Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the brain

Streptococcus pneumoniae is the most common cause of bacterial meningitis of high mortality and morbidity. Neurological sequelae include paralysis, mental retardation, and learning disorders. In humans, neurons of the hippocampus undergo apoptosis as a result of meningitis. Phosphatidylcholine (PtdCho) is an essential component of mammalian cell membranes and PtdCho deficiency, either due to chemicals or altered nutrition, leads to apoptosis, especially in hippocampal neurons. We show that apoptosis of a variety of brain cells after pneumococcal infection arises from inhibition of PtdCho biosynthesis, the first such activity described for a bacterium. Apoptosis inhibitors did not prevent the bacterial-dependent inhibition of PtdCho biosynthesis. Supplementation with exogenous lyso-phosphatidylcholine prevents cell death and treatment of mice with cytidine diphosphocholine attenuates hippocampal damage during meningitis, even after the onset of infection. We conclude that bacterial inhibition of PtdCho biosynthesis activates an apoptotic cascade that is a causative event in pathogenesis and amenable to therapeutic intervention.     

Adherence of Bordetella pertussis to human respiratory epithelial cells

Adherence of Bordetella pertussis to ciliated respiratory tract mucosa is important in the pathogenesis of whooping cough. The adherence of B pertussis to human respiratory epithelial cells was investigated using cells obtained by brushing at bronchoscopy. B pertussis attached exclusively to the ciliary tufts of ciliated cells. A mean +/- SEM of 5.0 +/- 0.3 organisms attached per cell when bacteria in a concentration of 2 X 10(9)/ml were incubated with ciliated cells. Organisms examined by electron microscopy were found to adhere to the cilia both by direct apposition and by filaments coursing between bacteria and cilia. The specificity of the adherence of B pertussis to ciliary tufts may explain the unique ability of this organism to infect the human tracheobronchial mucosa.     

Cerebral cell adhesion molecule: a novel leukocyte adhesion determinant on blood-brain barrier capillary endothelium

The tight junctions of the cerebral capillary endothelium form the highly restrictive blood-brain barrier. Migration of leukocytes across this unique barrier may involve ligation of elements in addition to those of the fenestrated capillaries of the peripheral vascular system. An antibody raised against a bacterial adhesive protein and shown to have cross-reactivity with brain capillaries and to block leukocyte migration into the brain was used to identify and clone a novel determinant on brain microvessels. This cDNA was sequenced, and the expressed protein supported leukocyte adhesion in a CD18-dependent fashion. The high level of brain microvessel expression of this adhesion molecule, termed the cerebral cell adhesion molecule, implicates it in leukocyte transmigration across the blood-brain barrier.     

大鼠坐骨神经分支选择结扎切断模型的建立及脊髓背脚N-甲基-D-天冬氨酸受体检测

目的采用免疫组织化学方法,观察SNI模型大鼠脊髓背角神经元NMDAR的表达。方法健康雄性SD大鼠15只,随机分为3组：对照组（C1组）、假手术组（C2组）和生理盐水组（NS组）,每组5只。C1组不做任何处理,其他2组均根据改良Yaksh法进行鞘内置管。置管5d后,NS组按Woolf等方法建立神经病理性疼痛模型（SNI）,C2组除不损伤神经外处理同NS组;制模2d后,C2组和NS组用微量注射器鞘内注射20μL生理盐水,然后用生理盐水冲管（共20μL）。在30min后,C2组、NS组均进行疼痛行为学观察。3组均在注药后2h处死大鼠,用免疫组化法观察大鼠腰5节段水平脊髓背角NMDAR的表达。结果C1组和C2组在各时点均无机械性异常疼痛出现,热刺激后爪退缩潜伏时间差异也均无统计学意义（P〉0.05）;NS组在SNI手术后第1天和第2天出现明显的痛觉过敏（机械性异常疼痛痛阈降低）,与C1组比较差异有统计学意义（P〈0.01）,但对热刺激的后爪退缩潜伏时间与C1组比较差异无统计学意义（P〉0.05）;NS组大鼠脊髓背角NMDAR免疫阳性细胞数量与C1及C2组比较明显增加,两者之间差异有统计学意义（P〈0.05）;NS组的脊髓背角NMDAR免疫阳性细胞数密度值与C1,C2组相比显著增高（P〈0.05）,NS组的阳性细胞光密度值较C1组和C2组增高（P〈0.05）。结论SNI模型可引起大鼠损伤侧肢体机械性痛觉过敏,但对热刺激不敏感;SNI模型引起大鼠脊髓背角神经元NMDAR表达上调。     

Filamentous hemagglutinin of Bordetella pertussis: nucleotide sequence and crucial role in adherence.

Filamentous hemagglutinin is a surface-associated adherence protein of Bordetella pertussis, which is a component of some new acellular pertussis vaccines. The nucleotide sequence of an open reading frame that encompasses the filamentous hemagglutinin structural gene, fhaB, suggests that proteolytic processing is necessary to generate the mature 220-kDa filamentous hemagglutinin product. An Arg-Gly-Asp (RGD) tripeptide is found within filamentous hemagglutinin that may be involved in its adherence properties. An internal in-frame deletion in fhaB, encompassing the RGD region, causes loss of B. pertussis-binding to ciliated eukaryotic cells, confirming a potential role for this protein in host-cell binding and infection.     

Dynamic probabilistic model for determination of optimal timing of surveillance chest radiography in pediatric Hodgkin disease

A dynamic probabilistic model based on hazard rate analysis, Monte Carlo modeling, and lead-time estimation techniques was developed to determine the optimal timing and frequency of chest radiography in the monitoring for relapse of children with treated Hodgkin disease. The analysis incorporates the performance characteristics of chest radiography, the natural history of the disease process, and therapeutic efficacy as a function of earliness of detection in the determination of optimal strategy. Examples of the model applied to the experiences of Stanford Medical Center and St. Jude Children's Research Hospital illustrate the utility of such a model in customizing an optimal monitoring strategy for a specific institution and clinical experience. The results suggest that monitoring protocols significantly overutilize chest radiography in the evaluation for recurrent Hodgkin disease in children.