Protein translocation: delivering virulence into the host cell

A wide variety of plant and human bacterial pathogens use a specialized 'type III' protein secretion system to deliver virulence factors into host cells. Appendage-like surface structures have recently been identified on several bacterial pathogens and there are indications that these may be conduits for virulence factor delivery.     

Chondrocyte apoptosis induced by aggrecan G1 domain as a result of decreased cell adhesion

A major feature of cartilage deterioration during joint injury and disease is aggrecan degradation and the loss of proteoglycan. Most of the degraded fragments are released into the circulatory system except the G1 domain which accumulates locally in the synovial fluid and cartilage because of its hyaluronan-binding ability. In this study, our objective was to investigate the effects of G1 accumulation on chondrocyte function. We chose to mimic the accumulation of G1 domain by developing a method to express G1 in chondrocytes. We transiently and stably expressed aggrecan G1 domain in the cells and tested the effects of G1 in cell adhesion and apoptosis. Overexpression of the G1 construct induced apoptosis in adherent chondrocytes but not in chondrocytes maintained in suspension cultures. Higher levels of G1 expression caused greater reduction in cell-substratum interaction and induced more cell death. The effect was dose dependent. To corroborate our findings, the role of G1 in reducing adhesion and inducing apoptosis was further investigated in fibroblasts. We found that low adherent cultures also had high levels of apoptosis. Our results suggest that G1 induced apoptosis by destabilizing cell-substratum interaction.     

Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis

The effect of Mycobacterium tuberculosis infection on the viability of healthy (control) human alveolar macrophages was evaluated by staining with ethidium homodimer and calcein to discriminate live from dead cells. Infection with M. tuberculosis H37Ra or H37Rv increased macrophage mortality at 6 days from the control level of 3.8% +/- 0.7% to 28.7% +/- 6.9% or 12.6% +/- 3.1%, respectively (P < 0.001 for comparisons of all conditions). A role for tumor necrosis factor alpha (TNF-alpha) in the M. tuberculosis-induced cytolysis of alveolar macrophages was demonstrated by increased cytotoxicity following the addition of exogenous TNF-alpha to the cultures and by enhancement of macrophage survival when M. tuberculosis-infected alveolar macrophages were treated with pentoxifylline or anti-TNF-alpha antibody. The cytolytic mechanism was determined to be apoptosis by the demonstration of a characteristic internucleosomal ladder of genomic DNA by agarose gel electrophoresis, by finding nuclear fragmentation and condensation by electron microscopy, and by in situ terminal transferase-mediated nick end labeling of fragmented DNA in alveolar macrophages infected with M. tuberculosis in vitro. The latter technique was employed to reveal extensive apoptosis within caseating granulomas from lung tissue samples from clinical tuberculosis cases. The induction of apoptosis in alveolar macrophages by M. tuberculosis may play a role in the macrophage-pathogen interaction of tuberculosis in vivo.     

Midline dorsal appendages

A case of a mature posterior cervical teratoma resembling two fingers and a case of a lumbosacral limb are presented. These are at least the seventh and eighth reported paraspinous or occipital teratomas with recognizable extremity development. Both anomalies had intradural extension and required exploration to decrease the likelihood of future spinal cord tethering. Preoperative evaluation, surgical technique, postoperative follow-up, and review of the literature are presented.     

Reproductive pattern, perinatal mortality, and sex preference in rural Tamil Nadu, south India: community based, cross sectional study

OBJECTIVES: To study reproductive pattern and perinatal mortality in rural Tamil Nadu, South India. DESIGN: Community based, cross sectional questionnaire study of 30 randomly selected areas served by health subcentres. SETTING: Rural parts of Salem District, Tamil Nadu, South India. SUBJECTS: 1321 women and their offspring delivered in the 6 months before the interview. MAIN OUTCOME MEASURES: Number of pregnancies, pregnancy outcome, spacing of pregnancies, sex of offspring, perinatal and neonatal mortality rates. RESULTS: 41% of the women (535) were primiparous; 7 women (0.5%) were grand multiparous (> 6 births). The women had a mean age of 22 years and a mean of 2.3 pregnancies and 1.8 live children. The sex ratio at birth of the index children was 107 boys per 100 girls. The stillbirth rate was 13.5/1000 births, the neonatal mortality rate was 35.3/1000, and the perinatal mortality rate was 42.0/1000. Girls had an excess neonatal mortality (rate ratio 3.42%; 95% confidence interval 1.68 to 6.98; this was most pronounced among girls born to multiparous women with no living sons (rate ratio 15.48 (2.04 to 177.73) v 1.87 (0.63 to 5.58) in multiparous women with at least one son alive). CONCLUSIONS: In this rural part of Tamil Nadu, women had a controlled reproductive pattern. The excess neonatal mortality among girls constitutes about one third of the perinatal mortality rate. It seems to be linked to a preference for sons and should therefore be addressed through a holistic societal approach rather than through specific healthcare measures.