家兔失神经支配腓肠肌肌纤维退行性变与修复性再生的超微结构观察

目的:观察家兔腓肠肌失神经支配后肌纤维在退行性变与修复性再生过程中超微结构的变化,探讨失神经支配骨骼肌修复性再生障碍的机制。方法:实验于2005-04/2006-04在南方医科大学中心实验室完成。选择成年新西兰大白兔20只,切断一侧胫神经腓肠肌肌支,术后1,4,8,12,16周分别采用耳缘静脉注射空气处死4只。取实验侧和对照侧腓肠肌内侧头肌组织少许,用于制备超薄切片标本,透射电镜观察各时间点兔失神经腓肠肌肌纤维形态。结果:纳入动物20只,均进入结果分析。①正常家兔腓肠肌肌原纤维排列整齐,肌小节和Z线清晰,线粒体均匀分布在肌原纤维之间,排列规则,细胞核位于质膜周边,未见溶酶体。②失神经支配1周,肌原纤维排列基本整齐,线粒体增多,无明显肿胀。③失神经支配4周,线粒体明显增多肿胀,部分线粒体空泡样变,溶酶体增多,Z线模糊,肌原纤维间隙增大。④失神经支配8周,肌纤维明显萎缩退行性变,大部分肌原纤维消失,残留的肌原纤维变得模糊,间隙增大,肌小结丧失正常的结构,胞浆内含有大量空泡变性的细胞器,可发现畸形核,染色质浓缩、边集,肌细胞膜极度皱缩。镜下发现较多的位于基膜下活化的肌卫星细胞,细胞内含有发达的粗面内质网和丰富的胞浆。一些肌卫星细胞直接与肌纤维融合。同时在间质中可发现一些形态上很象成纤维细胞的细胞,不过这些细胞含有大量的粗面内质网,胞浆内有颗粒和微丝,少量的圆形的线粒体。在退行性变的肌纤维基膜下也可发现肌管样结构的再生肌细胞,在这些肌管内一些肌丝在一起聚集成束,没有组装成肌原纤维,没有正常的肌小结结构。在它们周围有细小的空肌管样结构,可能是以往再生的肌细胞退行性变后的残余体。在间质中可发现一些细小的肌纤维。⑤失神经支配12周,大部分肌纤维萎缩退行性变,但是仍可发现没有萎缩的肌纤维,这些肌纤维细胞核位于周边,有良好的收缩系统,纤维排列规则,Z线清晰,有完整的肌膜。⑥失神经支配16周,肌卫星细胞的数量明显减少,并可发现大量细小的肌纤维,多分布在较大的肌纤维附近,肌膜完整平滑,无皱褶。可发现核位于中央的肌纤维,胞浆内肌原纤维结构清楚,但是肌原纤维的排列远不如核位于周边的肌纤维整齐,说明其收缩系统发育不良。结论:失神经支配后肌细胞退行性变和修复性再生同时存在,再生的肌细胞不能,化发育为成熟的肌纤维,进而发生退行性变。长时间失神经支配,肌卫星细胞的耗竭是失神经支配骨骼肌晚期的主要超微结构变化。     

颅内动脉瘤栓塞后并发脑缺血的原因分析

1 临床资料我们总结2004-02/2004-06在第四军医大学唐都医院神经外科住院行栓塞治疗颅内动脉瘤患者27(男12,女15)例,年龄32～72岁.     

Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.     

High prevalence of HIV infection among homeless and street-involved Aboriginal youth in a Canadian setting

Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth. We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline, 15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection (odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants (p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention among Aboriginal young people are urgently required.     

