The flagellum protein flagellin of Listeria monocytogenes is encoded by the flaA gene. Immediately downstream of flaA, two genes, cheY and cheA, encoding products with homology to chemotaxis proteins of other bacteria, are located. In this study we constructed deletion mutants with mutations in flaA, cheY, and cheA to elucidate their role in the biology of infection with L. monocytogenes. The ⌬cheY, ⌬cheA, and double-mutant ⌬cheYA mutants, but not ⌬flaA mutant, were motile in liquid media. However, the ⌬cheA mutant had impaired swarming and the ⌬cheY and ⌬cheYA mutants were unable to swarm on soft agar plates, suggesting that cheY and cheA genes encode proteins involved in chemotaxis. The ⌬flaA, ⌬cheY, ⌬cheA, and ⌬cheYA mutants (grown at 24°C) showed reduced association with and invasion of Caco-2 cells compared to the wild-type strain. However, spleens from intragastrically infected BALB/c and C57BL/6 mice showed larger and similar numbers of the ⌬flaA and ⌬cheYA mutants, respectively, compared to the wild-type controls. Such a discrepancy could be explained by the fact that tumor necrosis factor receptor p55 deficient mice showed dramatically exacerbated susceptibility to the wild-type but unchanged or only slightly increased levels of the ⌬flaA or ⌬cheYA mutant. In summary, we show that listerial flaA, cheY, and cheA gene products facilitate the initial contact with epithelial cells and contribute to effective invasion but that flaA could also be involved in the triggering of immune responses.

Background and Purpose-Perinatal hypoxia-ischemia (HI) produces acute and prolonged inflammation of the brain.Mast cells (MCs), numerous in the pia and CNS of neonatal rats, can initiate inflammation attributable to preformed mediators. MCs contribute to HI brain damage in the neonatal rat; MC stabilization protects through 48 hours of reperfusion. Here we hypothesize that HI induces early MC migration, activation, and release of proinflammatory molecules. Methods-HI

Perinatal hypoxic-ischemic (HI) brain damage is a major cause of mortality and neurological morbidity in infants and children. Using an established model of unilateral hypoxia-ischemia in neonatal rats, the present study focused on mast cells (MCs), important regulators of inflammatory processes, as potential contributors to HI damage. MCs are present in the pia of the neonatal rat, entering the central nervous system (CNS) during cerebral development along penetrating blood vessels. Following hypoxia-ischemia, MC numbers increased dramatically in the ipsilateral (ischemic) hemisphere (p < 0.01). In animals exposed to hypoxia only, the numbers of MCs were elevated in both hemispheres to an extent equal to that observed in the contralateral hemisphere of HI animals (p < 0.05 vs. control). Within damaged areas (ipsilateral only), MCs were observed in regions of activated microglia and astroglia that characterize the ischemic hemisphere. Using a triple-label paradigm, MCs were observed along elongating blood vessels, some of which express the GLUT1 isoform of the glucose transporter protein, indicative of blood-brain barrier vessels. To determine whether MC activation has a role in HI brain damage, rat pups were treated with the MCs stabilizer, disodium cromoglycate (cromolyn),prior to and/or following hypoxia-ischemia. The cromolyn treatment inhibited MC migration into the CNS (p < 0.05) and limited brain damage more than 50% (p < 0.01) vs. saline controls. These data support the hypothesis that MCs are key contributors to the extent of brain damage due to hypoxia-ischemia in the immature animal.

The aim of this study was to analyse cognitive and motor function in a population-based sample of people with multiple sclerosis (PwMS), taking into account both disease-related data and sociodemographic factors. Data were collected from 166 PwMS during home visits. Cognitive function was assessed by the Mini-Mental State Examination (MMSE), the Free Recall and Recognition of 12 Random Words Test (FRR12RWT), and the Symbol Digit Modalities Test (SDMT); manual dexterity by the Nine-Hole Peg Test (NHPT); global motor capacity by the Lindmark Motor Capacity Assessment; and walking capacity by a timed 10-metre walk. On cognitive tests, 55% (MMSE), 84% (FRR12RWT), and 45% (SDMT) of PwMS scored within the normal range; 27% of PwMS displayed normal manual dexterity, 9% had a maximal motorcapacity score, and 8% walked at normal speed. Factors associated with normal cognitive function were lower disability and higher education; lower disability and current employment were predictive of capacity to perform the NHPT and to walk 10 metres. In conclusion, cognitive function was normal in approximately half of the PwMS investigated, while a minority displayed normal manual dexterity and normal walking capacity. Thus, both disease severity and sociodemographic factors appear to influence cognitive and motor function in MS.