Robert C Read

..Human polymorphisms of Toll-like receptor genes have been discovered and are associated with hyporesponsiveness to bacterial components...

..From a clinical perspective, appropriate drugs include those that are stable to beta-lactamases, are bactericidal against causative pathogens, penetrate diseased lung tissue in high concentrations and have a good safety profile...

..A number of studies have shown that it is possible to stratify patients according to severity of illness, to in-patient or out-patient management protocols. These have been validated and refined...

..These data show that nasal immunisation with chitosan plus trivalent inactivated influenza is a potentially effective, easily-administered form of vaccination...

..The recently formed European Centre for Disease Prevention and Control in Stockholm, Sweden, will increase demands in areas of surveillance of infectious diseases and antimicrobial resistance on both specialties...

..Therefore, this functional TLR4 polymorphism does not influence susceptibility to or severity of meningococcal disease...

..06 mg/L) and a high-level PRSP clinical isolate (159; MIC 16 mg/L) following exposure to penicillin and cefotaxime...

..Diagnostic polymerase chain reaction (PCR) detection of Neisseria meningitidis has enabled accurate quantification of the bacterial load in patients with meningococcal disease...

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..These data suggest that tetraspanins are required for optimal function of epithelial adhesion platforms containing specific receptors for Neisseria meningitidis and potentially for multiple species of bacteria...

..The lack of swarming motility of the hmp mutant and its aflagellate state suggest that Hmp synthesis is a metabolic burden in the absence of NO-related stresses...

..coli. In each case, this effect was shown to be dependent on bacterial NO detoxification genes, which act to prevent SNO formation through the removal of NO. This may represent a novel mechanism of host cell injury by bacteria...

..Thus, the cellular responses to peroxynitrite and hydrogen peroxide are distinct...

..0385). There was a relative defect of T-cell responsiveness to T-cell-dependent antigen stimulation in MCC vaccine failures, which was manifested in reduced T-cell help to B cells...

..Addition of SNAP to cultures infected with wild-type mimicked the effect observed in cultures infected with the norB mutant. In conclusion, NorB-catalysed removal of NO modifies cellular release of NO-regulated cytokines and chemokines...

..Controls were derived from 1280 northern English blood donors...

..Bacteria exposed to concentrations of penicillin that cause lysis (MIC) or no lysis with morphological changes (sub-MIC) induce differential patterns of pro-inflammatory cytokine expression by human macrophages...

..CONCLUSIONS: beta-Lactam antibiotics induce surface changes and release of cell wall structures from bacteria that are proinflammatory via TLR2, but the glycopeptide vancomycin does not...

..These findings demonstrate that cathepsin D regulates multiple proteins controlling the mitochondrial pathway of macrophage apoptosis or competing death processes, facilitating intracellular bacterial killing...

..These results illustrate important roles for NO in the integration of host defense and regulation of inflammation in human macrophages...

..Variation in the genes of the surfactant proteins affects the expression and function of these molecules...

..Plasma and CSF genomic bacterial loads of non-B N. meningitidis serogroups correlated significantly. Serogroup B-infected patients with genotype TNF2 (-308A) had significantly higher CSF bacterial loads...

..These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function...

..This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation...

..Mcl-1 transgenic mice clear pneumococci from the lung less efficiently than nontransgenic mice. Dynamic changes in Mcl-1 expression determine macrophage viability as well as antibacterial host defense...

..coli and K. pneumoniae or bacterial stimulation of cell metabolism. In this regard, the fate of monocytes following bacterial challenge more closely resembles neutrophils than macrophages...

..Ageing is also associated with changes in the immune system including higher systemic levels of pro-inflammatory cytokines. Methylation of DNA is an important regulator of gene expression and changes with age...

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..Our findings indicate that the tetraspanins CD9, CD63 and CD81 are all involved in MGC formation, but play distinct roles...

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..In conclusion, this sample of CVID patients exhibits a defect of T-cell "help" to B cells, and/or B-cell response to T-cell help...

..The defect is not overcome by CD4(+) T cell assistance and may explain the relatively poor response to pneumococcal vaccination in survivors of invasive pneumococcal disease...

..We demonstrate that N. meningitidis prevents macrophage apoptosis via genes encoding nitric oxide detoxification and a porin, PorB...

..It will then go on to consider strategies for optimizing the protection of infants against meningococcal disease...

..These results suggest that MBL could modify disease susceptibility by modulating macrophage interactions with mucosal organisms at the site of initial acquisition...

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..These findings have implications for future therapeutic strategies against meningococcal disease on the basis of the blockade of TLRs and the modulation of LPS activity...

..pneumoniae releases proinflammatory cell-wall components that activate TLR2 and that this activity is dependent on autolysin, the growth phase of the organism, and the antibiotic concentration...

..They also allow us to distinguish between the various products that may be generated when NO reacts with molecules in complex biological samples such as cell lysates and supernatants...

..The aims of this study were to compare the DNA methylation status of the IL6 promoter in rheumatoid arthritis (RA) patients and control subjects and to study the effects on gene expression...

..This response in vivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae...

..This effect was dose-dependent. This work demonstrates that MBL is present in human semen and modifies cellular responses to N. gonorrhoeae in a concentration-dependent manner...

..Natural immunity to Neisseria meningitidis may result from nasopharyngeal carriage of closely related commensals, such as Neisseria lactamica...

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..We conclude that CHIPS is likely to be too immunogenic to be used as an anti-inflammatory treatment but that some antibodies against CHIPS may be useful in the treatment of S. aureus infections...

..Genetically determined variation in proinflammatory cytokine release influences severity of meningococcal disease and other serious infections...

..To systematically review evidence relating to the clinical efficacy of oseltamivir, zanamivir and amantadine in the prevention of influenza...

..A dynamic interaction between live intracellular bacteria and the host cell is necessary for induction of apoptosis in MDMs, and induction of apoptosis contributes to the host defense against S. pneumoniae...

..018; OR, 7.78 [95% CI, 1. 05-59.05]). There was no association between TNF genotype and fatal outcome. These data suggest that IL-1 genotype influences the severity of meningococcal disease...

..The lower levels of FtsH protease activity then influence sigma32, DnaK and, ultimately, FliC production...

..This defect is manifested as an impaired B-cell response to T-cell-independent type 2 antigens analogous to bacterial capsular polysaccharide...

..The implications of our findings for the understanding of genetic associations with disease susceptibility in this region are discussed...

..In the presence of influenza virus infection, these proteins were gradually lost over the course of 72 h. In conclusion, influenza B virus did not increase association of serogroup B N. meningitidis with human nasopharyngeal mucosa...

..Drugs that modify TNF in vivo may be a useful component of future management of sepsis, either as monotherapy or as part of a combined strategy of immunomodulation...

..The extent of previous exposure to pneumococcal capsular polysaccharide vaccination prior to an episode of IPD in hospitalised adults in the United Kingdom is unclear...

..Pattern recognition of bacterial superantigens by MHC class II receptors may exacerbate the proinflammatory response of monocytes to Gram-negative infection or endotoxin by up-regulation of TLR4...

..Expression of these genes by N. meningitidis during colonization and disease may confer protection against exogenous or endogenous nitrosative stress...

..This is consistent with the unpredictable epidemiology of meningococcal disease...

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..Studies with other strains defective for the uptake of specific nutrients should provide valuable information about the environment in which N. meningitidis persists during carriage...

..meningitidis...

..meningitidis retains considerable activity aerobically...