Accuracy of passive ankle joint positioning during quiet stance in young and elderly subjects

Age-related postural deficits elicit compensatory mechanisms such as ankle dorsiflexion in the elderly. To gain further insight into this problem, the ability to match an ankle angle during quiet stance was studied in 12 elderly and 12 young subjects. Following an initial single limb angular perturbation presented in the ±4° range, a subject had to return a tilt platform to level, as determined by the nonperturbed limb. Elderly subjects exhibited significant positive (0.9°) over-shoot of the level position, in contrast to young subjects who matched ankle angle with a mean error of −0.1°. The elderly group also exhibited an increase in positioning error for angular displacements in the range between −1 and +1°. The results document age-related postural changes in ankle positioning which might affect postural stability in older adults.     

CD4 mimetics sensitize HIV-1-infected cells to ADCC

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection.Worldwide, it is estimated that more than 35 million people are living with HIV. In 2013 alone, around 2.1 million people became newly infected with HIV, and 1.5 million people died from AIDS (1). Measures to prevent HIV-1 transmission are desperately needed. Prevention of HIV-1 transmission and progression likely requires approaches that can specifically target and eliminate HIV-1-infected cells. Interestingly, there is increasing evidence supporting a role of antibody (Ab)-dependent cell-mediated cytotoxicity (ADCC) in controlling HIV-1 transmission and disease progression (2–8). Analysis of the correlates of protection in the RV144 vaccine trial suggested that increased ADCC activity was linked with decreased HIV-1 acquisition (9), and Abs with potent ADCC activity were isolated from some RV144 vaccinees (10). Recent studies reported that the viral accessory proteins Nef and Vpu protect HIV-1-infected cells from anti-HIV-1 envelope (Env)-mediated ADCC responses (11–14). Importantly, we and others reported that Env in the CD4-bound conformation was preferentially targeted by ADCC-mediating Abs and sera from HIV-1-infected individuals (11, 12, 15, 16), which represent a significant proportion of anti-Env Abs elicited during natural HIV infection (11, 17). However, the vast majority of circulating HIV-1 strains worldwide express functional Nef and Vpu proteins, which limit the exposure of CD4-induced (CD4i) Env epitopes at the surface of infected cells, likely preventing ADCC responses.Theoretically, agents promoting the CD4-bound Env conformation should expose CD4i epitopes that are readily recognized by ADCC-mediating Abs and sera from infected individuals (11, 12, 15, 16, 18), resulting in the sensitization of HIV-1-infected cells to ADCC. Importantly, modulating Env conformation at the surface of HIV-1-infected cells has become feasible as a result of the availability of small CD4-mimetic compounds (CD4mc). The prototypes of such compounds, NBD-556 and NBD-557, were discovered in a screen for inhibitors of gp120-CD4 interaction (19). These small-molecule ∼337-Da compounds and recent derivatives (DMJ-I-228, JP-III-48) bind in the Phe-43 cavity (20–22), a highly conserved ∼150-ų pocket in the gp120 glycoprotein located at the interface of the inner domain, outer domain, bridging sheet, and CD4 receptor (23). CD4mc block gp120-CD4 interaction and induce thermodynamic changes in gp120 similar to those observed during CD4 or soluble CD4 (sCD4) binding (24). Accordingly, these small molecules, as well as sCD4, can promote the transition of Env to the CD4-bound conformation, thus sensitizing HIV-1 particles to neutralization by otherwise nonneutralizing CD4i Abs (17, 25). Additional strategies using scaffolded miniproteins targeting critical gp120 elements required for CD4 interaction allowed the identification of CD4 mimetics with nanomolar affinity for gp120 (26). One of these variants, M48U1, displayed remarkably potent neutralization of three HIV-1 isolates (27). Its crystal structure in complex with HIV-1 gp120 was recently solved, showing that M48U1 engages the Phe-43 cavity in a manner similar to that of CD4 (28); thus, M48U1 might induce gp120 to adopt the CD4-bound conformation and expose CD4i epitopes. Previous studies exploring the antiviral properties of CD4mc were performed on viral particles (17, 25, 27). However, whether these compounds are able to engage the large amounts of Env present at the surface of infected cells and modulate Env conformation in a way that allows exposure of ADCC-mediating epitopes is currently not known. In this study, we show that CD4mc strongly sensitize HIV-1-infected primary CD4 T cells to ADCC mediated by sera, cervicovaginal fluids, and breast milk from HIV-1-infected individuals, as well as help eliminate infected, ex vivo-expanded primary CD4 T cells from HIV-1-infected individuals. Therefore, CD4mc possess three valuable complementary antiviral properties: direct inactivation of viral particles, sensitization of viral particles to neutralization by otherwise nonneutralizing Abs, and sensitization of HIV-1-infected cells to ADCC-mediated killing.     

