌量和临床表现密切相关,高菌量组患儿病情更为严重。可能与患儿体内的肺炎支原体不易清除和存在较强的免疫反应有关,临床需延长抗菌药物治疗时间以及加强免疫治疗。     

肠球菌医院感染特征及新型抗菌药物耐药性研究

目的探讨肠球菌属细菌分布及耐药性特征,为指导临床合理用药及控制医院感染提供依据。方法对该院2011年1月至2013年12月年临床送检标本进行细菌分离培养、鉴定和药敏试验。结果共检出肠球菌属细菌140株,屎肠球菌71株(50.7%),粪肠球菌60株(42.9%),其他肠球菌9株(6.4%),其中尿液99株(70.7%);粪肠球菌对青霉素、氨苄西林、红霉素的耐药率为15.0%、12.5%和75.0%,屎肠球菌对青霉素、氨苄西林、左氧氟沙星、环丙沙星、红霉素耐药率大于80.0%,粪肠球菌和屎肠球菌对万古霉素(5.0%、4.2%)、利奈唑胺(8.4%、1.4%)极度敏感,喹奴普丁/达福普丁对粪肠球菌耐药率(100.0%)高于屎肠球菌(26.7%),达托霉素无耐药菌株。结论肠球菌属以泌尿系统感染为主,屎肠球菌检出率略大于粪肠球菌,屎肠球菌对大多数抗菌药物耐药率高于粪肠球菌,喹奴普丁/达福普丁仅对屎肠球菌有较高敏感性,万古霉素、利奈唑胺、达托霉素对肠球菌属细菌保持极高敏感性。