The transcriptional responses of respiratory epithelial cells to Bordetella pertussis reveal host defensive and pathogen counter-defensive strategies.

Bordetella pertussis, the causative agent of whooping cough, has many well-studied virulence factors and a characteristic clinical presentation. Despite this information, it is not clear how B. pertussis interaction with host cells leads to disease. In this study, we examined the interaction of B. pertussis with a human bronchial epithelial cell line (BEAS-2B) and measured host transcriptional profiles by using high-density DNA microarrays. The early transcriptional response to this pathogen is dominated by altered expression of cytokines, DNA-binding proteins, and NFkappaB-regulated genes. This previously unrecognized response to B. pertussis was modified in similar but nonidentical fashions by the antiinflammatory agents dexamethasone and sodium salicylate. Cytokine protein expression was confirmed, as was neutrophil chemoattraction. We show that B. pertussis induces mucin gene transcription by BEAS-2B cells then counters this defense by using mucin as a binding substrate. A set of genes is described for which the catalytic activity of pertussis toxin is both necessary and sufficient to regulate transcription. Host genomic transcriptional profiling, in combination with functional assays to evaluate subsequent biological events, provides insight into the complex interaction of host and pathogen.

A spiking network model of short-term active memory.

Studies of cortical neurons in monkeys performing short-term memory tasks have shown that information about a stimulus can be maintained by persistent neuron firing for periods of many seconds after removal of the stimulus. The mechanism by which this sustained activity is initiated and maintained is unknown. In this article we present a spiking neural network model of short-term memory and use it to investigate the hypothesis that recurrent, or "re-entrant," networks with constant connection strengths are sufficient to store graded information temporarily. The synaptic weights that enable the network to mimic the input-output characteristics of an active memory module are computed using an optimization procedure for recurrent networks with non-spiking neurons. This network is then transformed into one with spiking neurons by interpreting the continuous output values of the nonspiking model neurons as spiking probabilities. The behavior of the model neurons in this spiking network is compared with that of 179 single units previously recorded in monkey inferotemporal (IT) cortex during the performance of a short-term memory task. The spiking patterns of almost every model neuron are found to resemble closely those of IT neurons. About 40% of the IT neuron firing patterns are also found to be of the same types as those of model neurons. A property of the spiking model is that the neurons cannot maintain precise graded activity levels indefinitely, but eventually relax to one of a few constant activities called fixed-point attractors. The noise introduced into the model by the randomness of spiking causes the network to jump between these attractors. This switching between attractor states generates spike trains with a characteristic statistical temporal structure. We found evidence for the same kind of structure in the spike trains from about half of the IT neurons in our test set. These results show that the behavior of many real cortical memory neurons is consistent with an active storage mechanism based on recurrent activity in networks with fixed synaptic strengths.

Elevated plasma renin activity associated with renal dysfunction.

Elevated plasma renin activity (PRA) has been documented in patients with established acute renal failure. To study the association of PRA and renal dysfunction, 53 patients who were at risk of developing acute renal failure had serial measurements of PRA, renal function, and urinary beta 2-microglobulin. Those entered for study had pneumonia, septicaemia, volume loss with hypotension, or major surgical procedures with complications. Patients were divided into groups of abnormal or normal renal function. Abnormal renal function was defined by an elevated plasma urea and/or creatinine level with a submaximal urine urea to plasma urea ratio. The mean values of PRA for the abnormal and normal renal function groups, respectively, were 29 and 5.2 ng/ml/h (p less than 0.0001) and for beta 2-microglobulin 16.2 and 6.4 micrograms/l X 10(3) (p less than 0.0005). A linear regression of the logs of PRA to beta 2-microglobulin for the total group of patients gave an r value of 0.526 (p less than 0.001). These data show an association of PRA to renal dysfunction and tubular injury/dysfunction in the prerenal phase of renal failure, suggesting an effect of the renin-angiotensin system at this phase. It is not possible, however, to conclude from our study that the renin-angiotensin system has a direct role in the development of established acute tubular necrosis, since only 3 patients fell within this category.

Ceftazidime and cefamandole in the treatment of pneumonia.

Fifty-nine community-acquired pneumonias were treated in a randomized double blind trial with cefamandole or ceftazidime. A prospective scoring system was used to define severity. This made use of basic clinical data, associated diseases, white blood count, blood gases and chest radiographs. There were no serious side-effects from the drugs. There were two deaths and six failed treatment. The scoring system which defined an 'ill group' showed as good a response of these ill patients to the new cephalosporin, ceftazidime as to cefamandole.