Mechanisms of innate resistance to Toxoplasma gondii infection.

The interaction of protozoan parasites with innate host defences is critical in determining the character of the subsequent infection. The initial steps in the encounter of Toxoplasma gondii with the vertebrate immune system provide a striking example of this important aspect of the host-parasite relationship. In immuno-competent individuals this intracellular protozoan produces an asymptomatic chronic infection as part of its strategy for transmission. Nevertheless, T. gondii is inherently a highly virulent pathogen. The rapid induction by the parasite of a potent cell-mediated immune response that both limits its growth and drives conversion to a dormant cyst stage explains this apparent paradox. Studies with gene-deficient mice have demonstrated the interleukin-12 (IL-12)-dependent production of interferon gamma (IFN-gamma) to be of paramount importance in controlling early parasite growth. However, this seems to be independent of nitric oxide production as mice deficient in inducible nitric oxide synthase (iNOS) and tumour necrosis factor receptor were able to control early growth of T. gondii, although, they later succumbed to infection. Nitric oxide does, however, seem to be important in controlling persistent infection; treating chronic infection with iNOS metabolic inhibitors results in disease reactivation. Preliminary evidence implicates neutrophils in effector pathways against this parasite distinct from that described for macrophages. Once initiated, IL-12-dependent IFN-gamma production in synergy with other proinflammatory cytokines can positively feed back on itself to induce ''cytokine shock''. Regulatory cytokines, particularly IL-10, are essential to down-regulate inflammation and limit host pathology.     

Atopy predisposing to acute bronchiolitis during an epidemic of respiratory syncytial virus.

Thirty-one infants admitted to hospital with acute bronchiolitis during an epidemic of respiratory syncytial virus were compared with a control group of 32 infants to establish whether the two groups differed in atopic background. Past history of respiratory illness, eczema, and present reactions to skin testing differed significantly between the two groups. Thus, infants with acute bronchiolitis had a significantly higher atopic predisposition than the controls.     

Pathways controlling the superoxide response during phagocyte differentiation: involvement of arachidonic acid and Ca2+ in the response to bacterial endotoxin

Abstract In contrast to the phorbol ester oxidative response, which only develops during dimethyl-sulphoxide (DMSO)-induced differentiation of the human leukemic myeloblast HL-60 cell-line, the endotoxin response was observed in undifferentiated and differentiated cells. The Ca²⁺ response to endotoxin, detected in both differentiated and undifferentiated HL-60 cells, consisted of a transient 10–50 nM increase in intracellular Ca²⁺. A very slow, irreversible increase in intracellular Ca²⁺ was detected at high 1–100 μg/ml endotoxin concentrations, and this effect, and the inositol phosphate response, correlated with the surfactant activities of various endotoxins and Lipid A. Arachidonic acid and sodium arachidonate 1–50 μM stimulated a large 200–500 nM and transient Ca²⁺ response in undifferentiated HL-60 cells, which was significantly greater than that elicited by 1–50 μM eicosapentaenoic acid, and was not observed at similar concentrations of arachidonic acid methyl ester or myristic acid. These concentrations (1–50 μM) of arachidonic acid were observed to have surfactant activities on the plasma membrane. At lower arachidonic acid concentrations a marked potentiation of both Ca²⁺ and oxidative responses to the chemotactic peptide fMet-Leu-Phe was detected. It is possible that the arachidonic acid released during phospholipase A₂ activation of neutrophils may be involved in cellular cross-talk and, at higher concentrations, in directly activating Ca²⁺ and superoxide production. It is also possible that previously reported effects of endotoxin at high concentrations are an vitro artefact of surfactant properties of endotoxin.     

Fluid mechanics of blood flow in human fetal left ventricles based on patient-specific 4D ultrasound scans

The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic–systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts.