We examined the relation of invasive pneumococcal disease to season, atmospheric conditions, and the rate of respiratory virus isolation in a community-wide surveillance program in Houston. Among adults, the number of cases of pneumococcal bacteremia peaked in midwinter and declined strikingly in midsummer, indicating a high degree of inverse correlation with the ambient temperature. We detected significant correlations between the occurrence of pneumococcal disease and the isolation of respiratory syncytial virus (P < .001), influenza virus (P < .001), and all viruses except influenza virus (P < .001), as well as with air pollution, as measured by SO2 levels (P < .001). In contrast, the rate of invasive pneumococcal disease among infants and children was relatively more sustained from October through May, with a notable decrease in summer months; the incidence of pneumococcal disease was therefore less strongly correlated with cold weather and less closely associated with the isolation of respiratory syncitial virus or influenza virus. However, pneumococcal disease among infants and children was associated with isolation of these viruses after a 4-week lag period as well as with isolation of adenovirus and ragweed pollen counts. The finding, with regard to children, that correlations tended to be stronger for events that occurred 1 month previously than for those that occurred contemporaneously is consistent with the concept that viral or allergic events predispose to otitis media with effusion, which becomes suppurative and leads to pneumococcal bacteremia or meningitis. For adults, a more immediate predisposition to pneumococcal pneumonia and bacteremia because of viral infection or air pollution was suggested.

No abstract

Paradoxical seizure exacerbation by anti-epileptic medication is a well-known clinical phenomenon in epilepsy, but the cellular mechanisms remain unclear. One possibility is enhanced network disinhibition by unintended suppression of inhibitory interneurons. We investigated this hypothesis in the stargazer mouse model of absence epilepsy, which bears a mutation in stargazin, an AMPA receptor trafficking protein. If AMPA signaling onto inhibitory GABAergic neurons is impaired, their activation by glutamate depends critically upon NMDA receptors. Indeed, we find that stargazer seizures are exacerbated by NMDA receptor blockade with CPP (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid) and MK-801, whereas other genetic absence epilepsy models are sensitive to these antagonists. To determine how an AMPA receptor trafficking defect could lead to paradoxical network activation, we analyzed stargazin and AMPA receptor localization and found that stargazin is detected exclusively in parvalbumin-positive (PV +) fast-spiking interneurons in somatosensory cortex, where it is co-expressed with the AMPA receptor subunit GluA4. PV + cortical interneurons in stargazer show a near twofold decrease in the dendrite:soma GluA4 expression ratio compared to wild-type (WT) littermates. We explored the functional consequence of this trafficking defect on network excitability in neocortical slices. Both NMDA receptor antagonists suppressed 0 Mg 2 +-induced network discharges in WT but augmented bursting in stargazer cortex. Interneurons mediate this paradoxical response, since the difference between genotypes was masked by GABA receptor blockade. Our findings provide a cellular locus for AMPA receptor-dependent signaling defects in stargazer cortex and define an interneuron-dependent mechanism for paradoxical seizure exacerbation in absence epilepsy.

Increasing data suggest that glutamate might act as a cell-signaling molecule in non-neuronal tissues such as the skin. Here we demonstrate the presence of functional N-methyl-D-aspartate (NMDA)-type glutamate receptors in human keratinocytes. NMDA receptor expression strongly reflects the degree of cell-to-cell contact. Wounding polarizes the expression of NMDA receptors in keratinocytes involved in re-epithelialization, and the process of re-epithelialization is inhibited by NMDA receptor activation. We also demonstrate that squamous cell carcinomas lack NMDA receptors. Our data suggest that Ca2+ entry through NMDA receptors influences the cycle of keratinocyte proliferation, differentiation, and migration during epithelialization. Moreover, NMDA receptor activation might play a role in contact-mediated inhibition of growth, a process that is absent during neoplastic pathology. This receptor may serve as a pharmacological target for modulating keratinocyte behavior and treating cutaneous disorders.