股骨柄假体表面多孔层孔隙形状改造的动物实验

目的:观察菱形孔隙及方形孔隙两种不同几何形状多孔层设计股骨柄假体的生物学固定效果,分析孔隙几何形状对假体生物学固定的影响。方法:于2003-03/2004-04在中山大学医学部动物中心完成全部实验过程。纳入24只成年杂种犬,雌雄不拘,以随机数字表法均分为2组,即菱形孔隙组及方形孔隙组,各12只。自行设计完成犬骨重建型股骨柄假体,将股骨柄假体近2/3段表层改成两种不同几何形状的粗大多孔层结构,钛丝表面假体,钛丝直径改为1.0mm,孔径加大至5.0mm,孔隙度可达80%。菱形孔隙组钛丝沿股骨假体柄呈螺旋形排列并斜形相交,方形孔隙组钛丝沿股骨假体柄纵横排列并直角相交。均将假体表面孔隙内充填自体股骨头颈骨质制成的骨泥后,行右侧人工股骨头置换术。术后6个月行X射线摄片、组织学检查及生物力学测试,以股骨近端骨吸收情况、新生骨长入深度及孔隙充满度、假体-骨界面最大剪切强度测量为评价指标,了解假体内外成骨和固定情况。结果:菱形孔隙组及方形孔隙组各12只,实验中手术不成功或术后生存不够观察时间的均予实验过程中随时补足,最终每组12只进入结果分析。①组织学观察显示菱形孔隙组多孔层孔隙内最大骨长入深度及孔隙内新生骨平均充盈率均优于方形孔隙组(3000,2450μm;96.2%,71.6%)。②菱形孔隙组假体-骨界面最大剪切强度高于方形孔隙组,差异有显著性意义[(8.57±0.51),(3.15±0.41)N/mm2,P<0.01]。③菱形孔隙组6个月标本肉眼及X射线观察股骨近端无明显骨吸收,优于方形孔隙组;所有实验犬术后伤口缝线任其自行脱落,除1只伤口感染并于术后17d死亡外,余实验犬均伤口愈合良好,未出现不良反应。结论:股骨柄假体表面不同几何形状多孔层设计能影响其生物学固定效果,菱形孔隙设计优于方形孔隙。     

Abnormal pregnancy: early diagnosis by US and serum chorionic gonadotropin levels

Simultaneous sonography and quantitative serum human chorionic gonadotropin (HCG) levels from 126 women with threatened abortion were compared. Of 56 women with normal outcome, 39 (70%) had a gestation sac greater than or equal to 5 mm in mean sac diameter, and in each case the HCG level was 1,800 milli-international units (mIU/ml) or greater. The serum HCG levels strongly correlated with the gestation sac sizes to a mean sac diameter of 25 mm. Of 70 abnormal pregnancies, 31 demonstrated a gestation sac. Of these, 20 women (65%) had disproportionately low HCG levels relative to sac size, including 12 in whom the HCG level was less than 1,800 mIU/ml. One woman with an early molar pregnancy had a disproportionately elevated HCG level. Correlation of sonograms with a simultaneous measurement of serum HCG level is a useful method for evaluating threatened spontaneous abortion. A disproportionately low HCG level relative to gestation sac size is evidence for an abnormal pregnancy.